CHAPTER 12 Effector Responses: Antibody- and Cell-Mediated Immunity

A colored micrograph shows two cytotoxic T lymphocytes on the surface of a cancer cell. — Two cytotoxic T lymphocytes bind to a tumor-specific antigen on the surface of a cancer cell, deliver the “kiss of death,” and induce apoptosis.

Learning Objectives

After reading this chapter, you should be able to:

Explain how humoral immune responses protect us against pathogens, toxins, or malignancy.
For antibody responses, recognize how the multiple immunoglobulin classes and subclasses can have common, but also distinct, mechanisms for antigen inactivation, elimination, tissue distribution, and other biological activities.
Describe the multistep process required for inducing the differentiation of T_C precursors into effector cytotoxic T lymphocytes (CTLs).
Compare and contrast the mechanisms by which CTLs and natural killer (NK) cells recognize and kill infected or tumor target cells.
Explain how NK cells and NKT cells each have some properties of innate immune cells and adaptive immune cells.

The previous chapters focused on how the immune response is initiated. Here, we will finally describe how the targets of the immune system—pathogens, infected cells, and even tumor cells—are actually cleared from the body.

We have already seen how the innate immune system initiates the response to a pathogen and alerts the adaptive immune system to the presence and nature of that pathogen (Chapter 4). In Chapters 8 through 11, we described the development and activation of the antigen-specific cells of the adaptive immune system, the B and T lymphocytes. You were also introduced to the differentiation and activity of helper T lymphocytes, a type of effector cell that regulates the activity and function of cytotoxic T cells, B cells, and other antigen-presenting cells. This chapter focuses on the effector molecules and cells of both the antibody-mediated (humoral) and cell-mediated immune responses that directly rid the organism of pathogens and abnormal cells. These effector responses are arguably the most important manifestations of immune responses: they rid the host both of foreign pathogens that have breached its innate defenses, as well as any of the host’s own cells that have become dangerous through infection or malignant transformation.

The humoral and cell-mediated branches of the immune system assume different, although overlapping, roles in clearing infection from a host. The effector molecules of the humoral branch are antibodies, the secreted versions of the highly specific membrane immunoglobulin receptors on the surface of B cells. Antibodies secreted into extracellular spaces and carried in the body secretions are exquisitely antigen specific and have several methods at their disposal to rid a body of pathogens. How an antibody contributes to clearing infection depends on its class (its heavy-chain isotype), which controls some of its effector functions, including whether it can recruit complement (recall Chapter 5). The class of an antibody also determines which receptors can bind it. Antibody-binding receptors, which bind the constant regions of antibodies and are therefore called Fc receptors or FcRs, determine which cells an antibody can activate to aid in its protective mission, as well as whether it can gain access to certain locations in the body.

If antibodies were the only agents of immunity, then intracellular pathogens (which occupy spaces that antibodies cannot access) and tumor cells would likely escape the immune system. Fortunately there is another effector branch of our immune system, cell-mediated immunity, which detects and kills cells that harbor intracellular pathogens or have otherwise become altered and potentially harmful. Cell-mediated immunity is carried out by helper T (CD4⁺ T_H) cells and several types of cytotoxic cells. As you saw in Chapter 10, T_H cells exert their effector functions indirectly, by contributing to the activation of antigen-presenting cells, B cells, and cytotoxic T cells via receptor-ligand interactions and soluble cytokines and chemokines. The functions of T_H cells in activating macrophages to kill their intracellular pathogens and to contribute to delayed-type hypersensitivity will be discussed in Chapter 15. On the other hand, cytotoxic cells exert their effector functions directly, by attacking infected cells and, in some cases, the pathogens themselves.

Effector cytotoxic cells arise from both the adaptive and innate immune systems and therefore include both antigen-specific and -nonspecific cells. Antigen-nonspecific (innate immune) cells that contribute to the clearance of infected cells include natural killer (NK) cells and myeloid cell types such as macrophages, neutrophils, and eosinophils. Antigen-specific cytotoxic cells include CD8⁺ cytotoxic T lymphocytes (CTLs or T_C cells), as well as the CD4⁺ NKT cell subpopulation, which, although derived from the T-cell lineage, displays some useful features of innate immune cell types, too. Even some populations of CD4⁺ T_H cells can be cytotoxic, producing cytokines that cause cell death.

The humoral and cell-mediated immune systems also cooperate effectively. Cells such as macrophages, neutrophils, eosinophils, and NK cells all express Fc receptors, which can induce phagocytosis of antibody-antigen complexes and/or the direct killing of target cells via a process known as antibody-dependent cell-mediated cytotoxicity.

In this chapter we will first focus on antibody-mediated effector functions, describing how they protect us from infections and how they get to certain sites in the body where they are needed. We will then describe the cytotoxic effector mechanisms mediated by cells of the innate and adaptive immune systems.

Last, the chapter also includes Clinical Focus, Advances, and Classic Experiment features. The Clinical Focus box describes how knowledge of antibody structure and function along with techniques for generating large amounts of homogeneous antibodies of desired specificities has led to a growing arsenal of therapeutic antibodies for a variety of conditions. The Advances box describes approaches that allow the detection, characterization, and isolation of antigen-specific T cells. The Classic Experiment box discusses recent findings showing that B and T lymphocytes are not the only cell types that can develop immunological memory; natural killer cells, members of the innate immune system, also have this capacity.