Chapter 19: Hypersensitivity Disorders Remember: hypersensitivity responses can occur against a self antigens (autoimmunity), environmental antigens, and microbes. Unfortunately, many hypersensitivity disorders are chronic. Please see Table 19-1 on page 400 for a summary of the hypersensitivity diseases, their mechanism of action, as well as the immune components involved. Type II Hypersensitivities (Antibody-Mediated Disease) This reaction is initiated when: If the antibody binds to: Here are a few examples: Example: Abbas, Lichtman and Pillai8_Figure 19-2; p.402Example: Abbas, Lichtman and Pillai8_Figure 19-2; p.402Table 19-2: Examples of Diseases Caused by Cell- or Tissue-Specific Antibodies (Abbas, Lichtman and Pillai, 8th Ed.; p.403) Disease Target Antigen Mechanisms of Disease Clinicopathologic Manifestations Autoimmune hemolytic anemia Erythrocyte membrane proteins Opsonization and phagocytosis of erythrocytes, complement-mediated lysis Hemolysis, anemia Autoimmune thrombocytopenic purpura Platelet membrane proteins (gpIIb-IIIa integrin) Opsonization and phagocytosis of platelets Bleeding Pemphigus vulgaris Proteins in intercellular junctions of epidermal cells (desmoglein) Antibody-mediated activation of proteases, disruption of intercellular adhesions Skin vesicles (bullae) Vasculitis caused by ANCA Neutrophil granule proteins, presumably released from activated neutrophils Neutrophil degranulation and inflammation Vasculitis Goodpasture’s syndrome Non-collagenous NC1 protein of basement membrane in glomeruli and lung Complement- and Fc receptor–mediated inflammation Nephritis, lung hemorrhage Acute rheumatic fever Streptococcal cell wall antigen; antibody cross-reacts with myocardial antigen Inflammation, macrophage activation Myocarditis, arthritis Myasthenia gravis Acetylcholine receptor Antibody inhibits acetylcholine binding, downmodulates receptors Muscle weakness, paralysis Graves’ disease (hyperthyroidism) TSH receptor Antibody-mediated stimulation of TSH receptors Hyperthyroidism Insulin-resistant diabetes Insulin receptor Antibody inhibits binding of insulin Diabetes mellitus Pernicious anemia Intrinsic factor of gastric parietal cells Neutralization of intrinsic factor; decreased absorption of vitamin B12 Abnormal erythropoiesis, anemia, neurologic symptomsType III Hypersensitivities (Immune Complex-Mediated Disease) In this response, antibodies are binding to Serum Sickness Abbas, Lichtman and Pillai8_Figure 19-1B; p.401 Abbas, Lichtman and Pillai8_Figure 19-4; p.405TABLE 19-3: Examples of Human Immune Complex–Mediated Diseases (From Abbas, Lichtman and Pillai, 8th Edition; p.406) Disease Antigen Involved Clinicopathologic Manifestations Systemic lupus erythematosus DNA, nucleoproteins, others Nephritis, arthritis, vasculitis Polyarteritis nodosa Hepatitis B virus surface antigen (in some cases) Vasculitis Post-streptococcal glomerulonephritis Streptococcal cell wall antigens Nephritis Serum sickness Various proteins Arthritis, vasculitis, nephritis Type IV Hypersensitivities (T Cell Mediated Delayed Hypersensitivity) This hypersensitivity response is mediated by: Here, the target antigen may be: Abbas, Lichtman and Pillai8_Figure 19-5; p.406TABLE 19-4: T Cell–Mediated Diseases (From Abbas, Lichtman and Pillai, 8th Edition; p.407) Disease Specificity of Pathogenic T Cells Principal Mechanisms of Tissue Injury Rheumatoid arthritis Collagen? Citrullinated self proteins? Inflammation mediated by TH1 and TH17 cytokines Role of antibodies and immune complexes? Multiple sclerosis Protein antigens in myelin (e.g., myelin basic protein) Inflammation mediated by TH1 and TH17 cytokines Myelin destruction by activated macrophages Type 1 diabetes mellitus Antigens of pancreatic islet β cells (insulin, glutamic acid decarboxylase, others) T cell–mediated inflammation Destruction of islet cells by CTLs Inflammatory bowel disease Enteric bacteria Self antigens? Inflammation mediated by TH1 and TH17 cytokines Psoriasis Unknown skin antigens Inflammation mediated by T cell–derived cytokines Examples of human T cell–mediated diseases are listed. In many cases, the specificity of the T cells and the mechanisms of tissue injury are inferred on the basis of the similarity with experimental animal models of the diseases. The roles of TH1 and TH17 cells have been inferred from experimental models and the presence of subset-specific cytokines in human lesions. The cytokines may be produced by cells other than CD4+ T lymphocytes. Ongoing clinical trials targeting these cytokines may provide new information about the contributions of the cytokines in different diseases. Abbas, Lichtman and Pillai8_Figure 19-5; p.406Contact Hypersensitivity Responses Delayed-Type Hypersensitivities Abbas, Lichtman and Pillai8_Figure 19-6; p.408Chronic T cell activation leads to granuloma formation Abbas, Lichtman and Pillai8_Figure 19-8;