Resistance to infectious agents is a requirement for survival in all species of animals. Characteristics of infectious agents, including virulence, route of entry, tissue tropism and ability to resist host defences, often influence the course of an infection. However, the species, breed, age and immunological competence of the host may also influence the progress of infection and, ultimately, its outcome. Although innate immune responses usually lack specificity and do not exhibit immunological memory, they constitute the first line of defence against invading microorganisms. The rate of response to infection by components of the innate immune system is relatively fast and offers protection against opportunistic pathogens. Cooperation between innate immunity and adaptive immunity is a requirement for protection against highly virulent pathogens which can resist phagocytosis and intracellular killing by macrophages and for microbial pathogens which elaborate potent toxins. Antibodies produced by B lymphocytes can neutralize viruses and bacterial toxins and, through the activity of IgA on mucosal surfaces, can protect the respiratory and alimentary tracts against microbial attack. The protective role of antibodies, however, is limited to extracellular pathogens as humoral immunity is ineffective against microbial and parasitic pathogens which replicate within host cells. Protection against intracellular pathogens including viruses, bacteria such as Mycobacterium bovis and Listeria monocytogenes and fungal pathogens such as Histoplasma capsulatum is dependent on effective cell-mediated immune responses which involve T helper cells and cytotoxic T lymphocytes. If, following intracellular infection by a microbial pathogen, the infected cells are unable to kill the invading agent, the only means of eradication of the infection is by destruction of the infected host cells. Accordingly, cell-mediated immunity is an essential part of adaptive immune responses to infectious agents.
Adaptive immunity can be divided into two branches, active immunity and passive immunity. Active immunity results from exposure to foreign antigenic material which activates B lymphocytes and T lymphocytes and induces an active immune response to the material encountered by the animal. Passive immunity refers to the transfer of antibodies from an actively immune animal to a susceptible animal. Antiserum specific for a particular pathogen or toxin can be administered by injection to give immediate short-term protection against infectious agents. Natural passive immunity is transmitted from dam to offspring through the ingestion of colostrum. Antibodies produced by the dam and secreted in colostrum passively protect newborn animals against a wide range of respiratory and enteric pathogens. These antibodies have the ability to neutralize bacterial toxins and viruses and can opsonize microbial pathogens for phagocytosis by macrophages and neutrophils. By activating the classical complement pathway, antibodies can opsonize pathogenic agents through fixation of C3b, leading to lysis of microbial pathogens.
Innate defences against bacterial invasion include epithelial barriers, mucociliary clearance of bacteria and inhibitory secretions such as gastric acid and bile. Although not considered part of innate defences, normal flora can compete with and sometimes prevent colonization by pathogenic microorganisms. Antimicrobial factors present in body fluids include complement, acute phase proteins, lysozyme and transferrin. Macrophages and neutrophils are two phagocytic cell types which are especially important in innate immunity (Box 13.1). The type of adaptive immune responses required for protection against a bacterial infection is determined by the virulence of the organism, tissue tropism and the pathogen's resistance to host defences. Cell-mediated immunity is essential for the control of intracellular bacteria such as Mycobacterium bovis and Listeria monocytogenes. Humoral immunity has a major protective role against extracellular bacteria. Secretory IgA can bind to bacterial adhesins and block bacterial attachment to mucosal surfaces. The presence of a capsule may render bacteria resistant to phagocytosis but when opsonized by specific antibody and C3b, such encapsulated bacteria can be ingested and destroyed by phagocytes. Specific antibody can agglutinate and immobilize motile bacteria, activate complement and neutralize bacterial toxins and enzymes which promote bacterial spreading in tissues (Box 13.2).
A relatively small number of fungal species cause disease in humans and animals. Tissue invasion by fungi is usually indicative of immunological incompetence, immunosuppression or, in the case of yeast infections, a consequence of prolonged antibacterial therapy. Innate defences offer the first and often the most important protection against many opportunistic fungal invaders. Intact skin, with its low pH and secreted fatty acids, and mucosal surfaces with their antimicrobial secretions are major barriers to fungal invasion. Competition from normal commensal microflora on the skin and on mucosal surfaces is important for its inhibitory effect on yeast proliferation on mucosal surfaces. Antimicrobial factors in body fluids, phagocytic cells and pathogen-recognition receptors on host cells provide both protection against fungal invasion and detection of their presence on mucosal surfaces (Box 13.3).
Adaptive immune responses to fungi involve cell-mediated immune responses and humoral responses. Although specific antibodies may opsonize fungal structures in host tissues and contribute to their clearance by neutrophils, protective immunity does not usually rely on humoral immune responses. Resistance to most fungal pathogens is dependent on T cell-mediated immunity, particularly CD4+ TH1 cells secreting interferon γ with the participation of macrophages, dendritic cells and natural killer (NK) cells (Box 13.4).
Induction of innate immune responses to viral infections result in the production of type I interferons and activation of NK cells. Type I interferons, a family of related polypeptides, include interferon (IFN)-α, IFN-β, IFN-κ and a number of other cytokines with similar biological activities. The stimulus for type I interferon synthesis is viral infection. Within hours of viral infection, IFN-α and IFN-β are produced by infected cells or by sentinel cells of the innate immune system. IFN-α is produced by leukocytes, especially macrophages, following viral infection. Fibroblast and epithelial cells produce IFN-β. Interferons bind to the interferon receptor on adjacent host cells and induce production of antiviral protein, enabling them to resist infection.
Within days of a viral infection, activated NK cells are present in the tissues. By killing host cells expressing viral antigen on their surfaces, NK cells contribute to the elimination of cellular reservoirs of infection. The ability of NK cells to protect host cells against infection is enhanced by cytokines secreted by macrophages and dendritic cells. Macrophages contribute to antiviral immunity through phagocytosis of viruses and virus-infected cells, sometimes with the involvement of specific antibody and complement (Box 13.5).
Innate immune responses to viral invasion are succeeded by adaptive immune responses. Antibodies, which block virus binding and entry into host cells, and cytotoxic T lymphocytes, which can eliminate infection by killing virus-infected cells, are the principal components involved in adaptive antiviral responses (Box 13.6). Antiviral antibodies function mainly as neutralizing antibodies which prevent virus attachment and entry into host cells. These antibodies bind to the viral envelope, capsid antigens and other surface antigenic components. Secreted antibodies of the IgA isotype prevent attachment of viruses to host cells on mucosal surfaces. Antibodies can promote clearance of virus particles from the circulation by clumping viruses and facilitating their removal by phagocytic cells. Lysis of some enveloped viruses by the membrane attack complex can occur when IgG or IgM antibodies bind to viral surface antigens and activate the complement system. In the course of a viral infection, CD8+ T cells undergo rapid proliferation. Expansion of the T-cell population is accompanied by differentiation into effector cytotoxic CD8+ T cells which release cytokines, particularly IFN-γ and tumour necrosis factor and kill infected cells directly through the release of perforin and granzymes.
Although the immune system has the ability to protect the host against a wide range of pathogenic microorganisms, the characteristics of individual infectious agents such as RNA viruses and retroviruses, with their high mutation rates, can limit the effectiveness of immune responses and long-lasting protection against some of these pathogens is difficult to achieve. The immune system itself is not exempt from defects, either developmental or acquired. Defects in one or more component of the immune system can result in increased susceptibility to opportunistic infections. A deficit affecting components of the immune system essential for the development of protective immunity invariably leads to overwhelming infection. A gradual decline in immunological competence of individual animals occurs as they approach the end of their normal lifespan.