Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

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the infected cell and are displayed on the target cell’s surface, where they are recognized by antigen receptors on the cytotoxic T cell (see Fig. 15-12). Cytotoxic T cells perform their killing function by releasing preformed cytotoxic proteins that induce apoptosis or programmed cell death of the target cell (see Chapter 2). The principal function of CD4 + cells of the T H 1 sub- set involves the defense against intracellular pathogens, such as mycobacteria, which grow primarily in phago- somes of macrophages, shielding them from the effects of both antibodies and cytotoxic T cells. These cells secrete the cytokine IFN- γ , a potent macrophage acti- vator, which stimulates the induction of microbicidal substances in macrophages, leading to the destruction of the ingested microbes. CD4 + T H 1 cells also produce a range of other cytokines, chemokines, and surface mol- ecules that do not activate infected macrophages, but instead kill chronically infected senescent macrophages, stimulate the production of new macrophages in bone marrow, and recruit fresh macrophages to sites of infec- tion. Thus, the CD4 + T H 1 cell controls and coordinates host defenses against certain intracellular pathogens, a function that helps to explain why a decreased CD4 + T H 1 count in persons with acquired immunodeficiency syndrome (AIDS) places them at high risk for intracel- lular pathogen infections. Active Versus Passive Immunity Adaptive, or specific, immune responses are designed to protect the body against potentially harmful foreign substances, infections, and other sources of non–self antigens. It is the specific protection that is acquired through exposure to antigens (active immunity) or through transfer of protective antibodies against an antigen (passive immunity). Active immunity is acquired through immunization or actually having a disease. It is called active immu- nity because it depends on a response to the antigen by the person’s immune system. Active immunity, although long lasting once established, requires a few days to weeks after a first exposure before the immune response is sufficiently developed to contribute to the destruction of the pathogen. However, the immune system usually is able to react within hours to subsequent exposure to the same agent because of the presence of memory B and T lymphocytes and circulating antibodies. The process of acquiring the ability to respond to an antigen after its administration by vaccine is known as immunization. An acquired immune response can improve on repeated exposures to an injected antigen or a natural infection. Passive immunity is immunity transferred from another source. An infant receives passive immunity naturally from the transfer of antibodies from its mother in utero and through breast milk. Maternal IgG crosses the placenta and protects the newborn during the first few months of life. Normally, an infant has few infec- tious diseases during the first 3 to 6 months owing to the protection provided by the mother’s antibodies. Passive immunity also can be artificially provided by the

transfer of antibodies produced by other people or ani- mals. Some protection against infectious disease can be provided by the injection of hyperimmune serum, which contains high concentrations of antibodies for a specific disease, or immune serum or gamma globulin, which contains a pool of antibodies from many individuals providing protection against many infectious agents. Passive immunity produces only short-term protection that lasts weeks to months.

Regulation of the Immune Response

Self-regulation is an essential property of the immune system. An inadequate immune response may lead to immunodeficiency, but an inappropriate or excessive response may lead to conditions varying from allergic reactions to autoimmune diseases. This regulation is not well understood and involves all aspects of the immune response—antigen, antibody, cytokines, regulatory T cells, and the neuroendocrine system. With each exposure to antigen, the immune systemmust determine the branch of the immune system to be activated and the extent and duration of the immune response. After exposure to an antigen, the immune response to that antigen develops after a brief lag, reaches a peak, and then recedes. Normal immune responses are self-limited because the response eliminates the antigen, and the prod- ucts of the response, such as cytokines and antibodies, have a limited life span and are secreted only for brief periods after antigen recognition. Evidence suggests that cytokine feedback from the helper T or regulatory T cells controls several aspects of the immune response. Another facet of immune self-regulation is inhibition of immune responses by tolerance. The term tolerance is used to define the ability of the immune system to be nonreactive to self-antigens while producing immunity to foreign agents. Tolerance to self-antigens protects an individual from harmful autoimmune reactions (see Chapter 16). Exposure of an individual to foreign anti- gens may lead to tolerance and the inability to respond to potential pathogens that cause infection. Tolerance exists not only to self-tissues but also to maternal–fetal tissues. Special regulation of the immune system is evi- dent in privileged sites such as the brain, testes, ovaries, and eyes. Immune damage in these areas could result in serious consequences to the individual and the species.

SUMMARY CONCEPTS

■■ The adaptive immune response involves a complex series of interactions between components of the immune system and the antigens of a foreign pathogen. It is able to distinguish between self and nonself, recognize and specifically react to large numbers of