Ch. 43 The Body’s Defenses

The skin and mucous membranes provide first-line barriers to infection The first line of nonspecific defense consists of the intact skin and mucous membranes, mucus, ciliated cells lining the upper respiratory system, lysozyme, and gastric juices.

Phagocytic cells, inflammation, and antimicrobial proteins function early in infection The second line of nonspecific defense depends primarily upon neutrophils and macrophages, phagocytic white cells in the blood and tissues. Natural killer cells mediate lysis of virus-infected cells and tumor cells. Tissue damage triggers a local inflammatory response. Injured cells release histamine, a chemical signal that causes dilation and increased permeability of blood vessels, allowing fluid and large numbers of phagocytic white blood cells to enter the tissues. The most important antimicrobial proteins in the blood and tissues are the proteins of the complement system, involved in both nonspecific and specific defense, and interferons. Secreted by virus-infected cells, interferons inhibit virus production in neighboring cells.

HOW SPECIFIC IMMUNITY ARISES

Lymphocytes provide the specificity and diversity of the immune system A substance that elicits an immune response is called an antigen. The immune system recognizes specific antigens (molecules belonging to microbes, toxins, transplanted tissue, or cancer cells) and develops an immune response that inactivates or destroys that substance. B lymphocytes and T lymphocytes recognize antigens via surface antigen receptors: membrane antibodies for B cells, and T-cell receptors for T cells. Lymphocytes circulate throughout the blood and lymph and are found in high numbers in lymphatic tissues. The great diversity of lymphocytes, each with receptors of one particular specificity, gives the immune system the capacity to respond to virtually any antigen.

Antigens interact with specific lymphocytes, inducing immune responses and immunological memory Clonal selection occurs when an antigen activates a lymphocyte by binding to a specific receptor. In the primary immune response (to the body's first exposure to an antigen), the lymphocyte proliferates and differentiates, forming a clone of short-lived, infection-fighting effector cells and a clone of long-lived memory cells, all specific for the antigen. Secondary immune responses to that same antigen, which involve memory cells, are faster and often protective.

Lymphocyte development gives rise to an immune system that distinguishes self from nonself Lymphocytes develop from pluripotent stem cells in the bone marrow. B cells mature in the marrow, while T cells mature in the thymus. Self-tolerance develops as lymphocytes bearing receptors specific for native molecules are destroyed or rendered nonresponsive. Major histocompatibility complex (MHC) molecules are crucial to T cell function. Class I MHC molecules, located on all nucleated cells of the body, present antigen fragments to cytotoxic T cells. Class II MHC molecules, found mainly on macrophages and B cells, present antigen fragments to helper T cells. Developing T cells are exposed to class I and II MHC molecules on cells of the thymus. Only T cells bearing receptors with affinity for self-MHC molecules reach maturity.

IMMUNE RESPONSES

Helper T lymphocytes function in both humoral and cell-mediated immunity Humoral, or B cell, immunity, based on circulation of antibodies in the blood and lymph, defends against free viruses, bacteria, and other extracellular threats. Cell-mediated, or T cell, immunity defends against intracellular pathogens by destroying infected cells; it also defends against transplanted tissue and cancer cells. A CD4-bearing helper T cell is activated when its receptor binds specifically to a class II MHC-antigen complex on the surface of an antigen-presenting cell (APC). The T cell then secretes interleukin-2 and other cytokines, which help activate B cells and cytotoxic T cells.

In the cell-mediated response, cytotoxic T cells counter intracellular pathogens Most cytotoxic T cells are activated by cytokines and specific binding to class I MHC-antigen complexes on a target (infected, transplanted, or cancerous) cell. The T cell then secretes perforins, which form pores in the target cell membrane, causing the cell to lyse.

In the humoral response, B cells make antibodies against extracellular pathogens B cells are activated by cytokines and specific binding of their membrane antibodies to extracellular antigens. Most of these antigens are proteins or large polysaccharides, each with multiple epitopes. Antibodies, also called immunoglobulin (Ig) molecules, are serum proteins. The variable regions of an Ig molecule bind to a specific epitope; the constant regions determine the antibody's class. The five major immunoglobulin classes are IgG, IgM, IgA, IgD, and IgE. An antibody does not destroy an antigen directly but neutralizes it or targets it for elimination by opsonization, agglutination, precipitation, or complement fixation. Opsonization, agglutination, and precipitation enhance phagocytosis of the antigen-antibody complex; complement fixation leads to lysis of a complement protein-bound bacterium or virus.

Invertebrates have a rudimentary immune system Invertebrates have the ability to distinguish between self and nonself. In many invertebrates, amoeboid cells called coelomocytes can identify and destroy foreign substances. Experiments with earthworms show that their defense systems form memory against tissue grafts.

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IMMUNITY IN HEALTH AND DISEASE

Immunity can be achieved naturally or artificially Active immunity occurs when the immune system responds to a foreign antigen acquired either by natural infection or artificially, as by immunization. In immunization, a nonpathogenic form of a microbe or part of a microbe generates an immune response to and immunological memory for that microbe. Passive immunity occurs when antibodies are transferred from one individual to another. t occurs naturally, when IgG passes from mother to fetus or when IgA passes from mother to infant in breast milk, or artificially, when antibodies from an animal immune to a disease are injected into another animal, conferring short-term protection.

The immune system's capacity to distinguish self from nonself limits blood transfusion and tissue transplantation Certain antigens on red blood cells determine whether a person has type A, B, AB, or O blood. Antibodies to nonself blood types (generally IgM) already exist in the body. If incompatible blood is transfused, the transfused cells are killed by antibody- and complement-mediated lysis. The Rh factor, another red blood cell antigen, creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses. During delivery of the first Rh-positive infant, the mother's immune system develops anti-Rh IgG, which can cross the placenta and may attack the red blood cells of a subsequent Rh-positive fetus. The chances of success in organ or tissue transplantation are improved if the donor and recipient MHC tissue types are well matched. In addition, immunosuppressive drugs help prevent rejection. In bone marrow transplantation, there is danger of a graft versus host reaction.

Abnormal immune function can lead to disease In allergies such as hay fever, an allergen, such as pollen, triggers histamine release from mast cells, inducing vascular changes and typical symptoms. Sometimes the immune system loses tolerance for self, leading to autoimmune diseases such as rheumatoid arthritis and insulin-dependent diabetes. Some people are naturally deficient in humoral or cell-mediated immune defenses, or both.

AIDS is an immunodeficiency disease caused by a virus Acquired immunodeficiency syndrome (AIDS) is caused by the direct and indirect destruction of CD4-bearing T cells by HIV, the human immunodeficiency virus, over a period of years. AIDS, the final stage of this process, is marked by low helper T cell levels and opportunistic diseases characteristic of a deficient cell-mediated immune response.

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