GLOSSARY

ABO blood-group antigen
Antigenic determinants of the blood-group system defined by the agglutination of red blood cells exposed to anti-A and anti-B antibodies.
Abzyme
A monoclonal antibody that has catalytic activity.
Acquired immunity
See adaptive immunity.
Acquired immunodeficiency syndrome (AIDS)
A disease caused by human immunodeficiency virus (HIV) that is marked by significant depletion of CD4+ T cells and that results in increased susceptibility to a variety of opportunistic infections and cancers.
Activation-induced cytidine deaminase (AID)
An enzyme that removes an amino group from deoxycytidine, forming deoxyuridine. This is the first step in the processes of both somatic hypermutation and class switch recombination.
Active immunity
Adaptive immunity that is induced by natural exposure to a pathogen or by vaccination.
Acute lymphocytic leukemia (ALL)
A form of cancer in which there is uncontrolled proliferation of a cell of the lymphoid lineage. The proliferating cells usually are present in the blood.
Acute myelogenous leukemia (AML)
A form of cancer in which there is uncontrolled proliferation of a cell of the myeloid lineage. The proliferating cells usually are present in the blood.
Acute phase protein
One of a group of serum proteins that increase in concentration in response to inflammation. Some complement components and interferons are acute phase proteins.
Acute phase response (APR)
The production of certain proteins that appear in the blood shortly after many infections, often induced by proinflammatory cytokines generated at the site of infection. It is part of the host’s early innate response to infection.
Acute phase response proteins
Proteins synthesized in the liver in response to inflammation; serum concentrations of these proteins increase in inflammation.
Acute rejection
Refers to the process of allo- or xenograft recognition and rejection that occurs after hyperacute rejection and that involves the action of both activated T and B cells. This stage of rejection can begin as early as 7 days after engraftment (following sensitization and effector cell engagement) and can continue for a year or more. This stage is usually amenable to control via immunosuppressive therapy.
Adapter Proteins
Proteins that connect to other effector proteins in a signaling pathway and create a signaling scaffold.
Adaptive immunity
Host defenses that are mediated by B cells and T cells following exposure to antigen and that exhibit specificity, diversity, memory, and self-nonself discrimination. See also innate immunity.
Addressin
A cell-surface protein or set of cell-surface proteins that are ligands for specific homing receptors on immune cells; they help guide immune cell trafficking.
Adenosine deaminase w(ADA) deficiency
An immune deficiency disorder that is characterized by defects in adaptive immunity and is caused by the intracellular accumulation of toxic adenosine metabolites, especially in hematopoietic cells, which interferes with purine metabolism and DNA synthesis.
Adhesion molecules
Families of surface proteins that regulate cell interactions with tissues, vessels, and with each other; they are important players in immune cell trafficking.
Adjuvant cancer therapy
A supplement or secondary treatment for cancer applied after the primary treatment (typically, surgical removal), which can include radiation and/or chemical/drug therapy meant to target residual tumor cells.
Adjuvants
Factors that are added to a vaccine mixture to enhance the immune response to antigen by activating innate immune cells. Dead mycobacterium were among the original adjuvants, but more refined preparation include alum, cytokines, and/or lipids.
Adoptive transfer
The transfer of the ability to make or participate in an immune response by the transplantation of cells of the immune system.
Affinity
The strength with which a monovalent ligand interacts with a binding site. It is represented quantitatively by the affinity constant Ka.
Affinity constant
The ratio of the forward (k1) to the reverse (k−1) rate constant in an antibody-antigen reaction. Equivalent to the association constant in biochemical terms (Ka = k1/k−1).
Affinity model of selection
A proposal stating that the fate of a developing T cell depends on the affinity of the interaction between its T cell receptor (TCR) and MHC-peptide ligand(s) it encounters in the thymus. High affinity interactions result in death by negative selection, lower affinity interactions in positive selection and maturation, and very low or no affinity interactions result in death by neglect.
Affinity maturation
The increase in average antibody affinity for an antigen that occurs during the course of an immune response or in subsequent exposures to the same antigen.
Agammaglobulinemia
Lack of immunoglobulin in the blood, causing immunodeficiency.
Agent-induced immunodeficiency
A state of immune deficiency induced by exposure to an environmental agent/s.
Agglutination inhibition
The reduction of antibody-mediated clumping of particles by the addition of the soluble forms of the epitope recognized by the agglutinating antibody.
Agglutination
The aggregation or clumping of particles (e.g., latex beads) or cells (e.g., red blood cells).
Agglutinin
A substance capable of mediating the clumping of cells or particles; in particular, a hemagglutinin (HA) causes clumping of red blood cells.
Agglutinin titer
The reciprocal of the greatest serum dilution that elicits a positive agglutination reaction.
AIM2-like receptors (ALRs)
Cytosolic receptors that bind DNA from bacteria and viruses. They are characterized by the presence of one or two HIN (hematopoietic expression, interferon inducibility, nuclear localization) domains at their carboxyl terminus.
AIRE
A protein that regulates expression of tissue specific antigens in the thymus. It is expressed by a subset of medullary epithelial cells and regulates transcription.
Alarmins
A diverse group of molecules, released in response to cellular stress, that summon protective inflammatory responses. Members of the IL-1 family of cytokines, including IL-33, are alarmins that are particularly important in regulating barrier immunity; they are released by damaged epithelial cells and help organize an immune response to the damaging pathogen.
Alleles
Two or more alternative forms of a gene at a particular locus that confer alternative characters. The presence of multiple alleles results in polymorphism.
Allelic exclusion
A process that permits expression of only one of the allelic forms of a gene. For example, a B cell expresses only one allele for an antibody heavy chain and one allele for a light chain.
Allergy
A hypersensitivity reaction that can include hay fever, asthma, serum sickness, systemic anaphylaxis, or contact dermatitis.
Allogeneic
Denoting members of the same species that differ genetically.
Allograft
A tissue transplant between allogeneic individuals.
Alloreactivity
Immunologic reactions directed against the nonself MHC molecules of another member of the same species. Up to 10% of circulating T cells are thought to have the ability to recognize foreign MHC within a species.
Allotypes
A set of allotypic determinants characteristic of some but not all members of a species.
Allotypic determinant
An antigenic determinant that varies among members of a species or between different inbred strains of animals. The constant regions of antibodies possess allotypic determinants.
Allotypic marker
A genetic marker that defines the presence of an allele on one strain of mouse that is not shared by other strains. Normally refers to allelic variants of immunoglobulin heavy chains.
Alpha-feto protein (AFP)
See oncofetal tumor antigen.
Altered peptide model
A proposal stating that developing T cells encounter different sets of peptides in the cortical region versus the medullary region of the thymus. Advanced to help explain differences in the subsets of cells that undergo positive versus negative selection.
Alternative pathway of complement activation
A pathway of complement activation that is initiated by spontaneous hydrolysis of the C3 component of complement, resulting in the formation of a fluid-phase C3 convertase enzyme. This spontaneous initiation distinguishes the alternative pathway from the classical and lectin-mediated pathways that are both initiated by specific antigen binding by either antibodies or lectins respectively. However, one recently-discovered branch of the alternative pathway may begin with Properdin binding to the surface of bacteria from the Neisseria genus.
Alternative tickover pathway
The alternative pathway of complement activation that is initiated by spontaneous hydrolysis of C3 molecule in the serum.
Alveolar macrophages (dust cells)
Macrophages found in the alveoli of the lung.
Alveoli
The clusters of sacs at the end of the bronchiolar branches where gas exchange takes place; alveoli are lined by a single layer of epithelial cells and are in contact with capillaries.
Amphiregulin
A protein factor, produced by epithelial cells as well as several types of immune cells, which contributes to tolerance and promotes healthy epithelial barriers; in the skin, amphiregulin helps promote keratinocyte proliferation.
Anaphylactic shock
An acute, life threatening (Type I) whole-body allergic response to an antigen (e.g. drugs, insect venom). See also Anaphylaxis.
Anaphylatoxins
The complement split products C3a and C5a, which mediate degranulation of mast cells and basophils, resulting in release of mediators that induce contraction of smooth muscle and increased vascular permeability.
Anaphylaxis
An immediate type I hypersensitivity reaction, which is triggered by IgE-mediated mast cell. Systemic anaphylaxis leads to shock and is often fatal. Localized anaphylaxis involves various types of atopic reactions.
Anchor residues
The amino acid residues at key locations in a peptide sequence that fit into pockets of an make close molecular associations with complementary amino acids in the groove of an MHC molecule and which help to determine the peptide-binding specificity of particular MHC molecules.
Anergic, anergy
Unresponsive to antigenic stimulus.
Antagonist, antagonize
A molecule that inhibits the effect of another molecule.
Anti-allotype antibodies
Antibodies directed towards allotypic determinants.
Anti-Fab antibodies
Antibodies directed towards the Fab regions of other antibodies.
Anti-Fc antibodies
Antibodies specific for the Fc regions of other antibodies.
Anti-idiotypic antibodies
Antibodies directed towards antigenic determinants located in the antigen binding site of other antibodies.
Anti-isotype antibodies
Antibodies directed towards antigenic determinants located in the constant regions of antibodies, that are shared among all members of a species.
Anti-oncogenes
Another name for tumor suppressor genes.
Antibodies
Immunoglobulin proteins consisting of two identical heavy chains and two identical light chains, that recognize a particular epitope on an antigen and facilitates clearance of that antigen. Membrane-bound antibody is expressed by B cells that have not encountered antigen; secreted antibody is produced by plasma cells. Some antibodies are multiples of the basic four-chain structure.
Antibody molecule
See antibodies.
Antibody-dependent cell-mediated cytotoxicity (ADCC)
A cell-mediated reaction in which nonspecific cytotoxic cells that express Fc receptors (e.g., NK cells, neutrophils, macrophages) recognize bound antibody on a target cell and subsequently cause lysis of the target cell.
Antibody-dependent cellular phagocytosis (ADCP)
Phagocytosis of antigens opsonized by antibodies.
Antigen
Any substance (usually foreign) that binds specifically to an antibody or a T-cell receptor; often is used as a synonym for immunogen.
Antigen presentation
See antigen processing.
Antigen processing
Degradation of antigens by one of two pathways yielding antigenic peptides that are displayed bound to MHC molecules on the surface of antigen-presenting cells or altered self cells.
Antigen-presenting cell (APC)
Any cell that can process and present antigenic peptides in association with MHC class II molecules and deliver a costimulatory signal necessary for T-cell activation. Macrophages, dendritic cells, and B cells constitute the professional APCs. Nonprofessional APCs, which function in antigen presentation only for short periods include thymic epithelial cells and vascular endothelial cells.
Antigenic determinant
The site on an antigen that is recognized and bound by a particular antibody, TCR/MHC-peptide complex, or TCR-ligand-CD1 complex; also called epitope.
Antigenic drift
A series of spontaneous point mutations that generate minor antigenic variations in pathogens and lead to strain differences. See also Antigenic shift.
Antigenic peptide
In general, a peptide capable of raising an immune response, for example, in a peptide that forms a complex with MHC that can be recognized by a T-cell receptor.
Antigenic shift
Sudden emergence of a new pathogen subtype, frequently arising due to genetic reassortment that has led to substantial antigenic differences. See also Antigenic drift.
Antigenic specificity
See specificity, antigenic.
Antigenically committed
The state of a mature B cell displaying surface antibody specific for a single immunogen.
Antigenicity
The capacity to combine specifically with antibodies or T-cell receptor/MHC.
Antimicrobial peptides
Peptides/small proteins, such as defensins, less than 100-amino acids long that are produced constitutively or after activation by pathogens.
Antimicrobial proteins
Enzymes and other proteins that directly damage pathogens, induce phagocytosis, or inhibit pathogen infectivity or replication.
Antiretroviral therapy (ART)
Treatment with drugs that inhibit the replication of HIV.
Antiserum
Serum from animals immunized with antigen that contains antibodies to that antigen.
Apical surface
The portion of the membrane of an epithelial cell that faces the lumen of a tissue.
Apoptosis
A process, often referred to as programmed cell death, where cells initiate a signaling pathway that results in their own demise. Apoptosis requires ATP and is typically dependent on the activation of internal caspases. In contrast to necrosis, it does not result in damage to surrounding cells.
Apoptosome
A wheel-like assemblage of molecules that regulate cell death initiated via the mitochondrial (intrinsic) pathway. Includes cytochrome-c, ATP, Apaf-1, and caspase-9.
APRIL
A member of the Tumor Necrosis Factor family of cytokines, important in B cell development and homeostasis.
Artemis
An enzyme that is a member of the Non-homologous End Joining (NHEJ) DNA repair pathway. During V(D)J recombination, Artemis opens the hairpin loops formed after RAG1/2-mediate cleavage of the immunoglobulin genes.
Association constant (Ka)
See affinity constant.
Atopic
Pertaining to clinical manifestations of type I (IgE-mediated) hypersensitivity, including allergic rhinitis (hay fever), eczema, asthma, and various food allergies.
Atopic (allergic) march
The natural history or typical progression of allergic diseases that often begin early in life, starting with atopic dermatitis (eczema) and progressing to food allergy, allergic rhinitis (hay fever), and possibly asthma.
Atopy
The genetic tendency to develop allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis (eczema); typically associated with heightened immune responses to common allergens, especially inhaled and food allergens.
Attenuate
To decrease the virulence of a pathogen and render it incapable of causing disease. Many vaccines are composed of attenuated bacteria or viruses that induce protective immunity without causing harmful infection.
Autocrine
A type of cell signaling in which the cell acted on by a cytokine is the source of the cytokine.
Autograft
Tissue grafted from one part of the body to another in the same individual.
Autoimmune diseases
A group of disorders caused by the action of ones own antibodies or T cells reactive against self proteins.
Autoimmune polyendocrine syndrome type 1 (APS-1)
An immune deficiency disorder in which depressed expression of AIRE results in reduced levels of tissue-specific antigens in thymic epithelial cells, allowing the escape of autoreactive T cells into the periphery, where they precipitate organ-specific autoimmunity.
Autoimmune polyendrocrinopathy and ectodermal dystrophy (APECD)
An immune deficiency disorder in which depressed expression of Aire results in reduced levels of tissue-specific antigens in thymic epithelial cells, allowing the escape of autoreactive T cells into the periphery, where they precipitate organ-specific autoimmunity.
Autoimmunity
An abnormal immune response against self antigens.
Autologous
Denoting transplanted cells, tissues, or organs derived from the same individual.
Autophagosome
Membrane-bound vesicle formed by autophagy.
Autophagy
Elimination of intracellular pathogens and organelles by envelopment by intracellular membranes and fusion of resulting autophagosomes with lysosomes.
Avidity
The strength of antigen-antibody binding when multiple epitopes on an antigen interact with multiple binding sites of an antibody. See also affinity.
B cell
See B lymphocytes.
B lymphocytes (B cells)
Lymphocytes that mature in the bone marrow and express membrane-bound antibodies. After interacting with antigen, they differentiate into antibody-secreting plasma cells and memory cells.
B-1 B cells
A subclass of B cells that predominates in the peritoneal and pleural cavity. B-1 B cells in general secrete low affinity IgM antibodies and do not undergo class switch recombination or somatic hypermutation. They thus occupy a niche between the innate and adaptive immune responses. Most, but not all, B-1 B cells express CD5 on their surface.
B-1b B cells
A subclass of B-1 cells that does not express the antigen CD5 on its cell surface, like most B-1 B cells.
B-2 B cells
The predominant class of B cells that are stimulated by antigens with T cell help the generate antibodies of multiple heavy chain classes whose genes undergo somatic hypermutation.
B-cell coreceptor
A complex of three proteins (CR2 (CD21), CD19, and TAPA-1) associated with the B-cell receptor. It is thought to amplify the activating signal induced by cross-linkage of the receptor.
B-cell receptor (BCR)
Complex comprising a membrane-bound immunoglobulin molecule and two associated signal-transducing Iga/Igb molecules.
B-cell-specific activator protein (BSAP)
A transcription factor encoded by the gene Pax-5 that plays an essential role in early and later stages of B-cell development.
B-lymphocyte-induced maturation protein 1 (BLIMP-1)
Transcription factor vital to differentiation of B cells into plasma cells.
Bacillus Calmette-Guérin (BCG)
An attenuated form of Mycobacterium bovis used as a vaccine against another member of the genus, M. tuberculosis, the cause of tuberculosis. BCG can also be found as an adjuvant component in other vaccines.
Bacteremia
An infection in which viable bacteria are found in the blood.
BAFF
B-cell survival factor; a membrane-bound homolog of tumor necrosis factor, to which mature B cells bind though the TACI receptor. This interaction activates important transcription factors that promote B-cell survival, maturation, and antibody secretion.
BAFF receptor (BAFF-R)
Receptor for BAFF, a cytokine belonging to the tumor necrosis factor family that is important in B cell development and homeostasis.
Balanced signals model
Model for how NK cell killing is targeted at virus-infected, stressed, or tumor cells. The balance of signals from NK inhibitory and activating receptors determines whether the NK cell will induce apoptosis in the target cells.
Bare-lymphocyte syndrome (BLS)
An immunodeficiency syndrome in which, without MHC class II molecules, positive selection of CD4+ T cells in the thymus is impaired and, with it, peripheral T helper cell responses.
Barrier immunity
The system of immune cells, tissues, and responses that protects barrier tissues from damage and infection.
Barrier organs
Tissues lined by epithelial cells, which are directly exposed to the external environment; includes the gastrointestinal, respiratory, reproductive, and urinary tracts, as well as the skin.
Barrier tissues
Tissues and organs that form protective boundaries between the external and internal environments of a body; include skin and the mucosal tissues (gastrointestinal, respiratory, reproductive, urogenital tracts) as well as distinct immune cells and systems.
Basolateral surface
The portion of the membrane of an epithelial cell that faces the mucosal layer of a tissue (and is oriented away from the lumen).
Basophil
A nonphagocytic granulocyte that expresses Fc receptors for IgE. Antigen-mediated cross-linkage of bound IgE induces degranulation of basophils.
BCG
See Bacillus Calmette-Guérin.
Bence-Jones proteins
Monoclonal light chains secreted by plasmacytoma tumors. Found in high concentrations in the urine of patients with multiple myeloma.
Benign
Pertaining to a nonmalignant form of a neoplasm or a mild form of an illness.
β-selection
The process during the DN3 stage of T cell development where the functionality of thymocytes’ rearranged TCRb chains is tested. Only those thymocytes that have successfully rearranged a TCRb chain and expressed it as a protein that can interact with pre-TCRa will deliver signals that ensure its survival, maturation to the CD4+CD8+ (DP) stage, and induce its proliferation.
β2-microglobulin
Invariant subunit that associates with the polymorphic a chain to form MHC class I molecules; it is not encoded by MHC genes.
Bispecific antibody
Hybrid antibody made either by chemically cross-linking two different antibodies or by fusing hybridomas that produce different monoclonal antibodies.
Bone marrow
The living tissue found within the hard exterior of bone.
Booster
Inoculation given to stimulate and strengthen an immunologic memory response.
Bradykinin
An endogenously produced peptide that produces an inflammatory response.
Bronchus-associated lymphoid tissue (BALT)
Secondary lymphoid microenvironments in the lung mucosa system that support the development of the T and B lymphocyte response to antigens that enter the lower respiratory tract. Part of the mucosa associated lymphoid tissue system (MALT).
C (constant) gene segment
The 39 coding of a rearranged immunoglobulin or T-cell receptor gene. There are multiple C gene segments in germ-line DNA, but as a result of gene rearrangement and, in some cases, RNA processing, only one segment is expressed in a given protein.
c-Kit (CD117)
Receptor for stem cell factor (SCF).
C-reactive protein (CRP)
An acute phase protein that binds to phosphocholine in bacterial membranes and functions in opsonization; an increased level of serum CRP is an indicator of inflammation.
C-type lectin receptor (CLR)
A family of pattern-recognition receptors that contains C-type lectin carbohydrate-binding domains.
C3 convertase
Enzyme that breaks down the C3 component of complement into C3a and C3b.
C3aR
A cell-surface receptor for the complement component and anaphylatoxin C3a.
C5 convertase
Enzyme that breaks down the C5 component of complement into C5a and C5b.
C5aR and C5L2
Cell-surface receptors for the complement component and anaphylatoxin C5a.
Calnexin
A protein resident of the ER that serves, along with calreticulin, as a molecular chaperone to assist in MHC class I molecule assembly.
Calreticulin
A protein resident of the ER that serves, along with calnexin, as a molecular chaperone to assist in MHC class 1 molecule assembly.
Cancer stem cells
A subset of cells within a tumor that has the stem-cell-like ability to give rise to all cells within that tumor and the ability to self-renew indefinitely. They are thought to be responsible for tumor growth.
CAR T cells
See chimeric antigen receptor T cells.
Carcinoembryonic antigen (CEA)
An oncofetal antigen (found not only on cancerous cells but also on normal cells) that can be a tumor-associated antigen.
Carcinogen
Any chemical substances, physical agents or types of radiation that can induce DNA mutations and lead to the development of cancer.
Carcinoma
Tumor arising from endodermal or ectodermal tissues (e.g., skin or epithelium). Most cancers (.80%) are carcinomas.
Carrier
An immunogenic molecule containing antigenic determinants recognized by T cells. Conjugation of a carrier to a nonimmunogenic hapten renders the hapten immunogenic.
Carrier effect
A secondary immune response to a hapten depends on use of both the hapten and the carrier used in the initial immunization.
Cascade induction
The property of cytokines that pertains to their ability to induce one cell to release cytokines that then act upon another to induce the release of other cytokines and growth factors.
Caspase
A family of cysteine proteases that cleave after an aspartate residue. The term caspase incorporates these elements (cysteine, aspartate, protease), which play important roles in the chain of reactions that leads to apoptosis.
Caspase recruitment domains (CARD)
Protein domain that binds caspase proteases.
Cathelicidin
A type of antimicrobial peptide secreted by epithelial cells and found in lysosomes of phagocytic cells; it disrupts pathogen membranes and has other toxic effects.
CC subgroup
A subgroup of chemokines in which a disulfide bond links adjacent cysteines.
CD19
A quintessential B-cell marker, often used as such in flow cytometry experiments.
CD21
The B cell co-receptor molecule that also serves as a co-receptor for the complement components C3d and C3dg. Also known as CR2.
CD25
The high affinity IL-2 receptor chain (IL-2a) expressed on the surface of multiple immune cells, including some developing T cells, activated T cells, and many FoxP3+ T cells.
CD28
A costimulatory receptor that cooperates with the TCR to activate naïve T cells; binding to CD80 and CD86 ligands results in an increase in IL-2 expression.
CD3
A polypeptide complex containing three dimers: a ϓε heterodimer, a εd heterodimer, and either a jj homodimer or a jh heterodimer. It is associated with the T-cell receptor and functions in signal transduction.
CD4
A glycoprotein that serves as a co-receptor on MHC class II–restricted T cells. Most helper T cells are CD4+.
CD40
Member of the tumor necrosis factor receptor family. Signaling through CD40L on T cells to CD40 on B cells is necessary for germinal center formation, somatic hypermutation and class switch recombination.
CD40L
Ligand for CD40. CD40L is a member of the Tumor Necrosis Factor family of molecules and CD40 a member of the TNF receptor family. CD40:CD40L interactions are indispensable during T cell mediated B cell differentiation. B cells bear CD40 and T cell, CD40L.
CD44
Surface protein involved in cell-cell adhesion that is expressed by multiple immune cells, including some developing T cells, and some activated T cells. Differences in CD44 and CD25 expression distinguish very early stages of T cell development. CD44 is also associated with immune cell activation.
CD5 antigen
An antigen found on most B-1 B cells, (B-1a B cells), as well as on many T cells.
CD59
Regulatory protein that binds to and inhibits the membrane attack complex of complement.
CD8
A dimeric protein that serves as a co-receptor on MHC class I–restricted T cells. Most cytotoxic T cells are CD8+.
CD80/86
Molecules whose expression on the cell surfaces of antigen-presenting cells and B cells is up-regulated when the cells take up and process antigen. They serve as ligands for the T-cell-surface molecule CD28.
CDR3
The third complementarity-determining region, (or hypervariable region) of the immunoglobulin or TCR molecules.
Cell adhesion molecules (CAMs)
A group of cell surface molecules that mediate intercellular adhesion. Most belong to one of four protein families: the integrins, selectins, mucin-like proteins, and immunoglobulin superfamily.
Cell line
A population of cultured tumor cells or normal cells that have been subjected to chemical or viral transformation. Cell lines can be propagated indefinitely in culture.
Cell-mediated immune response
Host defenses that are mediated by antigen-specific T cells. It protects against intracellular bacteria, viruses, and cancer and is responsible for graft rejection. Transfer of primed T cells confers this type of immunity on the recipient. See also humoral immune response.
Cell-mediated immunity
See cell-mediated immune response.
Cell-mediated lympholysis (CML)
In vitro lysis of allogeneic cells or virus-infected syngeneic cells by T cells; can be used as an assay for CTL activity or MHC class I activity.
Cellular innate immune responses
Cell responses activated by binding of conserved pathogen components to cell-surface or intracellular receptors.
Cellular oncogene
See proto-oncogene.
Central memory T cells (TCM)
A memory T cell subset that localizes to and resides in secondary lymphoid tissue. It participates in the secondary response to antigen and can give rise to new effector T cells. TCM may arise from effector T cells and/or from T cells that have been stimulated towards the end of an immune response.
Central tolerance
Elimination of self-reactive lymphocytes in primary generative organs such as the bone marrow and the thymus (see also peripheral tolerance).
Centroblasts
Rapidly dividing B cells that have recognized antigen, migrated into the follicles, and formed a germinal center. Centroblasts reside in the dark zone of the germinal center.
Centrocytes
B cells that have recognized antigen and migrated into the follicles, where they undergo somatic hypermutation followed by antigen-induced selection. Centrocytes are located in the light zone of the germinal center.
cGAS
Cyclic GMP-AMP synthase. A cytosolic pattern recognition receptor that recognizes cytosolic DNA, usually of bacterial or viral origin, and generates dinucleotides that activate STING.
Checkpoint blockade
In immunotherapy, any of a number of cancer treatments that employ immune checkpoint inhibitors to prevent inhibitory signaling in T cells, theoretically releasing these T cells to mount anti-tumor cell responses.
Checkpoint inhibitors
Anticancer drugs usually in the form of monoclonal antibodies that interfere with co-inhibitory signaling (checkpoints) in the activation of T cell responses, such as via CTLA-4 or PD-1.
Chediak-Higashi syndrome
An autosomal recessive immune deficiency disorder caused by a defect in lysosomal granules that impairs killing by NK cells.
Chemical barriers
Tissue layer that provides innate immune protection against infection by chemical means, such as low pH and presence of degradative enzymes.
Chemoattractant
A substance that attracts cells. Some chemoattractants also cause significant changes in the physiology of cells that bear receptors for them.
Chemokine receptors
Surface proteins expressed by immune cells that guide their migration among tissues and localization within tissues. They generate signals that regulate motility and adhesion when bound to chemokines secreted by a variety of immune and stromal cells.
Chemokines
Any of several secreted low-molecular-weight cytokines that mediate chemotaxis in particular leukocytes via receptor engagement and that can regulate the expression and/or adhesiveness of leukocyte integrins (see Appendix III).
Chemotactic factor
An agent that can cause leukocytes to move up its concentration gradient.
Chemotaxis
The induction of cell movement by the secretion of factors that either attract or repel the cell through the mediation of receptors for those factors.
Chimera
An animal or tissue composed of elements derived from genetically distinct individuals. The SCID-human mouse is a chimera. Also, a chimeric antibody that contains the amino acid sequence of one species in one region and the sequence of a different species in another (for example, an antibody with a human constant region and a mouse variable region).
Chimeric antibody
See chimera.
Chimeric antigen receptor T
(CAR T) cells T cells that have been modified to encode a gene for a composite antigen-specific receptor that is a fusion of BCR sequences recognizing a target antigen (H and L chain variable regions) with TCR-specific sequences (CD3 and sometimes costimulatory domains), allowing the T cell to recognize and kill tumor cells expressing the antigen without the requirement for MHC presentation.
Chromogenic substrate
A colorless substance that is transformed into colored products by an enzymatic reaction.
Chronic granulomatous disease
Immunodeficiency caused by a defect in the enzyme NADPH (phagosome) oxidase resulting in failure to generate reactive oxygen species in neutrophils.
Chronic inflammation
Inflammation that may have a rapid or slow onset but is characterized primarily by its persistence and lack of clear resolution; it occurs when the tissues are unable to overcome the effects of the injuring agent; it involves a progressive change in the types of cells present at the site of inflammation.
Chronic lymphocytic leukemia (CLL)
A type of leukemia in which cancerous lymphocytes are continually produced.
Chronic myelogenous leukemia (CML)
A type of leukemia in which cancerous lymphocytes of the myeloid lineage are continually produced.
Chronic rejection
Transplant/graft rejection reactions that begin months or years after engraftment and can sometimes continue or recur for the lifetime of the patient. The effector cells and molecules are the same as those involved in acute rejection; however, this stage is more difficult to treat and accounts for most of the incidents of graft failure after the initial weeks and months post transfer.
Cilia
Hairlike projections on cells, including epithelial cells in the respiratory and gastrointestinal tracts; cilia function to propel mucus with trapped microbes out of the tract.
Class (isotype) switching
The change in the antibody class that a B cell produces.
Class 1 cytokines
The largest of the cytokine families, typified by Interleukin 2 (IL-2).
Class I MHC genes
See MHC class I genes.
Class I MHC molecules
See MHC class I molecules.
Class II MHC genes
See MHC class II genes.
Class II MHC molecules
See MHC class II molecules.
Class III MHC genes
See MHC class III genes.
Class III MHC molecules
See MHC class III molecules.
Class switch recombination (CSR)
The generation of antibody genes for heavy chain isotypes other than m or d by DNA recombination.
Class
The property of an antibody that is defined by the nature of its heavy chain (μ, δ, γ, α, or ε).
Classical MHC molecules
A set of highly polymorphic surface proteins encoded in the major histocompatibility locus that are characterized by an alpha and beta chain which binds peptide for presentation to classical a/b T cells (CD4+ or CD8+) and essential for activation of adaptive responses. Examples of classical Class I molecules include HLA-A, –B and –C (human) or H2-D, –L and –K (mouse). Class II examples include HLA-DP, –DQ and –DR (human) or H2-A and –E (mouse).
Classical pathway of complement activation
That pathway of complement activation that is initiated by antibody binding to antigen.
CLIP
A protein that binds to the groove of MHC class II as it is assembled and carried to the cell surface. It prevents other peptides from associating with MHC class II until it encounters endocytosed proteins, when CLIP is digested and removed from the groove.
Clonal anergy
A physiological state in which cells are unable to be activated by antigen.
Clonal deletion
The induced death of members of a clone of lymphocytes with inappropriate receptors (e.g., those that strongly react with self during development).
Clonal selection hypothesis
This hypothesis states that antigen interacting with a receptor on a lymphocyte induces division and differentiation of that lymphocyte to form a clone of identical daughter cells. All daughter cells will bear the same receptor as the stimulated cell, and antibodies produced by B cells stimulated in this way will share the antigen-binding site with the membrane receptor of the stimulated cell. Following antigen elimination, representatives of the stimulated clone remain in the host as a source of immunological memory. Those clones of B cells that meet antigen at an immature stage of development will be eliminated from the repertoire.
Clonal selection
The antigen-mediated activation and proliferation of members of a clone of B cells that have receptors for the antigen (or for complexes of MHC and peptides derived from the antigen, in the case of T cells).
Clone
Cells arising from a single progenitor cell.
Clot
Coagulated mass; usually refers to coagulated blood, in which conversion of fibrinogen in the plasma to fibrin has produced a jelly-like substance containing entrapped blood cells.
Cluster of differentiation (CD)
A collection of monoclonal antibodies that all recognize an antigen found on a particular differentiated cell type or types. Each of the antigens recognized by such a collection of antibodies is called a CD marker and is assigned a unique identifying number.
Coding joints
The nucleotide sequences at the point of union of coding sequences during V(D)J rearrangement to form rearranged antibody or T-cell receptor genes.
Codominant
The expression of both the maternal and the paternal copy of a gene in a heterozygote.
Coinhibitory receptors
Receptors expressed on the surface of some T cells that send signals that inhibit T cell activation. CTLA-4 is a common negative costimulatory molecule that is expressed on some activated T cells and helps to downregulate immune responses when antigen is cleared.
Collectins
Family of calcium-dependent carbohydrate-binding proteins containing collagen-like domains.
Combined immunodeficiencies (CID)
Any of a number of immune deficiency disorders resulting from an absence of T cells or significantly impaired T-cell function, combined with some disruption of antibody responses.
Commensal microbiome
The diverse community of microbes (bacteria, viruses, fungi, and worms) that coexist with our barrier tissues without causing damage; commensal microbes provide diverse benefits to barrier tissues.
Common lymphoid progenitor (CLP)
An immature blood cell that develops from the hematopoietic stem cell and gives rise to lymphocytes, including B and T cells and NK cells.
Common myeloid-erythroid progenitor (CMP)
An immature blood cell that develops from the hematopoietic stem cell and gives rise to all red blood cells and myeloid cells, including monocytes, macrophages, and granulocytes.
Complement
A group of serum and cell membrane proteins that interact with one another and with other molecules of innate and adaptive immunity to carry out key effector functions leading to pathogen recognition and elimination.
Complement system
See complement.
Complementarity-determining region (CDR)
Portions of the variable regions of antibody molecules that contain the antigen-binding residues.
Confocal microscopy
A type of fluorescence microscopy that, like two-photon microscopy, allows one to image fluorescent signals within one focal plane within a relatively thick tissue sample.
Conformational determinants
Epitopes of a protein that are composed of amino acids that are close together in the three-dimensional structure of the protein but may not be near each other in the amino acid sequence.
Congenic
Denoting individuals that differ genetically at a single genetic locus or region; also called coisogenic.
Constant (C) region
The nearly invariant portion of the immunoglobulin molecule that does not contain antigen-binding domains. The sequence of amino acids in the constant region determines the isotype (α, γ, δ, ε, and μ) of heavy chains and the type (k and l) of light chains.
Constant (CL)
That part of the light chain that is not variable in sequence.
Contraction
The final phase in the immune response after infection has been cleared and the number of responsive lymphocytes decreases via apoptosis.
Coreceptor
A cell-surface molecule that is noncovalently associated with an antigen receptor, and that binds to molecules on antigen-presenting cells that are associated either covalently or noncovalently with the antigen or antigen-associated molecules.
Correlates of immune protection
Specific immunologic effector memory responses, such as neutralizing antibodies or epitope-specific CTLs, that recognize particular structures present in/on an infectious agent and that when present will protect the individual against subsequent infection or disease from infection with that same organism.
Cortex
The outer or peripheral layer of an organ.
Cortical thymic epithelial cells (cTECs)
Stromal cells of epithelial origin that populate the cortex of the thymus and mediate positive selection of thymocytes.
Costimulatory receptors
Receptors expressed on the surface of T cells that deliver one of two signals required for T cell activation (Signal 2). They are activated when engaged by ligands, which are typically expressed by professional APC. The most common costimulator receptor is CD28.
Costimulatory signal
Additional signal that is required to induce proliferation of antigen-primed T cells and is generated by interaction of CD28 on T cells with CD80/86 on antigen-presenting cells. In B-cell activation, an analogous signal is provided by interaction of CD40 on B cells with CD40L on activated TH cells.
CR1
Complement Receptor 1. Expressed on both erythrocytes and leukocytes and binds to C3b, C4b and their breakdown products. CR1 expression on erythrocytes is important in the clearance of immune complexes in the liver.
CR3
A cell-surface receptor for complement component iC3b and factor H.
CR4
A cell-surface receptor for complement component iC3b.
CRIg
A cell-surface receptor for complement components C3b, iC3b, and C3c.
Crohn’s disease
A form of inflammatory bowel disease (IBD) that can afflict any part of the intestine and is characterized by accumulation of inflammatory cells and granuloma formation, which interferes with digestion.
Cross-matching
Refers to pretransplantation testing of the serum of the recipient for any preexisting antibodies capable of recognizing the allogeneic MHC molecules of a potential donor. Even when the recipient has never before received a transplant, most will have some antibodies capable of recognizing allogenic MHC molecules, most likely due to our regular exposure to food and microbes expressing cross-reactive epitopes.
Cross-presentation
A protein processing and presentation pathway that occurs in some pAPCs where antigen acquired by endocytosis is redirected from the exogenous to the endogenous pathway, such that peptides associate with MHC class I molecules for presentation to CD8+ T cells.
Cross-priming
The activation of CTL responses to antigens processed and presented via cross-presentation.
Cross-reactivity
Ability of a particular antibody or T-cell receptor to react with two or more antigens that possess a common epitope.
Cross-tolerance
The induction of CD8+ T cell tolerance to an antigen processed and presented via cross-presentation.
Cryptopatches
Small aggregates of lymphoid cells found in the intestinal wall that are precursors of isolated lymphoid follicles (ILFs).
Crypts
The epithelial cell–lined valleys between the villi of the gastrointestinal tract; these are lined by specialized epithelial cells and include the stem cells that continually replenish the epithelial lining of the intestine.
CTLA-4 (CD152)
A coinhibitory receptor that blocks T-cell activation, acting as a checkpoint that down-regulates immune responses; up-regulated by T cells after activation.
CTL precursors (CTL-Ps)
Naïve CD8+ T cells that have not yet been activated by antigen recognition. They do not yet express the cytotoxic machinery associated with fully mature killer T cells.
CXC subgroup
A family of chemokines that contain a disulfide bridge between cysteines separated by a different amino acid residue (X).
Cyclooxygenase 2 (COX2)
Enzyme responsible for the formation from arachidonic acid of prostaglandins and other pro-inflammatory mediators; target of non-steroidal anti-inflammatory drugs.
Cyclosporin A
A fungal product used as a drug to suppress allograft rejection. The compound blocks T-cell activation by interfering with transcription factors and preventing gene activation.
Cytokine storms
The pathological secretion of extremely high levels of cytokines induced by massive infection with particular pathogens. Typical symptoms include increased capillary permeability with resultant loss of blood pressure and shock, sometimes leading to death.
Cytokine-binding Homology Region (CHR)
A protein motif common to the cytokine binding receptors of several families.
Cytokines
Any of numerous secreted, low-molecular-weight proteins that regulate the intensity and duration of the immune response by exerting a variety of effects on lymphocytes and other immune cells that express the appropriate receptor (see Appendix II).
Cytosolic pathway
See Endogenous pathway.
Cytotoxic natural killer (NK) cells
A subset of ILCs within the ILC1 category that have cytotoxic rather than helper potential.
Cytotoxic T lymphocytes (CTLs, or Tc cells)
An effector T cell (usually CD8+) that can mediate the lysis of target cells bearing antigenic peptides complexed with a MHC class I molecule.
Damage-associated molecular patterns (DAMPs)
Components of dead/dying cells and damaged tissues that are recognized by pattern-recognition receptors.
Danger or damage model
A model of immune response theory which posits that the immune response distinguishes between dangerous and nondangerous structures rather than the classical view of differentiation between self and nonself structures.
Dark zone
A portion of the germinal center that is the site of rapid cell division by forms of B cells called centroblasts.
Death by neglect
Apoptosis of developing T cells (typically CD4+CD8+ thymocytes) that results when they do not receive TCR signals of adequate affinity. Most (90% or more) developing T cells undergo death by neglect.
Death domains
Protein motifs found in the cytoplasmic region of Fas and other proapoptotic signaling molecules. They engage the domains on other signaling molecules and initiate the formation of the Death-Inducing Signaling Complex (DISC).
Death-Inducing Signaling Complex (DISC)
An intracellular signaling aggregate formed in response to engagement of death receptors, including Fas. It includes the cytoplasmic tail of Fas, FADD, and procaspase-8, and initiates apoptosis.
Defensins
Antimicrobial peptides (AMPs) generated by many cell types, including some T cells, epithelial cells of barrier tissue, and other innate immune cells; defensins can compromise bacteria, fungi, and certain viruses.
Degranulation
Discharge of the contents of cytoplasmic granules by basophils and mast cells following cross-linkage (usually by antigen) of bound IgE. It is characteristic of type I hypersensitivity.
Delayed-type hypersensitivity (DTH)
A type IV hypersensitive response mediated by sensitized TH cells, which release various cytokines and chemokines. The response generally occurs 2 to 3 days after TH cells interact with antigen. It is an important part of host defense against intracellular parasites and bacteria.
Dendritic cells (DCs)
Bone-marrow-derived cells that descend through the myeloid and lymphoid lineages and are specialized for antigen presentation to helper T cells.
Dermis
Layer of skin under the epidermis that contains blood and lymph vessels, hair follicles, nerves, and nerve endings.
Desensitization
Reduction in allergic responses achieved by repeated low or increasing doses of allergens administered through injections of allergens (allergy shots), sublingual application (under the tongue), and oral immunotherapy (feeding the allergen).
Determinant-selection model
A hypothesis proposed to explain the variability in immune responsiveness to different MHC haplotypes. This model states that each MHC molecule binds a unique array of antigenic peptides, and some peptides are more successful in eliciting an effective immune response than others. See also Holes-in-the-repertoire model.
Diacylglyerol (DAG)
A lipid molecule generated upon cleavage of phosphatidyl inositol bisphosphate that is important in cell signaling.
Diapedesis
The process by which a cell crosses from the lumen of a vessel, between endothelial cells, and into the surrounding tissue.
Differentiation antigen
A cell surface marker that is expressed only during a particular developmental stage or by a particular cell lineage.
DiGeorge syndrome (DGS)
Congenital thymic aplasia (partial or total absence of the thymus) caused by deletion of a sequence on chromosome 22 during embryonic life. Consequences include immunodeficiency, facial abnormalities, and congenital heart disease.
Direct staining
A variation of fluorescent antibody staining in which the primary antibody is directly conjugated to the fluorescent label.
Dissociation constant
Kᵠ, the reciprocal of the association constant (1/Ka).
Diversity (D) segment
One of the gene segments encoding the immunoglobulin heavy chain or the TCR ᵝ or ᵟ chains or its protein product.
DN1
The first in the four stages in the development of the most immature (CD4-CD8- or double negative) thymocytes. DN1 cells express CD44 but not CD25 and are the progenitors that come from the bone marrow and have the potential to give rise to multiple lymphoid and myeloid cell lineages.
DN2
The second in the four stages in the development of the most immature (CD4-CD8- or double negative) thymocytes. Commitment to the T cell lineage and rearrangement of the first TCR receptor genes occur among DN2 cells, which express both CD44 and CD25.
DN3
The third in the four stages in the development of the most immature (CD4-CD8- or double negative) thymocytes. Only those DN3 cells that express a functional TCRb chain continue to mature to the CD4+CD8+ stage and proliferate (β-selection). DN3 cells express CD25, but not CD44.
DN4
The last of the four stages in the development of the most immature (CD4-CD8- or double negative) thymocytes. DN4 cells express neither CD44 nor CD25 and are in transition to the CD4+CD8+ (double positive or DP) stage of development.
Double immunodiffusion
A type of precipitation in gel analysis in which both antigen and antibody diffuse radially from wells toward each other, thereby establishing a concentration gradient. As equivalence is reached, a visible line of precipitation, a precipitin line, forms.
Double-negative (DN) cells
A subset of developing T cells (thymocytes) that do not express CD4 or CD8. At this early stage of T-cell development, DN cells do not express the TCR.
Double-positive (DP) stage
A subset of developing T cells (thymocytes) that express both CD4 and CD8. DP cells are an intermediate stage of developing thymocytes that express TCRs.
Downstream
(1) Towards the 39 end of a gene; (2) Further away from the receptor in a signaling cascade.
Duodenum
A section of the small intestine; the duodenum is short and the site of secretion of digestive enzymes.
Dynamic imaging
An approach and set of techniques that allows the visualization of living cells in living tissue.
Dysbiosis
An alteration in the microbiome that negatively affects the balance of microbial communities typically found in healthy, commensal communities of microbes.
E2A
A transcription factor that is required for the expression of the recombination-activating genes (RAG) as well as the expression of the ʎ5 (lambda 5) component of the pre-B-cell receptor during B-cell development. It is essential for B-cell development.
Early B-cell factor 1 (EBF1)
Key transcription factor at the common lymphoid progenitor stage of B-cell development. It is induced by E2A, Foxo1, Runx1, and signals through the IL-7R.
Early lymphoid progenitor cell (ELP)
A progenitor cell capable of dividing to give rise to either T or B lymphocyte progenitors.
Edema
Abnormal accumulation of fluid in intercellular spaces, often resulting from a failure of the lymphatic system to drain off normal leakage from the capillaries.
Effector caspases
The subset of caspase enzymes directly responsible for the cell apoptosis. Their cleavage activity results both in the breakdown of structural molecules (e.g. actin) or the activation of destructive molecules (e.g. endonucleases). Caspase-3 and caspase-7 are two well-characterized effector caspases.
Effector cell
Any cell capable of mediating an immune function (e.g., activated TH cells, CTLs, and plasma cells).
Effector cytokines
Cytokines released by effector lymphocytes, including helper T-cell subsets and cytotoxic T cells, that regulate the immune response to pathogens.
Effector memory T cells (TEM)
A memory T cell subset that circulates among or resides in peripheral, non-lymphoid tissue. It is generated during the primary response and participates in the secondary response to antigen, exhibiting effector functions and proliferating more quickly than immune cells.
Effector phase
The stage of immune activity when effector cells work to resolve pathogen infection at barrier tissues; preceded by the inductive phase.
Effector response
Immune cell action that contributes to the clearance of infection. It includes responses mediated by helper T cells, which secrete cytokines that enhance the activity of several other immune cell subsets, by cytotoxic cells, including CD8+ T cells and NK cells, and by antibody, which recruits soluble proteins (complement) and cells that can kill and clear pathogen. Also called effector function.
ELISA
See enzyme-linked immunosorbent assay.
Embryonic stem (ES) cell
Stem cell isolated from early embryo and grown in culture. Mouse ES cells give rise to a variety of cell types and are used to develop transgenic or knockout mouse strains.
Endocrine
Referring to regulatory secretions such as hormones or cytokines that pass from producer cell to target cell by the bloodstream.
Endocytosis
Process by which cells ingest extracellular macromolecules by enclosing them in a small portion of the plasma membrane, which invaginates and is pinched off to form an intracellular vesicle containing the ingested material.
Endogenous pathway
Intracellular route taken by antigen that is processed for presentation by MHC class I, typically associated with proteins generated in the cytosol.
Endosteal niche
Microenvironment in the bone marrow that fosters the development of hematopoietic stem cells and is postulated to associate specifically with self-renewing, long-term hematopoietic stem cells.
Endotoxins
Certain lipopolysaccharide (LPS) components of the cell wall of gram-negative bacteria that are responsible for many of the pathogenic effects associated with these organisms. Some function as superantigens.
Enterocyte
The absorptive epithelial cell that lines the small intestine; these cells are polarized with an apical surface folded into microvilli that faces the lumen of the intestine and a basolateral surface that faces the intestinal wall. They are responsible for absorbing food, but also play an active role in protecting the epithelial layer from infection.
Enzyme-linked immunosorbent assay (ELISA)
An assay for quantitating either antibody or antigen by use of an enzyme-linked antibody and a substrate that forms a colored reaction product.
Eosinophils
Motile, somewhat phagocytic granulocytes that can migrate from blood to tissue spaces. They have large numbers of IgE receptors and are highly granular. They are thought to play a role in the defense against parasitic organisms such as roundworms.
Epidermis
The outermost layer of the skin.
Epigenetic
Describes modifications to genes other than changes in the DNA sequence that affect gene expression; examples include chromatin modifications such as histone methylation.
Epitope mapping
Localization of sites (epitopes) on an antigen molecule that are reactive with different antibodies or T-cell receptors.
Epitope
The portion of an antigen that is recognized and bound by an antibody or TCR-MHC combination; also called antigenic determinant.
Equilibrium dialysis
An experimental technique that can be used to determine the affinity of an antibody for antigen and its valency.
ERAP
Endoplasmic reticulum aminopeptidase. An enzyme responsible for trimming amino acids from peptides in the ER in order to reach an optimal length for binding to MHC class I molecules.
Erythroblastosis fetalis
A type II hypersensitivity reaction in which maternal antibodies against fetal Rh antigens cause hemolysis of the erythrocytes of a newborn; also called hemolytic disease of the newborn.
Erythrocytes
Red blood cells.
Exocytosis
Process by which cells release molecules (e.g., cytokines, lytic enzymes, degradation products) contained within a membrane-bound vesicle by fusion of the vesicle with the plasma membrane.
Exogenous pathway
Intracellular route taken by antigen that is processed for presentation by MHC class II, typically associate with proteins that are endocytosed.
Exotoxins
Toxic proteins secreted by gram-positive and gram-negative bacteria; some function as superantigens. They cause food poisoning, toxic shock syndrome, and other disease states. See also immunotoxin.
Extravasation
Movement of blood cells through an unruptured blood vessel wall into the surrounding tissue, particularly at sites of inflammation.
F (ab´)2 fragment
Two Fab units linked by disulfide bridges between fragments of the heavy chain. They are obtained by digestion of antibody with pepsin.
Fab (fragment antigen binding) region
Region at the N-terminus of the antibody molecule that interact with antigen. This antibody fragment, consisting of one light chain and part of one heavy chain, linked by an interchain disulfide bond, is obtained by brief papain digestion.
Factor B
A protein component of the alternative pathway of complement activation that is cleaved by factor D.
Factor D
An enzyme of the alternative pathway of complement activation that cleaves factor B into Ba and Bb only when it is bound to either C3(H2O) or to C3b.
Fas (CD95)
A member of the Tumor Necrosis Factor Receptor family. On binding to its ligand, FasL, the Fas-bearing cell will often be induced to commit to an apoptotic program. Occasionally, however, Fas ligation leads to cell proliferation.
Fas ligand (FasL)
FasL is a member of the Tumor Necrosis Factor family of molecules and interacts with the Fas receptor, which is a member of the Tumor Necrosis Factor Receptor family. Signals delivered from FasL to Fas usually result in the death by apoptosis of the Fas-bearing cell.
Fc (fragment crystallizable) region
Region at the C terminus of the antibody molecule that interacts with Fc receptors on other cells and with components of the complement system. This crystallizable antibody fragment consists of the carboxyl-terminal portions of both heavy chains and is obtained by brief papain digestion.
Fc receptor (FcR)
Cell-surface receptor specific for the Fc portion of certain classes of immunoglobulin. It is present on lymphocytes, mast cells, macrophages, and other accessory cells.
FcεRI receptor
The high-affinity receptor for the Fc of IgE that induces degranulation of mast cells, basophils, and eosinophils.
FcεRII (CD23) receptor
The low-affinity receptor for IgE. Regulates B-cell activation, growth, and IgE synthesis; triggers transport of IgE and IgE/food allergen complexes across the intestinal epithelium; activates macrophages to release TNF, IL-1, IL-6, and GM-CSF.
FcᵞRIIb
A receptor that binds to the Fc region of antibodies engaged in antigen:antibody complexes. Signals through this receptor down-regulate B cell division and differentiation.
Fibrin
A filamentous protein produced by the action of thrombin on fibrinogen; fibrin is the main element in blood clotting.
Fibrinopeptide
One of two small peptides of about 20 amino acids released from fibrinogen by thrombin cleavage in the conversion to fibrin.
Fibroblast reticular cells (FRCs)
Stromal cells in secondary lymphoid tissue (and at some immune response sites in the periphery) that extend processes which provide the surface networks on which dendritic cells position themselves and T and B lymphocytes migrate as they probe for antigen. Associated with chemokines and cytokines that help guide cell movements.
Fibrosis
A process responsible for the development of a type of scar tissue at the site of chronic inflammation.
Ficolin
Member of a family of carbohydrate-binding proteins that contain a fibrinogen-like domain and a collagen-like domain.
Flow cytometer
An instrument that users lasers along with sophisticated optics to measure multiple fluorescent and light scattering parameters from thousands of cells as flow rapidly, one-by-one in front of the laser beam.
Fluorescence Activated Cell Sorter (FACS)
A flow cytometer equipped with the ability to sort cells sharing particular fluorescence and light scattering properties into different containers.
Fluorescence microscopy
A microscopic technique that allows the visualization of fluorescent signals generated from cells tagged with fluorescent antibodies or proteins.
Fluorescent antibody
An antibody with a fluorochrome conjugated to its Fc region that is used to stain cell surface molecules or tissues; the technique is called immunofluorescence.
Fluorochrome
A molecule that fluoresces when excited with appropriate wavelengths of light. See immunofluorescence.
fms-related tyrosine kinase 3 receptor (flt-3)
Binds to the membrane-bound flt-3 ligand on bone marrow stromal cells and signals the progenitor cell to begin synthesizing the IL-7 receptor.
Follicles
Microenvironments that specifically support the development of the B lymphocyte response in lymph nodes, spleen, and other secondary lymphoid tissue. They also become the site of development of the germinal center when a B cell is successfully activated.
Follicular dendritic cell (FDC)
A cell with extensive dendritic extensions that is found in the follicles of lymph nodes. Although they do not express MHC class II molecules, they are richly endowed with receptors for complement and Fc receptors for antibody. They are of a lineage that is distinct from MHC class II–bearing dendritic cells.
Follicular helper T (TFH) cells
Helper CD4+ T cell subset that supports the development of B lymphocytes in the follicle and germinal center and expresses the master transcriptional regulator Bcl-6.
Follicular mantle zone
Zone of naïve, IgD-bearing B cells that surrounds the central region of a follicle engaged in a germinal center reaction. The non-antigen-specific, IgD-bearing cells are slowly pushed to the outside of the follicle as they are displaced by dividing cells in the germinal center.
Foxo1
Transcription factor important in B-cell development. It is induced by E2A and contributes to the activation of EBF1.
Fragmentin
Enzymes present in the granules of cytotoxic lymphocytes that induce DNA fragmentation.
Framework region (FR)
A relatively conserved sequence of amino acids located on either side of the hypervariable regions in the variable domains of immunoglobulin heavy and light chains.
Freund’s complete adjuvant (CFA)
A water-in-oil emulsion to which heat-killed mycobacteria have been added; antigens are administered in CFA to enhance their immunogenicity.
Freund’s incomplete adjuvant
Freund’s adjuvant lacking heat-killed mycobacteria.
G-Protein–Coupled Receptors (GPCRs)
Ligand receptors that interact with G proteins on the cytoplasmic side of the plasma membrane. G proteins are signal-transducing molecules that are activated when the receptor binds to its ligand. Receptor:ligand binding induces a conformational change in the G protein that induces it to exchange the GDP (which is in its binding site in the resting state), for GTP. The activated G protein:GTP complex then transduces the signal. GPCRs have a shared structure in which the proteins passes through the member a total of seven times.
ᵞ(gamma)-globulin fraction
ϓ The electrophoretic fraction of serum that contains most of the immunoglobulin classes.
Gastrointestinal (GI) tract
A mucosal tissue that is part of the barrier organ system; the GI tract, or gut, is responsible for digesting and distributing food, cultivating beneficial relationships with the commensal microbiome, and protecting the body from infection. It includes the mouth, esophagus, stomach, small intestine (duodenum, jejunum, ileum), and large intestine (colon). All of the intestinal tract except the mouth is lined by a single layer of epithelial cells.
GATA-2 gene
A gene encoding a transcription factor that is essential for the development of several hematopoietic cell lineages, including the lymphoid, erythroid, and myeloid lineages.
Gene conversion
Process in which portions of one gene (the recipient) are changed to those of another gene (the donor). Homologous gene conversion is a diversification mechanism used for immunoglobulin V≈genes in some species.
Gene segments
Germ-line gene sequences that are combined with others to make a complete coding sequence; Ig and TCR genes are products of V, D, J gene segments.
Gene therapy
General term for any measure aimed at correction of a genetic defect by introduction of a normal gene or genes.
Generation of diversity
The generation of a diverse repertoire of antigen-binding receptors on B or T lymphocytes that occurs in the bone marrow or thymus, respectively.
Genome wide sequence
The sequence of all DNA (the entire genome) present in a cell.
Genotype
The combined genetic material inherited from both parents; also, the alleles present at one or more specific loci.
Germ-line theories
Classical theories that attempted to explain antibody diversity by postulating that all antibodies are encoded in the host chromosomes.
Germinal centers (GCs)
A region within lymph nodes and the spleen where T-dependent B-cell activation, proliferation, and differentiation occur. Germinal centers are sites of intense B-cell somatic mutation and selection.
Goblet cells
Specialized cells in the epithelium that lines mucosal tissues; they are responsible for secreting mucus and are particularly abundant in the large intestine but are present in all mucosal tissues.
Graft-versus-host (GVH) reaction
A pathologic response to tissue transplantation in which immune cells in the transplanted tissue (graft) react against and damage host cells.
Graft-versus-host disease (GVHD)
A reaction that develops when a graft contains immunocompetent T cells that recognize and attack the recipient’s cells.
Granulocytes
Any leukocyte that contains cytoplasmic granules, particularly the basophil, eosinophil, and neutrophil.
Granuloma
A tumor-like mass or nodule that arises because of a chronic inflammatory response and contains many activated macrophages, TH cells, and multinucleated giant cells formed by the fusion of macrophages.
Granzyme (fragmentin)
One of a set of enzymes found in the granules of TC cells that can help to initiate apoptosis in target cells.
Grave’s disease
An autoimmune disease in which the individual produces auto-antibodies to the receptor for thyroid-stimulating hormone TSH.
GTP-binding proteins
Proteins that bind Guanosine Tri-phosphate.
GTPase Activating Proteins (GAPs)
G proteins have an intrinsic GTPase activity that serves to limit the time during which G proteins can actively transduce a signal. GAPs enhance this GTPase activity, and thus further limit the signal through a GPCR.
Guanine-nucleotide Exchange Factors (GEFs)
Small proteins that catalyze the exchange of GTP for GDP in the guanine nucleotide binding sites of small and trimeric G proteins.
Gut-associated lymphoid tissue (GALT)
Secondary lymphoid microenvironments in the intestinal (gut) system that support the development of the T and B lymphocyte response to antigens that enter gut mucosa. Part of the mucosa associated lymphoid tissue system (MALT).
H2 complex
Term for the MHC in the mouse.
HAART
See Highly active antiretroviral therapy.
Haplotype
The set of alleles of linked genes present on one parental chromosome; commonly used in reference to the MHC genes.
Hapten
A low-molecular-weight molecule that can be made immunogenic by conjugation to a suitable carrier.
Hapten-carrier conjugate
A covalent combination of a small molecule (hapten) with a large carrier molecule or structure.
Heavy (H) chain
The larger polypeptide of an antibody molecule; it is composed of one variable domain VH and three or four constant domains (CH1, CH2, etc.) There are five major classes of heavy chains in humans (α, ϖ, δ, ε, and μ), which determine the isotype of an antibody.
Heavy-chain Joining segment (JH)
One of the gene segments encoding the immunoglobulin heavy chain or its protein product.
Heavy-chain Variable region
That part of the immunoglobulin heavy chain protein that varies from antibody to antibody and is encoded by the V, D, and J gene segments.
Heavy-chain Variable segment (VH)
(1) One of the gene segments encoding the immunoglobulin heavy chain gene, or its protein product.
Helper T (TH) cells
See T helper (TH) cells.
Hemagglutination
The process of sticking together red blood cells using multivalent cells, viruses or molecules that bind to molecules on the red blood cell surface. Viruses such as influenza or antibodies are routinely measured by hemagglutination assays.
Hemagglutinin (HA)
Any substance that causes red blood cells to clump, or agglutinate. Most commonly the virally-derived glycoprotein found on the surface of influenza virus that binds to sialic acid residues on host cells causing them to agglutinate. See also agglutinin.
Hematopoiesis
The formation and differentiation of blood cells.
Hematopoietic stem cell (HSC)
The cell type from which all lineages of blood cells arise.
Hemolysis
Alteration or destruction of red blood cells, which liberates hemoglobin.
Heptamer
A conserved set of 7 nucleotides contiguous to each of the V, D, and J gene segments of all immunoglobulin and TCR gene segments. It serves as the recognition signal and binding site of the RAG1/2 protein complex.
Herd immunity
When the majority of the population is immune to an infectious agent, thus significantly reducing the pathogen reservoir due to the low chance of a susceptible individual contacting an infected individual.
Heteroconjugates
Hybrids of two different antibody molecules.
Heterotypic
An interaction between two molecules where the interacting domains have different structures from one another.
High-endothelial venule (HEV)
An area of a capillary venule composed of specialized cells with a plump, cuboidal (“high”) shape through which lymphocytes migrate to enter various lymphoid organs.
Highly active antiretroviral therapy (HAART)
A form of drug therapy used to treat infection with HIV that utilizes a combination of three or more anti-HIV drugs from different classes to inhibit viral replication and avoid selection of drug-resistant mutants.
Hinge
The flexible region of an immunoglobulin heavy chain between the CH1 and CH2 domains that allows the two binding sites to move independently of one another.
Histamine
A small mediator released during degranulation of mast cells, basophils, and eosinophils that causes symptoms of allergic reactions, including vasodilation, increased vascular permeability, mucus secretion, and smooth muscle contraction.
Histiocyte
An immobilized (sometimes called “tissue fixed”) macrophage found in loose connective tissue.
Histocompatibility antigens
Family of proteins that determines the ability of one individual to accept tissue or cell grafts from another. The major histocompatibility antigens, which are encoded by the MHC, function in antigen presentation.
Histocompatible
Denoting individuals whose major histocompatibility antigens are identical. Grafts between such individuals are generally accepted.
HLA (human leukocyte antigen) complex
Term for the MHC in humans.
Holes-in-the-repertoire model
The concept that immune tolerance results from the absence of receptors specific for self antigens.
Homeostasis, homeostatic
Pertaining to processes that contribute to the maintenance and stability of a system, in this case, the immune system, under normal conditions.
Homing receptor
A receptor that directs various populations of lymphocytes to particular lymphoid and inflammatory tissues.
Homing
The differential migration of lymphocytes or other leukocytes to particular tissues or organs.
Homotypic
An interaction between two molecules where the interacting domains have identical or very similar structures to one another.
Human immunodeficiency virus (HIV)
The retrovirus that causes acquired immune deficiency syndrome (AIDS).
Human leukocyte antigen (HLA) complex
See HLA complex.
Humanized antibody
An antibody that contains the antigen-binding amino acid sequences of another species within the framework of a human immunoglobulin sequence.
Humoral immune response
Host defenses that are mediated by antibody present in the plasma, lymph, and tissue fluids. It protects against extracellular bacteria and foreign macromolecules. Transfer of antibodies confers this type of immunity on the recipient. See also cell-mediated immune response.
Humoral immunity
See humoral immune response.
Humoral
Pertaining to extracellular fluid, including the plasma, lymph, and tissue fluids.
Hybridoma
A clone of hybrid cells formed by fusion of normal lymphocytes with myeloma cells; it retains the properties of the normal cell to produce antibodies or T-cell receptors but exhibits the immortal growth characteristic of myeloma cells. Hybridomas are used to produce monoclonal antibody.
Hygiene hypothesis
Hypothesis that a lack of early childhood exposure to infectious agents, certain symbiotic microorganisms (such as the gut flora or probiotics), and parasites increases susceptibility to allergic diseases by suppressing the natural development of some components of the immune system.
Hyper IgE syndrome (HIE)
An immune deficiency syndrome characterized by over expression of IgE and most frequently caused by mutations in the gene encoding STAT3. Also known as Job syndrome.
Hyper IgM syndrome (HIM)
An immune deficiency disorder that arises from inherited deficiencies in CD40L, resulting in impaired T cell-APC communication and a lack of isotype switching, manifesting as elevated levels of IgM but an absence of other antibody isotypes.
Hyperacute rejection
The earliest of the stages of graft rejection, occurring within minutes or hours of transfer; it involves the action of preformed antibodies that can recognize antigens (usually MHC molecules) on the engrafted organ/tissue/cells.
Hypersensitivity
Exaggerated immune response that causes damage to the individual. Immediate hypersensitivity (types I, II, and III) is mediated by antibody or immune complexes, and delayed-type hypersensitivity (type IV) is mediated by TH cells.
Hypervariable
Those parts of the variable regions of the BCR and TCR that exhibit the most sequence variability and interact with the antigen. Otherwise known as the complementarity determining regions.
Hypogammaglobulinemia
Any immune deficiency disorder, either inherited or acquired, characterized by low levels of gammaglobulin (IgG).
Iccosomes
Immune-complex-coated cell fragments often found coating the spines of follicular dendritic cells.
Idiotope
A single antigenic determinant in the variable domains of an antibody or T-cell receptor; also called idiotypic determinant. Idiotopes are generated by the unique amino acid sequence specific for each antigen.
Idiotype
The set of antigenic determinants (idiotopes) characterizing a unique antibody or T-cell receptor.
IgD
Immunoglobulin D. An antibody class that serves importantly as a receptor on naïve B cells.
IgM
Immunoglobulin M. An antibody class that serves as a receptor on naïve B cells. IgM is also the first class of antibody to be secreted during the course of an immune response. Secreted IgM exists primarily in pentameric form.
Ikaros
A transcription factor required for the development of all lymphoid cell lineages.
IKK
See IkB kinase.
IKK α
IkB kinase α subunit.
IKK β
IkB kinase β subunit.
IL-1 Receptor Activated Kinase (IRAK)
A family of kinases that participates in the signaling pathway from IL-1. IRAKs are also important in TLR signaling.
IL-2
A cytokine produced by activated T cells that promotes T-cell division in both autocrine and paracrine fashions.
IL-10
A member of the interferon family of cytokines, that usually mediates an immuno-suppressive effect.
IL-17 family
A family of cytokines implicated in the early stages of the immune response. Most members of this family are pro-inflammatory in action.
IL-23–TH17 cell axis
A cytokine/T-cell system that regulates inflammation and is responsible for several immune-mediated and inflammatory diseases; IL-23 induces differentiation of TH17 and ILC3 subsets, both of which can produce several potent proinflammatory cytokines, including IL-17, IL-22, and GM-CSF.
IL-7 receptor
Receptor for the cytokine Interleukin 7, which is important for lymphocyte development.
Ileum
A section of the small intestine; the jejunum and ileum are responsible for final digestion and absorption of food.
Immature B cell
Immature B cells express a fully-formed IgM receptor on their cell surface. Contact with antigen at this stage of B cell development results in tolerance induction rather than activation. Immature B cells express lower levels of IgD and higher levels of IgM than do mature B cells. They also have lower levels of anti-apoptotic molecules and higher levels of Fas than mature B cells, reflective of their short-half lives.
Immature B-cell (second) checkpoint
Developing B cells are tested at the immature B cell stage to determine whether they successfully rearranged both heavy chain and light chain genes and can express an IgM B-cell receptor. Those B cells that fail to express a BCR are eliminated by apoptosis and are referred to as having failed to pass through the immature B-cell checkpoint.
Immediate hypersensitivity
An exaggerated immune response mediated by antibody (type I and II) or antigen-antibody complexes (type III) that manifests within minutes to hours after exposure of a sensitized individual to antigen.
Immune complex
A complex of antibody with bound antigen.
Immune deficiency
See immunodeficiency.
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
An inherited immune deficiency disorder that manifests as an autoimmune syndrome caused by a lack of FoxP3 expression and near absence of regulatory T cells (TREG cells).
Immune imbalance
A bias of the immune response toward overly robust immune activity (or occasionally, underactivity) that is nontypical and nonspecific, most often manifesting as a generalized decrease in the immuno-inhibitory elements of immune recognition of self and/or benign foreign antigens.
Immune responsiveness
The ability of an organism to respond to a particular antigen in a manner that leads to an adaptive immune response. Immune responsiveness is determined by the genes within the MHC locus, especially class II, and is based on the affinity of MHC molecules for the antigen in question.
Immunity
A state of protection from a particular infectious disease.
Immunization
The process of producing a state of immunity in a subject. See also active immunity and passive immunity.
Immunocompetent
Denoting a mature lymphocyte that is capable of recognizing a specific antigen and mediating an immune response; also an individual without any immune deficiency.
Immunodeficiency
Any deficiency in the immune response, whether inherited or acquired. It can result from defects in phagocytosis, humoral immunity, cell-mediated responses, or some combination of these.
Immunodominant
Referring to epitopes that produce a more pronounced immune response than others under the same conditions.
Immunoediting
A recently formulated theory concerning the role of the immune system in responding to cancer. It includes three phases (elimination, equilibrium, and escape) and incorporates both positive (anti-tumor) and negative (pro-tumor) processes mediated by the immune system in responding to malignancy.
Immunoelectron microscopy
A technique in which antibodies used to stain a cell or tissue are labeled with an electron-dense material and visualized with an electron microscope.
Immunoelectrophoresis
A technique in which an antigen mixture is first separated into its component parts by electrophoresis and then tested by double immunodiffusion.
Immunofluorescence
Technique of staining cells or tissues with fluorescent antibody and visualizing them under a fluorescent microscope.
Immunogen
A substance capable of eliciting an immune response. All immunogens are antigens, but some antigens (e.g., haptens) are not immunogens.
Immunogenicity
The capacity of a substance to induce an immune response under a given set of conditions.
Immunoglobulin (Ig)
Protein consisting of two identical heavy chains and two identical light chains, that recognize a particular epitope on an antigen and facilitates clearance of that antigen. There are 5 types: IgA, IgD, IgE, IgG, and IgM. Also called antibody.
Immunoglobulin domains
Three dimensional structures characteristic of immunoglobulin and related proteins including T cell receptors, MHC proteins and adhesion molecules. Consists of a domain of 100 – 110 amino acids folded into two β -pleated sheets, each containing three of four antiparallel b strands and stabilized by an intrachain disulfide bond.
Immunoglobulin fold
Characteristic structure in immunoglobulins that consists of a domain of 100 to 110 amino acids folded into two β-pleated sheets, each containing three or four antiparallel β strands and stabilized by an intrachain disulfide bond.
Immunoglobulin superfamily
Group of proteins that contain immunoglobulin-fold domains, or structurally related domains; it includes immunoglobulins, T-cell receptors, MHC molecules, and numerous other membrane molecules.
Immunologic memory
The ability of the immune system to respond much more swiftly and with greater efficiency during a second, or later exposure to the same pathogen.
Immunomodulatory
Any compound or inducer that changes the behavior of immune cells. This is most often used to refer to the activity of costimulatory (e.g., CD28) or coinhibitory (e.g., CTLA-4) molecules but encompasses both categories more broadly.
Immunoproteasome
A variant of the standard 20S proteasome, found in pAPCs and infected cells, that has unique catalytic subunits specialized to produce peptides that bind efficiently to MHC class I proteins.
Immunoreceptor tyrosine-based inhibitory motif (ITIM)
An amino acid sequence containing tyrosine residues in conserved sequence relationships with one another that serves as a docking site for downstream signaling molecules that will send an inhibitory signal to the cell. More formally known as immuno-receptor tyrosine-based inhibitory motif.
Immunoreceptor tyrosine-based activation motif (ITAM)
Amino acid sequence in the intracellular portion of signal-transducing cell surface molecules that interacts with and activates intracellular kinases after ligand binding by the surface molecule.
Immunosurveillance
A theory concerning anti-cancer responses that is now part of the immunoediting hypothesis (elimination phase) which posits that cells of the immune system continually survey the body in order to recognize and eliminate tumor cells.
Immunotherapy
Any of a variety of medical therapies or drug treatments designed to revive, initiate, or supplement the ability of the existing immune response to target cancer cells for elimination.
Immunotoxin
Highly cytotoxic agents sometimes used in cancer treatment that are produced by conjugating an antibody (for instance, specific for tumor cells) with a highly toxic agent, such as a bacterial toxin.
Incomplete antibody
Antibody that binds antigen but does not induce agglutination.
Indirect staining
A method of immunofluorescent staining in which the primary antibody is unlabeled and is detected with an additional fluorochrome-labeled reagent.
Induced TREG (iTREG) cells
CD4+ T cell subset that negatively regulates immune responses and is induced to develop by specific cytokine interactions in secondary lymphoid tissue that upregulate the master regulator FoxP3.
Inducible costimulator (ICOS or CD278)
A costimulatory receptor that cooperates with the TCR to activate some T cells; it binds the ICOS ligand, which is known by several names including B7-H2.
Inducible nitric oxide synthetase (iNOS)
An inducible form of NOS that generates the antimicrobial compound nitric oxide from arginine.
Inflamed
Manifesting redness, pain, heat, and swelling. See also Inflammation.
Inflammasomes
Multiprotein complex that promotes inflammation by processing inactive precursor forms of pro-inflammatory cytokines such as IL-1 and IL-18.
Inflammation
Tissue response to infection or damage which serves to eliminate or wall-off the infection or damage; classic signs of acute inflammation are heat (calor), pain (dolor), redness (rubor), swelling (tumor), and loss of function.
Inflammatory bowel disease (IBD)
Chronic intestinal inflammation that can be subdivided into two types: Crohn’s disease and ulcerative colitis.
Inflammatory response
A localized tissue response to injury or other trauma characterized by pain, heat, redness, and swelling. The response includes both localized and systemic effects, consisting of altered patterns of blood flow, an influx of phagocytic and other immune cells, removal of foreign antigens, and healing of the damaged tissue.
Inductive phase
The stage of immune activity when the response to pathogens encountered in barrier tissues is initiated; followed by the effector phase.
Inhibitor of NF-κB (IκB)
A small protein that binds to the transcription factor NF-κB that inhibits its action, in part by retaining it in the cytoplasm.
Initiator caspases
The subset of caspase enzymes that initiate the process leading to cell apoptosis. Initiator caspases typically cleave and activate effector caspases, although they can also cleave other molecules that indirectly activate effector caspases (e.g. Bid). Caspase-8 is a well-characterized initiator caspase that is associated with the death receptor, Fas, and is cleaved and activated when Fas is engaged.
Innate immunity
Non-antigen specific host defenses that exist prior to exposure to an antigen and involve anatomic, physiologic, endocytic and phagocytic, anti-microbial, and inflammatory mechanisms, and which exhibit no adaptation or memory characteristics. See also adaptive immunity.
Innate immunity effect or mechanisms
Chemical and cellular mechanisms by which the innate immune system eliminates pathogens.
Innate lymphoid cells (ILCs)
Lymphocytes that lack antigen-specific B- and T-cell receptors and contribute to both innate and adaptive immune responses. Three subsets of ILCs (ILC1, ILC2, ILC3) are recognized, most of which share features with helper T-cell subsets (TH1, TH2, TH17, respectively).
Inositol trisphosphate (IP3)
A phosphorylated six-carbon sugar that binds to receptors in the membranes of the endoplasmic reticulum, leading to the release of Ca2+ ions into the cytoplasm.
Instructive model
A model advanced to explain the molecular basis for lineage commitment, the choice of a CD4+CD8+ thymocyte to become a CD4+ versus a CD8+ T cell. This model proposes that DP thymocytes that interact with MHC class II receive a distinct signal from DP thymoctyes that interact with MHC class I. These distinct signals induce differentiation into the helper CD4+ or the cytotoxic CD8+ lineage, respectively. This model is no longer accepted. See also Kinectic signaling model.
Insulin-dependent diabetes mellitus (IDDM)
An autoimmune disease caused by T cell attack on the insulin-producing beta cells of the pancreas, necessitating daily insulin injections.
Integrins
A group of heterodimeric cell adhesion molecules (e.g., LFA-1, VLA-4, and Mac-1) present on various leukocytes that bind to Ig-superfamily CAMs (e.g., ICAMs, VCAM-1) on endothelium.
Intercellular adhesion molecules (ICAMs)
Cellular adhesion molecules that bind to integrins. ICAMs are members of the immunoglobulin superfamily.
Interferon regulatory factor 4 (IRF-4)
Transcription factor important to the initiation of plasma cell differentiation.
Interferon regulatory factors (IRFs)
Transcription factors induced by signaling downstream of pattern-recognition, interferon, and other receptors that activate interferon genes.
Interferons (IFNs)
Several glycoprotein cytokines produced and secreted by certain cells that induce an antiviral state in other cells and also help to regulate the immune response.
Interleukin-1 (IL-1) family
Interleukin-1 was the first cytokine to be discovered. Members of this family interact with dimeric receptors to induce responses that are typically pro-inflammatory.
Interleukins (ILs)
A group of cytokines secreted by leukocytes that primarily affect the growth and differentiation of various hematopoietic and immune system cells (see Appendix II).
Interstitial fluid
Fluid found in the spaces between cells of an organ or tissue.
Intraepidermal lymphocytes
T cells found in epidermal layers.
Intraepithelial lymphocytes (IELs)
T cells found in the epithelial layer of organs and the gastrointestinal tract.
Intravital fluorescence microscopy
A type of microscopy that allows one to image cell activity within living tissue and live organisms.
Invariant (Ii) chain
Component of the MHC class II protein that shows no genetic polymorphism. The Ii chain stabilizes the class II molecule before it has acquired an antigenic peptide.
Invariant NKT (iNKT) cells
A cytotoxic T cell subset that develops in the thymus and expresses very limited TCRαβ receptor diversity (one specific TCRa paired with only a few TCRb chains) and recognize lipids associated with CD1, an MHC-like molecule.
IRAK1
See IL-1 receptor–activated kinase.
Isograft
Graft between genetically identical individuals.
Isolated lymphoid follicles (ILFs)
Dynamic secondary lymphoid tissue aggregates found in the wall of the small intestine that assemble and disassemble in response to antigen exposure; follicles in ILFs are key reservoirs of IgA-producing B cells.
Isotype
(1) An antibody class that is determined by the constant-region sequence of the heavy chain. The five human isotypes, designated IgA, IgD, IgE, IgG, and IgM, exhibit structural and functional differences. Also refers to the set of isotypic determinants that is carried by all members of a species. (2) One of the five major kinds of heavy chains in antibody molecules (α, γ, δ, ε, and μ).
Isotype switching
Conversion of one antibody class (isotype) to another resulting from the genetic rearrangement of heavy-chain constant-region genes in B cells; also called class switching.
Isotypic determinant
An antigenic determinant within the immunoglobulin constant regions that is characteristic of a species.
iTREG cells
A type of T cell that, following antigen exposure in the periphery, is induced to express FoxP3 and acquire regulatory functions, suppressing immune activity against specific antigen. See also nTREG cells.
IκB kinase (IKK)
The enzyme that phosphorylates the inhibitory subunit of the transcription factor NF-κB. Phosphorylation of IκB results in its release from the transcription factor and movement of the transcription factor into the nucleus.
J (joining) chain
A polypeptide that links the heavy chains of monomeric units of polymeric IgM and di- or trimeric IgA. The linkage is by disulfide bonds between the J chain and the carboxyl-terminal cysteines of IgM or IgA heavy chains.
J (joining) gene segment
The part of a rearranged immunoglobulin or T-cell receptor gene that joins the variable region to the constant region and encodes part of the hypervariable region. There are multiple J gene segments in germ-line DNA, but gene rearrangement leaves only one in each functional rearranged gene.
JAK
See Janus Activated Kinase.
Janus Activated Kinase (JAK)
Kinase that typically transduce a signal from a Type 1 or Type 2 cytokine receptor to a cytoplasmically-located transcription factor belonging to the STAT (Signal Transducer and Activator of Transcription) family. On cytokine binding to the receptor, the JAK kinases are activated and phosphorylate the receptor molecule. This provides docking sites for a pair of STAT molecules which are phosphorylated, dimerize, and translocate to the nucleus to effect their transcriptional programs.
Jejunum
A section of the small intestine; the jejunum and ileum are responsible for final digestion and absorption of food.
Job syndrome
See Hyper IgE syndrome.
Joining (J) segment
One of the gene segments encoding the immunoglobulin heavy or light chain or any of the four TCR chains or its protein product
Junctional flexibility
The diversity in antibody and T-cell receptor genes created by the imprecise joining of coding sequences during the assembly of the rearranged genes.
Kd
See dissociation constant
Kappa (κ) light chain
One of the two types of immunoglobulin light chains that join with heavy chains to form the B cell receptor and antibody heterodimer. Lambda (λ) is the other type.
Keratinocytes
Specialized epithelial cells of the skin that contribute to a many-layered epithelial barrier; they are part of the epidermis—the top layer of the skin.
Kinetic signaling model
A model advanced to explain the molecular basis for lineage commitment, the choice of a CD4+CD8+ thymocyte to become a CD4+ versus a CD8+ T cell. This model proposes that all DP thymocytes receiving T cell receptor signals decrease expression of CD8. Those thymocytes whose TCR binds MHC class II will continue to receive a signal stabilized by CD4-MHC class II interactions and will progress to the CD4+ lineage. However those thymocytes whose TCR binds MHC class I will have this signal disrupted by the reduction in stabilizing CD8-MHC class I interactions. These cells require rescuing by cytokines (IL-7 or IL-15) which promote their development to the CD8+ lineage.
KIR
Immunoglobulin-like receptors expressed by human natural killer cells that bind MHC class I molecules and inhibit cytotoxicity.
Knock-in genetics
A genetic manipulation that results in the insertion of a desired mutant form of a gene or a marker gene in a pre-selected site in the genome.
Knockout genetics
A genetic manipulation that results in the elimination of a selected gene from the genome.
Kupffer cell
A type of tissue-fixed macrophage found in liver.
λ5
A polypeptide that associates with Vpre-B to form the surrogate light chain of the pre-B-cell receptor.
Lambda (λ) chain
One of the two types of immunoglobulin light chains that join with heavy chains to form the B cell receptor and antibody heterodimer. Kappa (k) is the other type.
Lamina propia
Layer of loose connective tissue under the intestinal epithelium where immune cells are organized. The site of the GALT and part of the mucosal immune system.
Langerhans cells
Specialized, highly mobile antigen-presenting cells found specifically in the skin; Langerhans cells process antigen and travel from skin to lymph nodes, where they present antigen to naïve T cells.
Large pre-B cells
The stage in B-cell development at which the BCR heavy chain first appears on the cell surface in combination with the surrogate light chain, made up of VpreB and ʎ5, forming the pre-BCR. Signals through the pre-BCR activate several rounds of cell division.
Laser scanning confocal microscopy
Microscopy that uses lasers to focus on a single plane within the sample.
Lck
A tyrosine kinase that operates early in the TCR signaling cascade. Associates non-covalently with the T cell co-receptor.
Leader (L) peptide
A short hydrophobic sequence of amino acids at the N-terminus of newly synthesized immunoglobulins; it inserts into the lipid bilayer of the vesicles that transport Ig to the cell surface. The leader is removed from the ends of mature antibody molecules by proteolysis.
Lectin pathway
Pathway of complement activation initiated by binding of serum protein MBL to the mannose-containing component of microbial cell walls.
Lectins
Proteins that bind carbohydrates.
Leishmaniasis
The disease caused by the protozoan parasite Leishmania major.
Lepromatous leprosy
A disease caused by the intracellular bacteria Mycobacterium leprae and Mycobacterium lepromatosis, where skin, nerves, and upper respiratory tract are severely and chronically damaged by infection that is not successfully regulated by the immune response. This form of disease is associated with the production of a TH2 rather than TH1 response.
Leucine-rich repeats (LRRs)
Protein structural domains that contain many repeats of the leucine-containing 25-amino acid repeat sequence xLxxLxLxx.; the repeats stack up on each other. Found in TLR pattern-recognition receptors and in VLRs of jawless fish.
Leukemia
Cancer originating in any class of hematopoietic cell that tends to proliferate as single cells within the lymph or blood.
Leukocyte
A white blood cell. The category includes lymphocytes, granulocytes, platelets, monocytes, and macrophages.
Leukocyte adhesion deficiency (LAD)
An inherited immune deficiency disease in which the leukocytes are unable to undergo adhesion-dependent migration into sites of inflammation. Recurrent bacterial infections and impaired healing of wounds are characteristic of this disease.
Leukocytosis
An abnormally large number of leukocytes, usually associated with acute infection. Counts greater than 10,000/mm3 may be considered leukocytosis.
Leukotrienes
Several lipid mediators of inflammation and type I hypersensitivity, also called slow reactive substance of anaphylaxis (SRS-A). They are metabolic products of arachidonic acid.
Licensed APC
An antigen-presenting cell, usually a dendritic cell, that has been activated by interactions with helper T cells or signals from pattern-recognition receptors; it expresses costimulatory receptors (e.g., CD80/86) and can carry out cross-presentation.
Ligand
A molecule that binds to a receptor.
Light (L) chains
Immunoglobulin polypeptides of the lambda or kappa type that join with heavy-chain polypeptides to form the antibody heterodimer.
Light zone
A region of the germinal center that contains numerous follicular dendritic cells.
Lineage commitment
The development of a cell that can give rise to multiple cell types (multipotent) into one of those cell types. (1) In T cell development, the choice a CD4+CD8+ thymocyte makes to become a helper CD4+ versus cytotoxic CD8+ T cell. (2) In hematopoiesis, the choice a pluripotent stem cell makes to become either myeloid or lymphoid, as well as the subsequent choices to become specific immune cell subtypes.
Lipid rafts
Parts of the membrane characterized by highly ordered, detergent-insoluble, sphingolipid- and cholesterol-rich regions.
Lipopolysaccharide (LPS)
An oligomer of lipid and carbohydrate that constitutes the endotoxin of gram-negative bacteria. LPS acts as a polyclonal activator of murine B cells, inducing their division and differentiation into antibody-producing plasma cells.
Locus
The specific chromosomal location of a gene.
Lower respiratory tract
That part of the respiratory system that includes the smaller branches of the bronchi and the alveoli.
LPS tolerance
State of reduced responsiveness to LPS following an initial exposure to low/sublethal dose of LPS.
LRRs
See leucine-rich repeats.
Lumen
The inside of a tube or sac, such as the inside of the gastrointestinal system.
Ly49
Receptors in the C-lectin protein family expressed by murine natural killer cells that bind MHC class I and typically inhibit cytotoxicity.
Lymph
Interstitial fluid derived from blood plasma that contains a variety of small and large molecules, lymphocytes, and some other cells. It circulates through the lymphatic vessels.
Lymph node
A small secondary lymphoid organ that contains lymphocytes, macrophages, and dendritic cells and serves as a site for filtration of foreign antigen and for activation and proliferation of lymphocytes. See also germinal center.
Lymphatic system
A network of vessels and nodes that conveys lymph. It returns plasma-derived interstitial fluids to the bloodstream and plays an important role in the integration of the immune system.
Lymphatic vessels
Thinly walled vessels through which the fluid and cells of the lymphatic system move through the lymph nodes and ultimately into the thoracic duct, where it joins the bloodstream.
Lymphoblast
A proliferating lymphocyte.
Lymphocyte
A mononuclear leukocyte that mediates humoral or cell-mediated immunity. See also B cell and T cell.
Lymphoid progenitor cell
A cell committed to the lymphoid lineage from which all lymphocytes arise. Also known as common lymphoid progenitor (CLP).
Lymphoid-primed, multipotent progenitors (LMPPs)
Progenitor hematopoietic cells with the capacity to differentiate along either the lymphoid or the myeloid pathways.
Lymphoma
A cancer of lymphoid cells that tends to proliferate as a solid tumor.
Lymphotoxin-α (LT-α)
Also known as TNF-b, this cytokine is a member of the Tumor Necrosis Family. It is produced by activated lymphocytes and delivers a variety of signals to its target cells, including the induction of increased levels of MHC class II expression.
Lyn
A tyrosine kinase important in lymphocyte signaling.
Lysosome
A small cytoplasmic vesicle found in many types of cells that contains hydrolytic enzymes, which play an important role in the degradation of material ingested by phagocytosis and endocytosis.
Lysozyme
An enzyme present in tears, saliva, and mucous secretions that digests mucopeptides in bacterial cell walls and thus functions as a nonspecific antibacterial agent. Lysozyme from hen egg white (HEL) has frequently been used as an experimental antigen in immunological studies.
M cells
Specialized cells of the intestinal mucosa and other sites, such as the urogenital tract, that deliver antigen from the apical face of the cell to lymphocytes clustered in the pocket of its basolateral face.
Macrophages
Mononuclear phagocytic leukocytes that play roles in adaptive and innate immunity. There are many types of macrophages; some are migratory, whereas others are fixed in tissues.
Major histocompatibility complex (MHC)
proteins Proteins encoded by the major histocompatibility complex and classified as class I, class II, and MHC class III molecules. See also MHC.
Malignancy, malignant
Refers to cancerous cells capable of uncontrolled growth.
Mannose-binding lectin (MBL)
A serum protein that binds to mannose in microbial cell walls and initiates the lectin pathway of complement activation.
Mantle zone
See Follicular mantle zone.
MAP kinase cascade
Mitogen activated protein kinase cascade. A series of reactions initiated by a cellular signal that results in successive phosphorylations of intra-cellular kinases and culminates in activation of transcription factors within the nucleus and often the initiation of cellular locomotion.
Marginal zone
A diffuse region of the spleen, situated on the periphery of the periarteriolar lymphoid sheath (PALS) between the red pulp and white pulp, that is rich in B cells.
Marginal zone (MZ) B cells
Noncirculating B cells expressing high IgM and low IgD found in the splenic marginal zone; they have somewhat restricted receptor diversity. They generate T-independent antibody responses similar to B-1 B cells, and respond readily to blood-borne antigens entering the spleen.
Mast cell
A bone-marrow-derived cell present in a variety of tissues that resembles peripheral blood basophils, bears Fc receptors for IgE, and undergoes IgE-mediated degranulation.
Master gene regulator
A gene at the top of a hierarchy that regulates cell development; in immunology it often refers to the genes that initiate programs responsible for the differentiation of CD4+ T cells to distinct helper T-cell subsets; their induction is dependent on the activity of specific polarizing cytokines.
Mcl-1
Myeloid leukemia cell differentiation protein-1; anti-apoptotic protein that contributes to cell survival.
Medulla
The innermost or central region of an organ.
Medullary thymic epithelial cells (mTECs)
Stromal cells of epithelial origin that populate the medulla of the thymus and mediate clonal deletion of autoreactive thymocytes, particularly those expressing TCRs that recognize tissue-specific antigens.
Megakaryocytes
Hematopoietic cells in the myeloid system that give rise to platelets.
Membrane-attack complex (MAC)
The complex of complement components C5–C9, which is formed in the terminal steps of the classical, lectin, and alternative complement pathways and mediates cell lysis by creating a membrane pore in the target cell.
Membrane-bound immunoglobulin (mIg)
A form of antibody that is bound to a cell as a transmembrane protein. It acts as the antigen-specific receptor of B cells.
Memory B cell
An antigen-committed, persistent B cell. B-cell differentiation results in formation of plasma cells, which secrete antibody, and memory cells, which are involved in the secondary responses.
Memory cells
Lymphocytes generated following encounters with antigen that are characteristically long lived; they are more readily stimulated than naïve lymphocytes and mediate a secondary response to subsequent encounters with the antigen.
Memory response
See memory, immunologic.
Memory T cells
T cells generated during a primary immune response that become long lived and more easily stimulated by the antigen to which they are specific. They include two main subsets, central and effector memory T cells, and are among the first participants in the faster more robust secondary immune response to antigen.
Memory, immunologic
The attribute of the immune system mediated by memory cells whereby a second encounter with an antigen induces a heightened state of immune reactivity.
Mesenteric lymph nodes
The set of lymph nodes that drain the intestine; they can number from 100 to 200 and are situated in the membrane that connects the intestine to the wall of the abdomen (the mesentery).
Metastasis
The movement and colonization by tumor cells to sites distant from the primary site.
MHC (major histocompatibility complex) or MHC locus
A group of genes encoding cell-surface molecules that are required for antigen presentation to T cells and for rapid graft rejection. It is called the H-2 complex in the mouse and the HLA complex in humans.
MHC class I genes
The set of genes that encode MHC class I molecules, which are glycoproteins found on nearly all nucleated cells.
MHC class I molecules
Heterodimeric membrane proteins that consist of an a chain encoded in the MHC, associated noncovalently with β2-microglobulin. They are expressed by nearly all nucleated cells and function to present antigen to CD8+ T cells. The classical class I molecules are H-2 K, D, and L in mice and HLA-A, -B, and -C in humans.
MHC class II genes
The set of genes that encode MHC class II molecules, which are glycoproteins expressed by only professional antigen presenting cells.
MHC class II molecules
Heterodimeric membrane proteins that consist of a noncovalently associated a and b chain, both encoded in the MHC. They are expressed by antigen-presenting cells and function to present antigen to CD4+ T cells. The classical class II molecules are H-2 IA and IE in mice and HLA-DP, -DQ, and -DR in humans.
MHC class III genes
The set of genes that encode several different proteins, some with immune function, including components of the complement system and several inflammatory molecules.
MHC class III molecules
Various proteins encoded in the MHC but distinct from MHC class I and class II molecules. Among others, they include some complement components and TNF-α and Lymphotoxin-α.
MHC restriction
The characteristic of T cells that permits them to recognize antigen only after it is processed and the resulting antigenic peptide is displayed in association with either a MHC class I or a MHC class II molecule.
MHC tetramers
A soluble cluster of four MHC-peptide complexes used as a research tool to identify and trace antigen specific T cells in vitro and in vivo.
Microfold (M) cells
Specialized epithelial cells that cover Peyer’s patches and sample antigen from the intestinal lumen, delivering it to associated antigen-presenting cells in the intestinal mucosa. They are morphologically distinct, with a smooth apical surface and a pocket on the basolateral surface that allows intimate association with immune cells in the mucosa.
Microglial cell
A type of macrophage found in the central nervous system.
Microvilli
Folds in the membrane of epithelial cells that line mucosal tissues.
Minor histocompatibility loci
Genes outside of the MHC that encode antigens contributing to graft rejection.
Minor lymphocyte-stimulating (Mls) determinants
Antigenic determinants encoded by endogenous retroviruses of the murine mammary tumor virus family that are displayed on the surface of certain cells.
Missing self model
A model proposing that NK cell cytotoxicity is inhibited as long as they engage MHC class I with their receptors. However, when tumor cells and some virally infected cells reduce MHC class I expression, in other words, when they are “missing self” they are no longer protected from NK cytotoxicity.
Mitogen Activated Protein Kinase (MAPK)
The first kinase in a MAP kinase cascade.
Mitogens
Any substance that nonspecifically induces DNA synthesis and cell division. Common lymphocyte mitogens are concanavalin A, phytohemagglutinin, lipopolysaccharide (LPS), pokeweed mitogen, and various superantigens.
Mixed-lymphocyte reaction (MLR)
In vitro T-cell proliferation in response to cells expressing allogeneic MHC molecules; can be used as an assay for MHC class II activity.
Molecular mimicry
One hypothesis used explain the induction of some autoimmune diseases, positing that some pathogens express antigenic determinants resembling host self components which can induce anti-self reactivity.
Monoclonal antibody
Homogeneous preparation of antibody molecules, produced by a single clone of B lineage cells, often a hybridoma, all of which have the same antigenic specificity.
Monoclonal
Deriving from a single clone of dividing cells.
Monocytes
A mononuclear phagocytic leukocyte that circulates briefly in the bloodstream before migrating into the tissues where it becomes a macrophage.
Mucin
A group of serine- and threonine-rich proteins that are heavily glycosylated. They are ligands for selectins.
Mucociliary boundary
A protective layer of mucus produced by goblet cells in the epithelial lining of the respiratory tract; it traps foreign material, which is swept toward the mouth by ciliated epithelial cells.
Mucosa
The layer of the intestinal wall that includes the epithelial boundary and the lamina propria; where most immune cells in the gastrointestinal tract are found.
Mucosal-associated lymphoid tissue (MALT)
Lymphoid tissue situated along the mucous membranes that line the digestive, respiratory, and urogenital tracts.
Mucosal tissues
The subset of barrier organs whose epithelial tissues are covered with a mucus layer that provides additional protection as well as moisture; includes all barrier organs except the skin. All mucosal tissues have a mucosal layer and a submucosal layer. The mucosal layer includes the epithelial cells and the lamina propria.
Multiple myeloma
A plasma-cell cancer.
Multiple sclerosis (MS)
An autoimmune disease caused by auto-reactive T cells specific for components of the myelin sheaths which surround and insulate nerve fibers in the central nervous system. In Western countries, it is the most common cause of neurologic disability caused by disease.
Multipotential
Can divide to form daughter cells that are more differentiated than the parent cell and that can develop along distinct blood-cell lineages.
Multipotent progenitors (MPPs)
The stage of lymphoid differentiate that immediately precedes the LMPP stage. MPPs have lost the capacity for self-renewal that characterizes the true stem cell, but they retain the capacity to differentiate along many different hematopoietic lineages, including lymphoid, myeloid, erythroid, and megakaryocytic.
Multivalent
Having more than one ligand binding site.
Mutational hot spots
DNA sequences that are particularly susceptible to somatic hypermutation. Found in the variable regions of the immunoglobulin heavy and light chains.
Myasthenia gravis
An autoimmune disease mediated by antibodies that block the acetylcholine receptors on the motor end plates of muscles, resulting in progressive weakening of the skeletal muscles.
Mycoses
Any disease caused by fungal infection.
MyD88
Myeloid differentiation factor 88; adaptor protein that binds to all the IL-1 receptors and all TLRs except TLR3 and activates downstream signaling.
Myeloid progenitor cell
A cell that gives rise to cells of the myeloid lineage. Also known as a common myeloid progenitor (CMP).
Myeloma
A malignant tumor arising from cells of the bone marrow, specifically B cells.
Myeloma cell
A cancerous plasma cell.
N-nucleotides, N-region nucleotides
See Non-templated (N) nucleotides.
NADPH oxidase enzyme complex
Phagosome oxidase, activated by pathogen binding to pattern-recognition receptors on phagocytic cells, that generates reactive oxygen species from oxygen.
Naïve
Denoting mature B and T cells that have not encountered antigen; synonymous with unprimed and virgin.
Naïve BCR repertoire
The set of B-cell receptors that exists in an individual organism prior to its interaction with antigen.
Nasal-associated lymphoid tissue (NALT)
Secondary lymphoid microenvironments in the nose that support the development of the T and B lymphocyte response to antigens that enter nasal passages. Part of the mucosa associated lymphoid tissue system (MALT).
Natural antibodies
Antibodies spontaneously produced by B-1 and marginal zone B cells.
Natural killer (NK) cells
A class of large, granular, cytotoxic lymphocytes that do not have T- or B-cell receptors. They are antibody-independent killers of tumor cells and also can participate in antibody-dependent cell-mediated cytotoxicity.
Necrosis
Morphologic changes that accompany death of individual cells or groups of cells and that release large amounts of intracellular components to the environment, leading to disruption and atrophy of tissue. See also apoptosis.
Negative selection
The induction of death in lymphocytes bearing receptors that react too strongly with self antigens.
Neoadjuvant cancer therapies
Often compared to adjuvant cancer therapy, this treatment strategy involves administration of drugs or small molecule inhibitors prior to surgical removal of the tumor, with the goal of targeting metastatic cells and assessing drug efficacy by monitoring changes to the primary tumor evident at surgery.
Neoantigens
Unique epitopes that arise from mutations to DNA that are associated with cancer and that generate new, non-self proteins, which may be capable of eliciting an immune response.
Neonatal Fc receptor (FcRn)
An MHC class I–like molecule that controls IgG and albumin half-life and transports IgG across the placenta.
Neoplasm
Any new and abnormal growth; a benign or malignant tumor.
NETosis
Neutrophil cell death following release of neutrophil extracellular traps (NETs).
Neuraminidase (NA)
An enzyme that cleaves N-acetylneuraminic acid (sialic acid) from glycoproteins. Most commonly a virally-expressed enzyme found on the surface of influenza virus that facilitates viral attachment to and budding from host cells.
Neutralize
The ability of an antibody to prevent pathogens from infecting cells.
Neutralizing antibodies
Antibodies that bind to pathogen and prevent it from infecting cells. Our most powerful vaccines induce neutralizing antibodies.
Neutrophil
A circulating, phagocytic granulocyte involved early in the inflammatory response. It expresses Fc receptors and can participate in antibody-dependent cell-mediated cytotoxicity. Neutrophils are the most numerous white blood cells in the circulation.
Neutrophil extracellular traps (NETs)
Filaments of chromatin and proteins released by activated neutrophils that entrap and kill pathogens.
NF-κB
An important transcription factor, most often associated with pro-inflammatory responses.
NK cell licensing
The activation of an NK cell’s competence to kill appropriate target cells; it occurs following binding of the NK cell’s inhibitory receptors to MHC class I proteins, ensuring that functional NK cells have inhibitory receptors that recognize self MHC.
NKG2D
An activating receptor on NK cells that sends signals that enhance NK cytotoxic activity.
NK receptors (NKRs)
Activating and inhibitory receptors expressed by NK cells.
NKT cell
A subset of cytotoxic T cells that have features of both lymphocytes and innate immune cells. Like NK cells, they express NK1.1 and CD16, and like T cells they express TCRs, but these bind to glycolipids associated with an MHC class-I like molecule called CD1. iNKT cells are a subset of NKT cells that express very limited TCRab diversity.
Nod-like receptors (NLR)
Family of cytosolic pattern-recognition receptors with nuclear-binding/oligomerization and leucine-rich repeat domains; they have a nuclear-binding domain.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
An antiretroviral drug inhibits the viral reverse transcriptase enzyme in a non-competitive fashion, by binding outside the substrate binding site and inducing a conformation change that inhibits DNA polymerization.
Non-templated (N) nucleotides
Nucleotides added to the V-D and D-J junctions of immunoglobulin and TCR genes by the enzyme TdT.
Nonamer
A sequence of nine nucleotides that is partially conserved and serves, with the absolutely conserved heptamer, as a binding site for the RAG1/2 recombination enzymes. The heptamer:nonamer sequences are found down- and up-stream of each of the V, D, and J segments encoding the immunoglobulin and T cell receptors.
Nonclassical MHC molecules
A set of mostly nonpolymorphic proteins with some structural similarity to classical MHC molecules but with more restricted tissue expression and more limited roles in the immune response, some associated with the innate response. Examples of nonclassical Class I molecules include HLA-E, -F, and -G (human) or H2-Q, -M and -T (mouse). Class II examples include HLA-DM & -DO (human) or H2-M and -O (mouse).
Nonproductive rearrangement
Rearrangement in which gene segments are joined out of phase so that the triplet-reading frame for translation is not preserved.
Northern blotting
Common technique for detecting specific mRNAs, in which denatured mRNAs are separated electrophoretically and then transferred to a polymer sheet, which is incubated with a radiolabeled DNA probe specific for the mRNA of interest.
NOS2
see Inducible nitric oxide synthetase.
Notch
A surface receptor that when bound is cleaved to release a transcriptional regulator that regulates cell fate decisions. Notch activation is required for T cell development and determines whether a lymphocyte precursor becomes a B versus T cell.
nTREG cells
A type of T cell that is induced to express FoxP3 and acquire regulatory function during development in the thymus, and is responsible for suppressing immune activity against specific antigen. See also iTREG cells.
Nuclear Factor of Activated T cells (NFAT)
A transcription factor activated by TCR ligation. NFAT is held in the cytoplasm by the presence of a bound phosphate group. Activation through the TCR results in the activation of a phosphatase that releases the bound phosphate and facilitates entry of NFAT into the nucleus.
Nucleoside reverse transcriptase inhibitors (NRTIs)
An antiretroviral drug composed of nucleoside analogues which compete with native cellular nucleosides for binding to the viral reverse transcriptase enzyme but which lead to DNA chain termination and therefore halt viral DNA synthesis.
Nucleotide oligomerization domain/leucine-rich repeat-containing receptors (NLR)
see Nod-like receptors (NLR).
Nude mouse
Homozygous genetic defect (nu/nu) carried by an inbred mouse strain that results in the absence of the thymus and consequently a marked deficiency of T cells and cell-mediated immunity. The mice are hairless (hence the name) and can accept grafts from other species.
Oncofetal tumor antigen
An antigen that is present during fetal development but generally is not expressed in tissues except following transformation. Alpha-feto protein (AFP) and carcinoembryonic antigen (CEA) are two examples that have been associated with various cancers.
Oncogene
A gene that encodes a protein capable of inducing cellular transformation. Oncogenes derived from viruses are written v-onc; their counterparts (proto-oncogenes) in normal cells are written c-onc.
One-turn recombination signal sequences
Immunoglobulin gene-recombination signal sequences separated by an intervening sequence of 12 base pairs.
Opportunistic infections
Infections caused by ubiquitous microorganisms that cause no harm to immune competent individuals but that pose a problem in cases of immunodeficiency.
Opsonin
A substance (e.g., an antibody or C3b) that promotes the phagocytosis of antigens by binding to them.
Opsonization, opsonize
Deposition of opsonins on an antigen, thereby promoting a stable adhesive contact with an appropriate phagocytic cell.
Original antigenic sin
The concept that a secondary response relies on the activity of memory cells rather than the activation of naïve cells, focusing on those structures that were present during the original, or primary, encounter with a pathogen and ignoring any new antigenic determinants.
Osteoclast
A bone macrophage.
Oxidative burst
Metabolic reactions that use large amounts of oxygen to generate toxic oxygen metabolites such as hydrogen peroxide, oxygen free radicals, hypochlorous acid, and various oxides of nitrogen. These metabolites are generated within specialized vesicles in neutrophils and macrophages and are used to kill invading pathogens.
P-addition
See P-nucleotide addition.
P-K reaction
Prausnitz-Kustner reaction, a local skin reaction to an allergen by a normal subject at the site of injected IgE from an allergic individual. (No longer used because of risk of transmitting hepatitis or AIDS.)
P-nucleotide addition
Addition of nucleotides from cleaved hairpin loops formed by the junction of V-D or D-J gene segments during Ig or TCR gene rearrangements.
P-region nucleotides
See Palindromic (P) nucleotides.
Palindromic (P) nucleotides
Nucleotides formed at the V-D and D-J junctions by asymmetric clipping of the hairpin junction formed by RAG1/2-mediated DNA cleavage.
PALS
See Periarteriolar lymphoid sheath.
Paneth cells
Specialized cells in the epithelium of the small intestine that secrete molecules that regulate the interaction with microbes, including antimicrobial peptides (AMPs) such as defensins; Paneth cells also help maintain stem cells in the intestinal crypt.
Papain
A proteolytic enzyme derived from papayas and pineapples. Papain cleavage of immunoglobulins releases two Fab and one Fc fragment per IgG.
Paracortex
An area of the lymph node beneath the cortex that is populated mostly by T cells and interdigitating dendritic cells.
Paracrine
A type of regulatory secretion, such as a cytokine, that arrives by diffusion from a nearby cellular source.
Passive immunity
Temporary adaptive immunity conferred by the transfer of immune products, such as antibody (antiserum), from an immune individual to a nonimmune one. See also active immunity.
Passive immunotherapy
Treatment of an infectious disease by administration of previously generated antibodies specific for the infectious pathogen.
Pathobionts
Members of the commensal microbiome in healthy animals that are typical harmless, but have the potential to cause disease under certain conditions (e.g., if the immune system is perturbed).
Pathogen
A disease-causing infectious agent.
Pathogen-associated molecular patterns (PAMPs)
Molecular patterns common to pathogens but not occurring in mammals. PAMPs are recognized by various pattern-recognition receptors of the innate immune system.
Pathogenesis
The means by which disease-causing organisms attack a host.
Pattern recognition receptors (PRRs)
Receptors of the innate immune system that recognize molecular patterns or motifs present on pathogens but absent in the host.
Pattern recognition
The ability of a receptor or ligand to interact with a class of similar molecules, such as mannose-containing oligosaccharides.
PAX5 transcription factor
A quintessential B cell transcription factor that controls the expression of many B cell specific genes.
Pentraxins
A family of serum proteins consisting of five identical globular subunits; CRP is a pentraxin.
Perivascular niche
Microenvironment in the bone marrow, adjacent to the blood vessels, that fosters the development of hematopoietic stem cells.
Perforin
Cytolytic product of CTLs that, in the presence of Ca2+, polymerizes to form transmembrane pores in target cells.
Periarteriolar lymphoid sheath (PALS)
A collar of lymphocytes encasing small arterioles of the spleen.
Peripheral TREG (pTREG) cells
A class of T cell that, following antigen exposure in the periphery, is induced to express FoxP3 and acquire regulatory functions, suppressing immune activity against specific antigen. See also Thymic TREG (tTREG) cells.
Peripheral tolerance
Process by which self-reactive lymphocytes in the circulation are eliminated, rendered anergic, or otherwise inhibited from inducing an immune response.
Peyer’s patches
Lymphoid follicles situated along the wall of the small intestine that trap antigens from the gastrointestinal tract and provide sites where B and T cells can interact with antigen.
PH domain
See Pleckstrin homology (PH) domain.
Phage display library
Collection of bacteriophages engineered to express specific VH and VL domains on their surface.
Phagocytes
Cells with the capacity to internalize and degrade microbes or particulate antigens; neutrophils and monocytes are the main phagocytes.
Phagocytosis
The cellular uptake of particulate materials by engulfment; a form of endocytosis.
Phagolysosome
An intracellular body formed by the fusion of a phagosome with a lysosome.
Phagosome
Intracellular vacuole containing ingested particulate materials; formed by the fusion of pseudopodia around a particle undergoing phagocytosis.
Phagosome oxidase (phox)
See NADPH oxidase enzyme complex.
Phosphatidyl Inositol bis-Phosphate (PIP2)
A phospholipid found on the inner leaflet of cell membranes that is cleaved on cell signaling into the sugar inositol trisphosphate and diacylglycerol.
Phosphatidyl Inositol tris-Phosphate (PIP3)
The product of PIP2 phosphorylation. PIP3 is bound by signaling proteins bearing PH domains.
Phosphatidyl Inositol-3-kinase (PI3 kinase)
A family of enzymes that phosphorylate the inositol ring of phosphatidyl inositols at the 3 position. On immune signaling, the usual substrate is PIP2.
Phosphatidyl serine
Membrane phospholipid. Normally located on the inner membrane leaflet, but flips to the outside leaflet in apoptotic cells.
Phospholipases C
ϓ (PLCϓ) A family of enzymes that cleave phosphatidyl inositol bis-phosphate into the sugar inositol tris-phosphate and the lipid diacylglycerol.
Physical barriers
Tissue layers, especially epithelia, whose physical integrity blocks infection.
PKC
θ A serine/threonine protein kinase activated by diacylglycerol and important in TCR signaling.
Plasma cell
The antibody-secreting effector cell of the B lineage.
Plasma
The cell-free, fluid portion of blood, which contains all the clotting factors.
Plasmablasts
Cells that have begun the pathway of differentiation to plasma cells, but have not yet reached the stage of terminal differentiation and are therefore still capable of cell division.
Plasmacytomas
A plasma-cell cancer.
Plasmapheresis
A procedure that involves the separation of blood into two components, plasma and cells. The plasma is removed and cells are returned to the individual. This procedure is done during pregnancy when the mother makes anti-Rh antibodies that react with the blood cells of the fetus.
Plasmin
A serine protease formed by cleavage of plasminogen. Its major function is the hydrolysis of fibrin.
Platelets
Cells in the myeloid system that arise from megakaryocytes and regulate blood clotting.
Pleckstrin homology (PH) domain
A protein domain that binds specifically to phosphatidyl inositol tris-phosphate or phosphatidyl inositol bis-phosphate. These domain interactions are important in a wide variety of signaling cascades, including those initiated by ligand binding at the TCR and BCR.
Pleiotropic
Having more than one effect. For example, a cytokine that induces both proliferation and differentiation.
Poly-Ig receptor
A receptor for polymeric Ig molecules (IgA or IgM) that is expressed on the basolateral surface of most mucosal epithelial cells. It transports polymeric Ig across epithelia.
Polarizing cytokines
Cytokines that regulate which helper subset naïve CD4+ T cells will differentiate into; they are produced by immune cells as well as a variety of other cell types.
Polyclonal antibody
A mixture of antibodies produced by a variety of B-cell clones that have recognized the same antigen. Although all of the antibodies react with the immunizing antigen, they differ from each other in amino acid sequence.
Polygenic
The presence of multiple genes within the genome that encode proteins with the same function but slightly different structures.
Polymorphic, polymorphism
The presence of multiple allelic forms of a gene (alleles) within a population, as occurs within the major histocompatibility complex.
Positional cloning
A technique to identify a gene of interest that involves using known genetic markers to identifying a specific region in the genome associated with a characteristic of interest (e.g. disease susceptibility). This region is then cloned and sequenced to discover specific gene or genes that may be directly involved.
Positive selection
A process that permits the survival of only those T cells whose T-cell receptors recognize self MHC.
Potential candidate genes
List of genes that could be involved in the condition of interest, identified as a result research and educated guesses.
Pre-B-cell (first) checkpoint
Developing B cells are tested at the pre-B cell stage to determine whether they can express a functional BCR heavy chain protein, in combination with the VPreB and ʎ5 proteins, to form the pre-B-cell receptor. Those B cells that fail to form a functional pre-B-cell receptor are eliminated by apoptosis and are referred to as having failed to pass through the pre-B-cell checkpoint.
Pre-B-cell receptor
A complex of the Iga,Igb heterodimer with membrane-bound Ig consisting of the m heavy chain bound to the surrogate light chain Vpre-B/l5.
Pre-pro-B cell
Earliest stage in B-lineage development; initial expression of the B-cell marker B220.
Pre-T-cell receptor (pre-TCR)
A complex of the CD3 group with a structure consisting of the T-cell receptor b chain complexed with a 33-kDa glycoprotein called the pre-Ta chain.
Pre–B cell (precursor B cell)
The stage of B-cell development that follows the pro-B-cell stage. Pre-B cells produce cytoplasmic m heavy chains and most display the pre-B-cell receptor.
pre–Tα chain
An invariant protein homolog of the TCRa chain that is expressed in early T cell development and pairs with newly rearranged TCRb to form the pre-T cell receptor. This receptor delivers a signal that induces proliferation and differentiation to the CD4+CD8+ stage, when the TCRa chain is rearranged and if successfully translated into a protein takes the place of the pre-Ta.
Precipitin
An antibody that aggregates a soluble antigen, forming a macromolecular complex that yields a visible precipitate.
Primary foci
Clusters of antigen-stimulated dividing B cells found at the borders of the T and B cell areas of the lymph nodes and spleen that secrete IgM quickly after antigen stimulation.
Primary follicle
A lymphoid follicle, prior to stimulation with antigen, that contains a network of follicular dendritic cells and small resting B cells.
Primary immunodeficiency
An inherited genetic or developmental defect in some component/s of the immune system.
Primary lymphoid organs
Organs in which lymphocyte precursors mature into antigenically committed, immunocompetent cells. In mammals, the bone marrow and thymus are the primary lymphoid organs in which B-cell and T-cell maturation occur, respectively.
Primary response
Immune response following initial exposure to antigen; this response is characterized by short duration and low magnitude compared to the response following subsequent exposures to the same antigen (secondary response).
Pro–B cell (progenitor B cell)
The earliest distinct cell of the B-cell lineage.
Productive rearrangement
The joining of V(D)J gene segments in phase to produce a VJ or V(D)J unit that can be translated in its entirety.
Professional antigen-presenting cell (pAPC)
A myeloid cell with the capacity to activate T lymphocytes. Dendritic cells, macrophages, and B cells are all considered professional APCs because they can present antigenic peptide in both MHC class I and class II and express costimulatory ligands necessary for T cell stimulation.
Progenitor cell
A cell that has lost the capacity for self renewal and is committed to the generation of a particular cell lineage.
Programmed death-1 (PD-1 or CD279)
A coinhibitory receptor that blocks T-cell activation, acting as a checkpoint that down-regulates immune responses; up-regulated by T cells after activation.
Proinflammatory
Tending to cause inflammation; TNF-α, IL-6 and IL-1 are examples of proinflammatory cytokines.
Properdin
Component of the alternative pathway of complement activation that stabilizes the alternative pathway C3 convertase C3bBb.
Prostaglandins
A group of biologically active lipid derivatives of arachidonic acid. They mediate the inflammatory response and type I hypersensitivity reaction by inhibiting platelet aggregation, increasing vascular permeability, and inducing smooth-muscle contraction.
Protease inhibitors
The common name for a class of antiviral medications that inhibit virus-specific proteases and therefore interfere with viral replication. Most often associated with anti-HIV drug therapy.
Proteasome
A large multifunctional protease complex responsible for degradation of intracellular proteins.
Protectin
See CD59.
Protein A
An FC-binding protein present on the membrane of Staphylococcus aureus bacteria. It is used in immunology for the detection of antigen-antibody reactions and for the purification of antibodies.
Protein A/G
A genetically engineered FC-binding protein that is a hybrid of protein A and protein G. It is used in immunology for the detection of antigen-antibody reactions and for the purification of antibodies.
Protein G
An FC-binding protein present on the membrane of Streptococcus bacteria. It is used in immunology for the detection of antigen-antibody reactions and for the purification of antibodies.
Protein kinase C (PKC)
A family of serine/threonine protein kinases activated by diacylglycerol.
Protein scaffold
A set of proteins that binds together in a defined way to bring together molecules that would otherwise not come into contact. Protein scaffolds usually include a number of adapter proteins that then serve to bring enzyme and substrate proteins into apposition with the resultant activation or inhibition of the substrate protein.
Proto-oncogene
A cancer-associated gene that encodes a factor that normally regulates cell proliferation, survival, or death; these genes are required for normal cellular functions. When mutated or produced in inappropriate amounts, a proto-oncogene becomes an oncogene, which can cause transformation of the cell.
Provirus
Viral DNA that is integrated into a host-cell genome in a latent state and must undergo activation before it is transcribed, leading to the formation of viral particles.
Pseudogene
Nucleotide sequence that is a stable component of the genome but is incapable of being expressed. Pseudogenes are thought to have been derived by mutation of ancestral active genes.
Pseudopodia
Membrane protrusions that extend from motile and phagocytosing cells.
Psoriasin
A protein produced by keratinocytes that has potent antimicrobial properties, particularly against Escherichia coli.
Purine box factor 1 (PU.1)
A transcription factor important in B cell development and survival.
Pyroptosis
A form of regulated programmed cell death associated with inflammation, and often associated with infection with intracellular pathogens. Mediated by inflammasome-activated caspase-1.
Radioimmunoassay (RIA)
A highly sensitive technique for measuring antigen or antibody that involves competitive binding of radiolabeled antigen or antibody.
RAG1/2 (recombination-activating genes 1 and 2)
The protein complex of RAG1 and RAG2 that catalyzes V(D)J recombination of B- and T-cell receptor genes. These proteins operate in association with a number of other enzymes to bring about the process of recombination, but RAG1/2, along with TdT, represent the lymphoid-specific components of the overall enzyme complex.
RAG1 (Recombination Activating Gene 1)
See RAG1/2.
RAG2 (Recombination Activating Gene 2)
See RAG1/2.
Ras
Small, monomeric G protein important in signaling cascades.
Reactive nitrogen species
Highly cytotoxic antimicrobial compounds formed by the combination of nitric oxide and superoxide anion within phagocytes such as neutrophils and macrophages.
Reactive oxygen species (ROS)
Highly reactive compounds such as superoxide anion ·2-, hydroxyl radicals (OH?)(OH2), hydrogen peroxide (H2O2), and hypochlorous acid (HClO) that are formed from oxygen under many conditions in cells and tissues, including microbe-activated innate responses of phagocytic cells; have anti-microbial activity.
Recent thymic emigrants (RTEs)
Newly developed single positive (CD4+ or CD8+) thymocytes that been allowed to leave the thymus. These new T cells still bear features of immature T cells and undergo further maturation in the periphery before joining the circulating fully mature, naïve T cell pool.
Receptor
A molecule that specifically binds a ligand.
Receptor editing
Process by which the T- or B-cell receptor sequence is altered after the initial recombination event, in order to reduce affinity for self antigens.
Recombinant inbred strains
Mouse strains created by the mating of two inbred strains, with the formation of a recombination in an interesting locus such as the MHC. The mice bearing the recombination are then inbred to create a new inbred strain.
Recombination signal sequences (RSSs)
Highly conserved heptamer and nonamer nucleotide sequences that serve as signals for the gene rearrangement process and flank each germ-line V, D, and J segment.
Recombination-activating genes
See RAG1/2.
Red pulp
Portion of the spleen consisting of a network of sinusoids populated by macrophages and erythrocytes. It is the site where old and defective red blood cells are destroyed.
Redundant
Having the same effect as another signal.
Regulated cell death
Activated or induced cell death, including apoptosis, necroptosis, pyroptosis, and NETosis.
Regulatory T cell (TREG)
A type of CD4+ T cell that that negatively regulates immune responses. It is defined by expression of the master regulator FoxP3 and comes in two versions, the induced TREG, which develops from mature T cells in the periphery, and the natural TREG, which develops from immature T cells in the thymus.
Relative risk
Probability that an individual with a given trait (usually, but not exclusively, a genetic trait) will acquire a disease compared with those in the same population group who lack that trait.
Resident memory T cells (TRM)
A class of memory T cell that homes to and spends long periods of time in mucosal tissues and skin, where they participate with innate cells in the first line of defense against reinfection.
Resonant angle
A property measured when using surface plasmon resonance to assess the affinity of the interaction between two molecules.
Respiratory burst
A metabolic process in activated phagocytes in which the rapid uptake of oxygen is used to produce reactive oxygen species that are toxic to ingested microorganisms.
Reticular dysgenesis (RD)
A type of severe combined immunodeficiency (SCID) in which the initial stages of hematopoietic cell development are blocked by defects in the adenylate kinase 2 gene (AK2), favoring apoptosis of myeloid and lymphoid precursors and resulting in severe reductions in circulating leukocytes.
Retinoic acid-inducible gene-I-like receptors (RLRs)
A family of cytosolic pattern-recognition receptors named for one member, RIG-I; known members are RNA helicases with CARD domains.
Retrovirus
A type of RNA virus that uses a reverse transcriptase to produce a DNA copy of its RNA genome. HIV, which causes AIDS, and HTLV, which causes adult T-cell leukemia, are both retroviruses.
Reverse transcriptase (RT)
The polymerase of retroviruses, such as HIV, which copies the virus’s RNA genome into a complementary DNA copy.
Rh antigen
Any of a large number of antigens present on the surface of blood cells that constitute the Rh blood group. See also erythroblastosis fetalis.
Rheumatoid arthritis
A common autoimmune disorder, primarily diagnosed in women 40 to 60 years old, caused by self-reactive antibodies called rheumatoid factors, which mediate chronic inflammation of the joints.
Rheumatoid factors
Auto-antibodies found in the serum of individuals with rheumatoid arthritis and other connective-tissue diseases.
Rhogam
Antibody against Rh antigen that is used to prevent erythroblastosis fetalis.
Rous sarcoma virus (RSV)
A retrovirus that induces tumors in avian species.
Runx1
Transcription factor in hematopoiesis that contributes to the activation of the EBF1 transcription factor during B-cell development.
Sarcoma
Tumor of supporting or connective tissue.
Schistosomiasis
A disease caused by the parasitic worm Schistosoma.
SCID
See Severe combined immunodeficiency.
SCID-human mouse
Immunodeficient mouse into which elements of a human immune system, such as bone marrow and thymic fragments, have been grafted. Such mice support the differentiation of pluripotent human hematopoietic stem cells into mature immunocytes and so are valuable for studies on lymphocyte development. See also Severe combined immunodeficiency.
SDS-polyacrylamide gel electrophoresis (SDS-PAGE)
An electrophoretic method for the separation of proteins. It employs SDS to denature proteins and give them negative charges; when SDS-denatured proteins are electrophoresed through polymerized-acrylamide gels, they separate according to their molecular weights.
Secondary follicle
A primary follicle after antigenic stimulation; it develops into a ring of concentrically packed B cells surrounding a germinal center.
Secondary immune response
The immune response to an antigen that has been previously introduced and recognized by adaptive immune cells. It is mediated primarily by memory T and B lymphocytes that have differentiated to respond more quickly and robustly to antigenic stimulation than the primary response.
Secondary immunodeficiency
Loss of immune function that results from exposure to an external agent, often an infection.
Secondary lymphoid organs (SLOs)
Organs and tissues in which mature, immunocompetent lymphocytes encounter trapped antigens and are activated into effector cells. In mammals, the lymph nodes, spleen, and mucosal-associated lymphoid tissue (MALT) constitute the secondary lymphoid organs.
Secondary response
See Secondary immune response.
Secreted immunoglobulin (sIg)
The form of antibody that is secreted by cells of the B lineage, especially plasma cells. This form of Ig lacks a transmembrane domain. See also Membrane immunoglobulin (mIg).
Secretory component
A fragment of the poly-Ig receptor that remains bound to Ig after transcytosis across an epithelium and cleavage.
Secretory IgA
J chain–linked dimers or higher polymers of IgA that have transited epithelia and retain a bound remnant of the poly-Ig receptor.
Selectin
One of a group of monomeric cell adhesion molecules present on leukocytes (L-selectin) and endothelium (E- and P-selectin) that bind to mucin-like CAMs (e.g., GlyCAM, PSGL-1).
Self-MHC restriction
The property of recognizing antigenic peptides only in the context of self MHC molecules.
Self-renewing
Can divide to create identical copies of the parent cell.
Self-tolerance
Unresponsiveness to self antigens.
Sepsis
Infection of the bloodstream, frequently fatal.
Septic shock
Shock induced by septicemia.
Septicemia
Blood poisoning due to the presence of bacteria and/or their toxins in the blood.
Seroconversion
The stage of HIV infection at which anti-HIV antibodies first are detected in the serum.
Serum
Fluid portion of the blood, which is free of cells and clotting factors.
Serum sickness
A type III hypersensitivity reaction that develops when antigen is administered intravenously, resulting in the formation of large amounts of antigen-antibody complexes and their deposition in tissues. It often develops when individuals are immunized with antiserum derived from other species.
Severe combined immunodeficiency (SCID)
A genetic defect in which adaptive immune responses do not occur, due to a lack of T cells and possibly B and NK cells.
SH2 domain
A protein domain that binds phosphorylated tyrosine residues.
SH3 domain
A protein domain that binds proline-rich peptides.
SIGN-R1
A cell-surface receptor for the complement component C1q.
Signal
A molecule that elicits a respond in a cell bearing a receptor for that signal. The response may be cell movement, cell division, activation of cell metabolism, or even cell death.
Signal joints
In V(D)J gene rearrangement, the nucleotide sequences formed by the union of recombination signal sequences.
Signal peptide
A small sequence of amino acids, also called the leader sequence, that guides the heavy or light chain through the endoplasmic reticulum and is cleaved from the nascent chains before assembly of the finished immunoglobulin molecule.
Signal Transducer and Activator of Transcription (STAT)
Transcription factors that normal reside in the cytoplasm. Phosphorylation of cytokine receptors by Janus Activated Kinases results in the generation of binding sites on those receptors for the STATs, which relocate to the cytoplasmic regions of the receptor and are themselves phosphorylated by JAKs. Phosphorylated STATs them dimerize. Phosphorylation and dimerization expose nuclear localization signals and the STATs move to the nucleus where they act as transcription factors.
Signal transduction
The process by which a molecular signal is passed from one part of a cell to another, usually by the binding of a signaling molecule to a receptor at the cell surface, followed by a conformational change in the receptor that causes a cascade of intracellular events, culminating in an alteration in transcription of one or more genes.
Signal transduction pathway
A sequence of intra-cellular events brought about by receipt of a signal by a specific receptor.
Signaling
Intracellular communication initiated by receptor-ligand interaction.
Single nucleotide polymorphisms (SNPs)
A single base-pair variation in a DNA sequence among individuals in a population (i.e. an allelic variation). SNPs are often found in non-coding regions of the genome and can be used as genetic markers to locate genes that may underlie differences in individual responses to disease.
Single-positive (SP) stage
Either CD4+CD8− or CD8+CD4− mature T lymphocytes.
Skin-associated lymphoid tissue (SALT)
The immune cells and immune system associated specifically with the skin; includes Langerhans cells, a skin-specific antigen-presenting cell.
Slow-reacting substance of anaphylaxis (SRS-A)
The collective term applied to leukotrienes that mediate inflammation.
Small pre-B-cell
The stage in B-cell development, following the large pre-B-cell stage, where the pre-B-cell receptor is lost from the B-cell surface and light-chain recombination begins in the genome.
Somatic hypermutation (SHM)
The induced increase of mutation, 103- to 106-fold over the background rate, in the regions in and around rearranged immunoglobulin genes. In animals such as humans and mice, somatic hypermutation occurs in germinal centers.
S1P2-type receptor
A receptor for sphingosine 1-phosphate that acts as a chemokine in the lymph nodes.
Specificity, antigenic
Capacity of antibody and T-cell receptor to recognize and interact with a single, unique antigenic determinant or epitope.
Sphingosine 1-phosphate (S1P)
A sphingolipid that plays a role in immune cell trafficking. Interactions between S1P and its membrane receptors, including S1P1, are required for immune cell egress from lymphoid tissue, including lymph nodes and thymus.
Spleen
Secondary lymphoid organ where old erythrocytes are destroyed and blood-borne antigens are trapped and presented to lymphocytes in the PALS and marginal zone.
Splenectomy
Surgical removal of the spleen.
Splenic artery
The blood vessel that provides the spleen with nutrients and oxygen; it is the source of immune cells that populate the splenic environment.
Splenic vein
Vein that drains blood from the spleen and the site of egress of many splenic white blood cells.
Spliceosome
The complex of enzymes that mediates splicing of RNA.
Src-family kinases
A family of tyrosine kinase critically important in the early stages of signaling pathways in many cell types, including lymphocytes.
STAT5
See Signal Transducer and Activator of Transcription.
Stem cell
A cell from which differentiated cells derive. Stem cells are classified as totipotent, pluripotent, multipotent, or unipotent depending on the range of cell types that they can generate.
Stem cell associated antigen-1 (Sca-1)
An antigen present on hematopoietic stem cells.
Stem cell factor (SCF)
A cytokine that exists in both membrane-bound and soluble forms. The SCF/c-Kit interaction is critical for the development, in adult animals, of multipotential progenitor cells (MPPs).
Stem-cell memory T cells (TSCM)
A class of memory T cell that has self-renewing properties and, when stimulated, can give rise to all effector cell populations, as well as more stem cells.
Stem cell niches
Cellular microenvironments in the bone marrow (and some other tissues) that support the development of hematopoietic stem cells. Two are recognized: the endosteal niche, in proximity to bone cells (osteoblasts) and the vascular niche, in proximity to cells that line the blood vessels (endothelial cells).
Sterilizing immunity
A memory response or immune status that blocks the ability of a potential pathogen to infect an individual during exposure to the infectious agent in question.
STING
Stimulator of interferon genes. An endoplasmic reticulum-associated cytosolic protein that binds cyclic dinucleotides and activates downstream signaling leading to production of type I interferons and other innate immune mediators.
Stochastic model
A model advanced to explain the molecular basis for lineage commitment, the choice of a CD4+CD8+ thymocyte to become a CD4+ versus a CD8+ T cell. This model proposes that all DP thymocytes receiving T cell receptor signals randomly decrease expression of either co-receptor CD4 or CD8. Only those thymocytes expressing the co-receptor that stabilizes the TCR-MHC interaction they experience will mature successfully. For example, a DP thymocyte that expresses a TCR with an affinity for MHC class I but randomly down-regulates CD8 will not receive adequate stimulation and will not mature. However, if that thymocyte randomly down-regulates CD4, it will maintain a TCR signal and mature to the CD8 lineage.
Strength of signal model
A model for thymocyte lineage commitment proposing that strong TCR signals favor development to the CD4 lineage and weak TCR signals favor development to the CD8 lineage.
Streptavidin
A bacterial protein that binds to biotin with very high affinity. It is used in immunological assays to detect antibodies that have been labeled with biotin.
Stromal cell
A nonhematopoietic cell that supports the growth and differentiation of hematopoietic cells.
Sub-isotypes
A particular antibody subclass, e.g., IgG1 or IgA2.
Subcapsular sinus (SCS) macrophages
Macrophages that line the subcapsular sinus of the lymph nodes.
Subclasses
Variant sequences of the constant regions of antibodies of the IgG and IgA classes. There are four common variants of IgG and two of IgA in both mice and humans.
Submucosa
The layer of connective tissue in the intestinal wall just beneath the mucosa; the site of a network of blood vessels, lymphatics, and nerves.
Superantigens
Any substance that binds to the Vb domain of the T-cell receptor and residues in the chain of MHC class II molecules. It induces activation of all T cells that express T-cell receptors with a particular Vb domain. It functions as a potent T-cell mitogen and may cause food poisoning and other disorders.
Surface plasmon resonance (SPR)
An instrumental technique for measurement of the affinity of molecular interactions based on changes of reflectance properties of a sensor coated with an interactive molecule.
Surfactants
In innate immunity, collectins that associate with microbe surfaces and promote phagocytosis.
Surrogate light chain
The polypeptides Vpre-B and ʎ5 that associate with m heavy chains during the pre-B-cell stage of B-cell development to form the pre-B-cell receptor.
SWI/SNF
A chromatin-modifying complex; it remodels nucleosomes by destabilizing the interactions of histones with DNA, providing access to transcription factors and facilitating gene expression.
Switch (S) regions
In class switching, DNA sequences located upstream of each CH segment (except Cᵟ).
Synergy
The property of two separate signals having an effect that is greater than the sum of the two signals.
Syngeneic
Denoting genetically identical individuals.
Systemic lupus erythematosus (SLE)
A multi-system autoimmune disease characterized by auto-antibodies to a vast array of tissue antigens such as DNA, histones, RBCs, platelets, leukocytes, and clotting factors.
T cell
See T lymphocyte.
T cytotoxic (TC) cells
See cytotoxic T lymphocytes.
T helper (TH) cells
T cells that are stimulated by antigen to provide signals that promote immune responses.
T helper type 1 (TH1) cells
Helper CD4+ T cell subset that enhances the cytotoxic immune response against intracellular pathogens and expresses the master transcriptional regulator T-Bet.
T helper type 17 (TH17) cells
Helper CD4+ T cell subset that enhances an inflammatory immune response against some fungi and bacteria and expresses the master transcriptional regulator RORg.
T helper type 2 (TH2) cells
Helper CD4+ T cell subset that enhances B cell production of IgE and the immune response to pathogenic worms. It expresses the master transcriptional regulator GATA-3.
T lymphocyte
A lymphocyte that matures in the thymus and expresses a T-cell receptor, CD3, and CD4 or CD8.
T-cell hybridoma
An artificially generated T cell tumor formed by fusing a single T cell with a naturally-occurring thymoma cell.
T-cell receptor (TCR)
Antigen-binding molecule expressed on the surface of T cells and associated with the CD3 molecule. TCRs are heterodimeric, consisting of either an a and b chain or a g and d chain.
T-dependent (TD) response
An antibody response elicited by a T-dependent antigen.
T-helper type 9 (TH9) cells
A helper T-cell subset that generates the effector cytokine IL-9 and regulates the response to worms; they also contribute to allergy and asthma symptoms.
T-helper type 22 (TH22) cells
A helper T-cell subset that generates the effector cytokines IL-22 and TNF-α; they play a major role in skin immune responses and may regulate wound healing as well as contribute to chronic skin inflammatory conditions.
T-independent (TI) response
An antibody response elicited by a T-dependent antigen.
TAB1
TAK1-binding protein 1.
TAB2
TAK1-binding protein 2.
TACI receptor
Transmembrane activator and CAML interactor.
TAK1
See Transforming growth factor-beta-kinase-1.
TAP (transporter associated with antigen processing)
Heterodimeric protein present in the membrane of the rough endoplasmic reticulum (RER) that transports peptides into the lumen of the RER, where they bind to MHC class I molecules.
Target cell
Any self cell expressing MHC-peptide that is recognizable by a cytotoxic T cell (whether due to viral infection, cancer or defective), that becomes a target for recognition and lysis by Tc cells.
Tapasin
TAP-associated protein. Found in the ER that brings the TAP transporter into proximity with the MHC class I molecule, allowing it to associate with antigenic peptide.
TATA box
A Thymidine and Adenine-rich sequence upstream of many genes that serves as part of the RNA polymerase recognition and binding sequence.
TC1 cells
Cytotoxic T cells that produce IFN-γ and induce target cell apoptosis by perforin and FasL-mediated pathways.
TC2 cells
Cytotoxic T cells that produce IL-4 and IL-5, and induce target cell apoptosis by the perforin pathway.
TD antigen
See Thymus-dependent (TD) antigen.
Terminal deoxynucleotidyl transferase (TdT)
Enzyme that adds untemplated nucleotides at the V-D and D-J junctions of B and T cell receptor genes.
Tertiary lymphoid tissue
Aggregates of organized immune cells in organs that were the original site of infection.
TH1 subset
See T helper type 1 (TH1) cells.
TH2 subset
See T helper type 2 (TH2) cells.
Thoracic duct
The largest of the lymphatic vessels. It returns lymph to the circulation by emptying into the left subclavian vein near the heart.
Thromboxane
Lipid inflammatory mediator derived from arachidonic acid.
Thymic cortex
The outer region of the thymic organ that is just under the capsule. This is populated by cortical thymic epithelial cells and immature double-positive (CD4+CD8+) thymocytes. It is the major site of positive selection.
Thymic medulla
The inner region of the thymic organ that is populated by medullary thymic epithelial cells and mature, single-positive (CD4+ or CD8+) thymocytes. It is the major site of negative selection against tissue-specific antigens.
Thymic T REG (tTREG) cells
A T-cell subset that is induced to express FoxP3 and acquires regulatory function during development in the thymus, and is responsible for suppressing immune activity against specific antigen. See also Peripheral TREG (pTREG) cells.
Thymocytes
Developing T cells present in the thymus.
Thymus
A primary lymphoid organ, in the thoracic cavity, where T-cell maturation takes place.
Thymus-dependent (TD) antigen
Antigen that is unable to stimulate B cells to antibody production in the absence of help from T cells; response to such antigens involves isotype switching, affinity maturation, and memory-cell production.
T-independent (TI) antigens
Antigens capable of eliciting a response from B cells in the absence of help from T cells.
TI-1 antigens
T-Independent antigens, Type 1. Antigens that are capable of eliciting an antibody response in the absence of T cell help. TI-1 antigens are capable of being mitogenic.
TI-2 antigens
T-Independent antigens, Type 2. Antigens that are capable of eliciting an antibody response in the absence of T cell help. TI-2 antigens are not capable of being mitogenic.
TIR domain
Toll-IL-1R domain. Cytoplasmic domain of the IL-1 receptor and TLRs. Also present in the adaptors MyD88 and TRIF, which interact with the receptors via TIR/TIR domain interactions.
Tissue typing
Refers to the determination of which MHC alleles are expressed or carried by an individual. The test for this (the “type” part of blood “type and matching”) can be either serologic, where the surface MHC allotypes are determined, or molecular, where probes are used to determine which MHC alleles are present in an individual. This assay is used to establish histocompatibility prior to transplantation of foreign tissues.
Titer
A measure of the relative strength of an antiserum. The titer is the reciprocal of the last dilution of an antiserum capable of mediating some measurable effect such as precipitation or agglutination.
TNF-α
Tumor Necrosis Factor α. A pro-inflammatory cytokine.
Tolerance
A state of immunologic unresponsiveness to particular antigens or sets of antigens. Typically, an organism is unresponsive or tolerant to self antigens.
Tolerogenic
A response that down-regulates immune activity.
Tolerogens
Antigens that induce tolerance rather than immune reactivity. See also immunogen.
Toll-like receptors (TLRs)
A family of cell-surface receptors found in invertebrates and vertebrates that recognize conserved molecules from many pathogens.
Toxoid
A toxin that has been altered to eliminate its ability to cause disease but that still can function as an immunogen in a vaccine preparation.
Trabeculae
Extensions of connective tissue (in this case, cartilage and bone) that provide a structural site and surface for the development of blood cells. Found at the ends of long bones (femur, tibia, humerus) as well as the edges of other bones.
TRAF6
TNF receptor-associated factor 6. Key signaling intermediate in IL-1R and TLR pathways. Activated by IRAK kinases and essential for activating downstream components.
Trafficking
The differential migration of lymphoid cells to and from different tissues.
Transcytosis
The movement of antibody molecules (polymeric IgA or IgM) across epithelial layers mediated by the poly-Ig receptor.
Transduce
To pass on a signal from one part of the cell or one signaling molecule to the next in a signaling cascade.
Transformation
Change that a normal cell undergoes as it becomes malignant, normally mediated by DNA alternations; also a permanent, heritable alteration in a cell resulting from the uptake and incorporation of foreign DNA into the genome.
Transforming growth factor-beta-kinase-1 (TAK1)
Protein kinase downstream of IL-1R, TLRs, and other pattern-recognition receptors; part of complex with TAB1, TAB2 that is activated by TRAF6 and phosphorylates the IKK complex.
Transfusion reaction
Type II hypersensitivity reaction to proteins or glycoproteins on the membrane of transfused red blood cells.
Transgene
A cloned foreign gene present in an animal or plant.
Transitional B cells (T1, T2)
Immature B cells that express the BCR but are not yet fully immunologically competent.
Transplantation
The process of moving an organ, tissue, or group of cells from one individual (donor) to another (recipient). The resulting tissue is sometimes called a “graft.”
TRIF
TIR-domain-containing adaptor protein. Adaptor recruited by TLR3 and TLR4 that mediates signaling pathway activating IRFs and interferon production.
T3 transitional B cells
B-cell stages in the spleen between bone marrow immature B cells and mature peripheral B cells. T1 cells express IgM and no/low levels of IgD and give rise to T2 cells, which express intermediate levels of IgD. Some enter follicles, where they give rise to mature B-2 cells; others enter the marginal zone and become MZ B cells. T3 cells express reduced levels of IgM and are anergic to self antigens.
Tuberculoid leprosy
A disease caused by the intracellular bacteria, Mycobacterium leprae and Mycobacterium lepromatosis, where the immune response successfully encapsulates the bacteria and prevents widespread tissue damage. This more controlled form of disease is associated with the production of a TH1 rather than TH2 response.
Tuft cells
Specialized sensory cells in the epithelium of mucosal tissues that play a role in the defense against worms; tuft cells are the sole source of IL-25.
Tumor necrosis factor (TNF) family
A family of cytokines whose members interact with trimeric cell-surface receptors and deliver a variety of signals to receptor-bearing cells, ranging from the induction of apoptosis to the elicitation of differentiation and cell division. They may be either soluble or membrane-bound.
Tumor-associated antigens (TSAs)
Antigens that are expressed on particular tumors or types of tumors that are not unique to tumor cells. They are generally absent from or expressed at low levels on most normal adult cells. Formerly referred to as tumor-associated transplantation antigens (TATAs).
Tumor-specific antigens (TSAs)
Antigens that are unique to tumor cells. Originally referred to as tumor-specific transplantation antigens (TSTAs).
Tumor-suppressor genes
Genes that encode products that inhibit excessive cell proliferation or survival. Mutations in these genes are associated with the induction of malignancy.
Two-photon microscopy
A type of microscopy that, like confocal microscopy, allows one to visualize fluorescent signals in one focal plane of a relatively thick tissue sample. It causes less damage than confocal microscopy and can be coupled with intravital imaging techniques.
Two-signal hypothesis
The proposal, now well established experimentally, that in order to be activated a naïve T cell must receive signals through its TCR (signal 1) as well as costimulatory receptors such as CD28 (signal 2).
Two-turn recombination signal sequences
Immunoglobulin gene recombination signal sequences separated by an intervening sequence of 23 base pairs.
Tyk
A kinase that belongs to the JAK family of kinases.
Type 1 diabetes (T1D)
An autoimmune disease caused by T-cell attack on the insulin-producing beta cells of the pancreas, necessitating daily insulin injections.
Type 1 responses
Immune responses to intracellular pathogens; they are typically dominated by TH1 and ILC1 lymphocytes, activate cytotoxic cells, and heighten phagocytic activity.
Type 2 responses
Immune responses to worms and some other extracellular pathogens; they are typically dominated by TH2 and ILC2 lymphocytes, as well as IgE and the cytokines IL-4, IL-5, and IL-13.
Type I hypersensitivity
A pathologic immune reaction to non-infectious antigens mediated by IgE. It is the basis for allergy and atopy.
Type I interferons
A group of cytokines belonging to the Interferon family of cytokines that mediates anti-viral effects. Type I interferons are released by many different cell types and are considered part of the innate immune system.
Type II hypersensitivity
A pathologic immune reaction to non-infectious antigens mediated by IgG and IgM, which recruit complement or cytotoxic cells. It underlies blood transfusion reactions, Rh factor responses, and some hemolytic anemias.
Type II interferon
A cytokine belonging to the interferon family that is normally secreted by activated T cells. Also known as Interferon ϓ.
Type III hypersensitivity
A pathologic immune reaction to non-infectious antigens mediated by antibody-antigen immune complexes. It underlies damage associated with several disorders, including rheumatoid arthritis and systemic lupus erythematosus.
Type III interferons
A subset of the Interferon family of cytokines, also known as lambda interferons (IFN-λ).
Type IV hypersensitivity
A pathologic immune reaction to non-infectious antigens mediated by T cells. It underlies the response to poison ivy.
Ubiquitin
A small signaling peptide that can either tag a protein for destruction by the proteasome, or, under some circumstances, activate that protein.
Ulcerative colitis
A form of inflammatory bowel disease (IBD) limited to the large intestine and characterized by an inappropriate type 2 response, accumulation of inflammatory cells, and damage to the epithelial layer.
Unproductive
An unproductive BCR or TCR gene rearrangement is one in which DNA recombination leads to a sequence containing a stop codon, that cannot therefore be transcribed and translated to form a functional protein.
Upper respiratory tract
That part of the respiratory system that includes the mouth, trachea, and major bronchi.
Upstream
(1) Towards the 5′ end of a gene; (2) Closer to the receptor in a signaling cascade.
V (variable) gene segment
The 5′ coding portion of rearranged immunoglobulin and T-cell receptor genes. There are multiple V gene segments in germ-line DNA, but gene rearrangement leaves only one segment in each functional gene.
V (D)J recombinase
The set of enzymatic activities that collectively bring about the joining of gene segments into a rearranged V(D)J unit.
Vaccination
Intentional administration of a harmless or less harmful form of a pathogen in order to induce a specific adaptive immune response that protects the individual against later exposure to the pathogen.
Vaccine
A preparation of immunogenic material used to induce immunity against pathogenic organisms.
Valence, valency
Numerical measure of combining capacity, generally equal to the number of binding sites. Antibody molecules are bivalent or multivalent, whereas T-cell receptors are univalent.
Variability
(Antibody) variability is defined by the number of different amino acids at a given position divided by the frequency of the most common amino acid at that position.
Variable (V) region
Amino-terminal portions of immunoglobulin and T-cell receptor chains that are highly variable and responsible for the antigenic specificity of these molecules.
Variable (VL)
The variable region of an antibody light chain.
Vascular addressins
Tissue-specific adhesion molecules that direct the extravasation of different populations of circulating lymphocytes into particular lymphoid organs.
Vascular niche
Microenvironment in the bone marrow that fosters the development of hematopoietic stem cells and is postulated to associate specifically with hematopoietic stem cells that have begun to differentiate into mature blood cells.
Vector-borne infections
Infections that are transmitted to their hosts via an intermediate vector species, such as a mosquito, tick, or fly.
Villi
Folds in the wall of the intestinal tract that enhance the surface area of the intestinal lining.
Viral load
Concentration of virus in blood plasma; usually reported as copies of viral genome per unit volume of plasma.
Viral oncogene
Any cancer-promoting sequence carried by a virus that can induce transformation in infected host cells.
VpreB
A polypeptide chain that together with λ5 forms the surrogate light chain of the pre-B-cell receptor.
Western blotting
A common technique for detecting a protein in a mixture; the proteins are separated electrophoretically and then transferred to a polymer sheet, which is flooded with radiolabeled or enzyme-conjugated antibody specific for the protein of interest.
Wheal and flare reaction
A skin reaction to an injection of antigen that indicates an allergic response.
White pulp
Portion of the spleen that surrounds the arteries, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T cells.
Wiskott-Aldrich syndrome
An X-linked immune deficiency disorder caused by inheritance of a mutated WASP gene, which encodes a cytoskeletal protein highly expressed in hematopoietic cells and essential for proper immune synapse formation and intracellular signaling.
X-linked Hyper-IgM syndrome
An immunodeficiency disorder in which TH cells fail to express CD40L. Patients with this disorder produce IgM but not other isotypes, they do not develop germinal centers or display somatic hypermutation, and they fail to generate memory B cells.
X-linked severe combined immunodeficiency (X-SCID)
Immunodeficiency resulting from inherited mutations in the common ϓ chain of the receptor for IL-2, -4, -7, -9, and -15 that impair its ability to transmit signals from the receptor to intracellular proteins.
Xenograft
A graft or tissue transplanted from one species to another.
Yolk sac
Sac attached to the early embryo that provides nutrition for the embryo
Zymogen
A protein that is activated on proteolytic cleavage by a protease.