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    Chapter43.doc Chapter43.doc Document Transcript

    • Chapter 43: The Body’s Defenses I. An overview of the body’s three lines of defense (fig. 43.1) A. First line–protective barriers (nonspecific) B. Second line–phagocytosis and inflammatory response (nonspecific) C. Third line–immune system (specific) II. Nonspecific defenses against infection A. First line of defense 1. External barrier (skin and mucous membrane; fig. 43.2) 2. Secretion of chemicals a. Sweat, saliva, tears (contain lysozymes) b. Acidic environment of stomach B. Second line of defense 1. Phagocytic and natural killer cells a. Neutrophils (60-70% of WBCs) b. Monocytes (5% of WBCs)–develop into large macrophages that may be motile or reside permanently in specific tissues c. Eosinphils (1.5% of WBCs) d. Natural killer cells–cause infected cells to lyse 2. Inflammatory response (fig. 43.5) a. Initiated by chemical signals i. Basophils and mast cells release histamine
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 ii. Leukocytes and damaged tissue cells release prostaglandins b. Increase in local blood supply and capillary permeability i. Edema (swelling) ii. Blood clotting c. Release of chemokines attracts phagocytic cells i. Phagocytose pathogens and clean up damaged tissue ii. Pus formation d. Severe tissue damage elicits a systemic response i. Large increase in blood leukocytes ii. Fever (often triggered by release of pyrogens) iii. Occasionally leads to septic shock 3. Antimicrobial proteins a. Lysozymes b. Complement system–set of about 20 serum proteins c. Interferons–inhibit spread of viral infection III. Overview of immune response (third line of defense) A. Important differences between specific and nonspecific immunity 1. Specificity 2. Diversity 3. Memory 4. Self/nonself recognition Page 2
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 B. Mediated by lymphocytes 1. B lymphocytes (B cells)–humoral immune response a. Form and mature in bone marrow (fig. 43.8) b. Secrete antibodies 2. T lymphocytes (T cells)–cell-mediated immune response a. Form in bone marrow; mature in thymus (fig. 43.8) b. Cytotoxic T cells (TC cells)–attack infected cells c. Helper T cells (TH cells)–coordinate immune response C. Specificity of immune system 1. Antigen–foreign molecule that elicits a specific response by lymphocytes 2. Antigen receptor–plasma membrane bound receptors a. Highly specific! b. ≈ 100,000 identical antigen receptors per lymphocyte c. Membrane receptors (B cells) d. T cell receptors (T cells) 3. Antibody–antigen binding protein (immunoglobulin) secreted by B cells D. Diversity of immune system 1. Arises early in development BEFORE antigen exposure 2. Millions of different B cells and T cells are generated E. Immunological memory (fig. 43.7) 1. Clonal selection–selective antigen-driven cloning of lymphocytes (fig. 43.6) a. Effector cells–short-lived cells that combat antigen Page 3
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 i. Effector T cells ii. Plasma cells (secrete antibodies) b. Memory cells–long-lived cells bearing receptors specific for same antigen c. Leads to both amplification and memory 2. Primary immune response–triggered by first-time antigen exposure 3. Secondary immune response–triggered by repeated antigen exposure F. Ability of immune system to distinguish self from nonself 1. Maturing lymphocytes tested for potential self-reactivity a. Self-reactive cells destroyed b. Leads to self-tolerance 2. Major histocompatibility complex (MHC) molecules a. MHC molecules–collection of cell surface glycoproteins that mark cells as “self” b. Encoded by a multigene family c. Class I MHC molecules–found on virtually all nucleated cells d. Class II MHC molecules–found on macrophages, B cells and activated T cells e. Collection of cell surface MHC molecules is unique to each individual f. Function of MHC molecules is antigen presentation (fig. 43.9) i. TC cells recognize Class I MHC molecule/antigen complexes ii. TH cells recognize Class II MHC molecule/antigen complexes g. Family of MHC molecules can present a variety of antigen fragments 3. Antigen presentation=combination of self (MHC molecule) and nonself (antigen fragment) Page 4
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 IV. Immune response A. Two lines of attack (fig. 43.10) 1. Humoral immunity–B cells (antibodies) attack antigens in body fluid 2. Cell-mediated immunity–TC cells attack cells infected by antigens B. Helper T cells coordinate immune response 1. Activation of TH cells (fig. 43.11) a. Antigen presenting cells (APCs) require class II MHC molecules (e.g., macrophages or B cells) b. CD4 stabilizes interaction between TH cell and APC c. Macrophage releases a cytokine called interleukin-1 (IL-1) d. Activated TH cell undergoes clonal selection 2. Clone of activated TH cells secrete several different cytokines a. Interleukin-2 (IL-2)–facilitates clonal selection of B, TC and TH cells b. IL-2 also stimulates same TH cell (positive feedback) c. Secretion of IL-2 required to activate most B cells and all TC cells C. Cell-mediated immunity (TC cells) 1. Activation of TC cells (fig. 43.12) a. Antigen presenting cells require class I MHC molecules b. CD8 stabilizes interaction between TC cell and APC c. TC cell further stimulated by release of IL-2 from nearby TH cell 2. Activated TC cell undergoes clonal selection a. Effector T cell = active killer Page 5
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 b. Kills target cell by releasing perforin 3. TC cells attack tumor cells and transplanted tissue cells in similar manner 4. Natural killer (NK) cells provide system with redundancy D. Humoral immunity 1. TH cell mediated activation of B cells (fig. 43.13) a. Triggered by T-dependent antigens b. Membrane receptors of B cell bind to T-dependent antigens c. B cells further stimulated by release of IL-2 from nearby TH cell d. Activated B cell undergoes clonal selection e. Clone of plasma cells secrete antibodies (≈ 2000 antibody molecules/sec) 2. Independent activation of B cells a. Triggered by T-independent antigens b. Activation of B cells occurs in the absence of IL-2 c. No memory cells generated 3. NOTE: B CELLS CAN ALSO ACT AS ANTIGEN PRESENTING CELLS V. Role of antibodies A. Antibody structure 1. Y-shaped protein consisting of two heavy chains and two light chains (fig. 43.15) 2. Epitope–small portion of antigen molecule with which antibody interacts (fig. 43.14) 3. Contains two identical, highly specific antigen-binding sites (variable regions) 4. Monoclonal vs. polyclonal antibodies Page 6
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 5. Antibodies = immunoglobulins (Igs) = globular proteins a. Five major classes (IgM, IgG, IgA, IgD and IgE) b. Tail of antibody (constant region) determines class (table 43.1) B. Antibody-mediated disposal of antigen (fig. 43.16) 1. Inactivation and opsonization (enhancement of phagocytosis by macrophages) a. Neutralization–antibody binds to and blocks activity of antigen b. Antibody-mediated agglutination (clumping) c. Precipitation–cross-linking of soluble antigen molecules 2. Complement fixation (activation of complement system) a. Involves a cascade of activation steps that results in lysis of pathogenic cell by membrane attack complex (MAC) b. Classical pathway–antibody dependent (fig. 43.17) c. Alternate pathway–antibody independent (nonspecific response) d. Activated complement proteins also contribute to inflammation 3. Importance of positive feedback: antibodies –> phagocytosis –> antigen presentation –> activation of TH cells –>stimulation of all lymphocytes! VI. Immunity in health and disease A. Active vs. passive immunity 1. Active immunity–immunity conferred by recovery from an infectious disease a. Depends on response by person’s own immune system b. May be acquired naturally or artificially (vaccination/immunization) Page 7
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 c. Results in immunological memory 2. Passive immunity–immunity transferred from one individual to another a. Examples: pregnancy, nursing b. Offers short-term, immediate protection B. Immunity, blood transfusions and tissue transplantations 1. ABO blood groups a. Type A = A antigens b. Type B = B antigens c. Type AB = A and B antigens d. Type O = no antigens 2. Rh factor (Rh-positive = Rh antigen is present) 3. Tissue grafts and organ transplantation a. Foreign MHC molecules lead to rejection (immune response) b. Tissue matching and use of immunosuppressive drugs c. Bone marrow transplants–graft vs. host reaction C. Abnormal immune function 1. Allergy–hypersensitive response to environmental allergen (fig. 43.18) a. Typically involve IgE antibodies b. Allergens interact with IgE antibodies bound to mast cells ( c. Induces degranulation of mast cells and thus histamine release 2. Anaphylactic shock–life-threatening reaction to injected or ingested allergens 3. Autoimmune diseases Page 8
    • Chapter 43: The Body’s Defenses 1/8/04-1/13/04 a. Immune system turns against bodies own molecules/cells (auto-antibodies) b. Examples: lupus, rheumatoid arthritis, Type I diabetes, multiple sclerosis 4. Immunodeficiency diseases a. May affect humoral immunity, cell-mediated immunity, or both (SCID) b. Many kinds; may be inborn or acquired 5. AIDS–acquired immunodeficiency syndrome (fig. 43.20) a. Makes people very susceptible to opportunistic diseases b. HIV (human immunodeficiency virus)–retrovirus that causes AIDS by infecting cells bearing surface CD4 molecules (e.g., TH cells) c. HIV-positive = anti-HIV antibodies are present in blood Hmm.... This would make an excellent exam question! Clearly explain how the immune system is able to distinguish between self and nonself (i.e., cells of the body versus foreign cells and microbes). Be sure to discuss the role of MHC molecules. Why don’t cytotoxic T cells destroy healthy body cells? Page 9