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114 C H A P T E R 4 Diseases of the Immune System                               Antibody-Mediated Diseases
                                                                                (Type II Hypersensitivity)
       IgE antibodies are produced in response to many helmin-
       thic infections, and their physiologic function is to target             Antibody-mediated (type II) hypersensitivity disorders are
       helminths for destruction by eosinophils and mast cells.                 caused by antibodies directed against target antigens on the
       Mast cells also are involved in defense against bacterial                surface of cells or other tissue components. The antigens
       infections. And snake aficionados will be relieved to hear               may be normal molecules intrinsic to cell membranes or in
       that their mast cells may protect them from some snake                   the extracellular matrix, or they may be adsorbed exoge-
       venoms by releasing granule proteases that degrade the                   nous antigens (e.g., a drug metabolite). Antibody-mediated
       toxins. Why these beneficial responses are inappropriately               abnormalities are the underlying cause of many human
       activated by harmless environmental antigens, giving rise                diseases; examples of these are listed in Table 4–3. In all of
       to allergies, remains a puzzle.                                          these disorders, the tissue damage or functional abnormali-
                                                                                ties result from a limited number of mechanisms.
          S U M M A RY
        Immediate (Type I) Hypersensitivity                                     Mechanisms of Antibody-Mediated Diseases

        •	 Also called allergic reactions, or allergies                         Antibodies cause disease by targeting cells for phagocyto-
        •	 Induced by environmental antigens (allergens) that stimu-            sis, by activating the complement system, and by interfer-
                                                                                ing with normal cellular functions (Fig. 4–10). The
             late strong TH2 responses and IgE production in geneti-            antibodies that are responsible typically are high-affinity
             cally susceptible individuals                                      antibodies capable of activating complement and binding
        •	 IgE coats mast cells by binding to Fcε receptors; reexpo-            to the Fc receptors of phagocytes.
             sure to the allergen leads to cross-linking of the IgE and         •	 Opsonization and phagocytosis. When circulating cells,
             FcεRI, activation of mast cells, and release of mediators.
        •	 Principal mediators are histamine, proteases, and other                 such as erythrocytes or platelets, are coated (opsonized)
             granule contents; prostaglandins and leukotrienes; and                with autoantibodies, with or without complement pro-
             cytokines.                                                            teins, the cells become targets for phagocytosis by
        •	 Mediators are responsible for the immediate vascular and                neutrophils and macrophages (Fig. 4–10, A). These
             smooth muscle reactions and the late-phase reaction                   phagocytes express receptors for the Fc tails of IgG anti-
             (inflammation).                                                       bodies and for breakdown products of the C3 comple-
        •	 The clinical manifestations may be local or systemic, and               ment protein, and use these receptors to bind and ingest
             range from mildly annoying rhinitis to fatal anaphylaxis.             opsonized particles. Opsonized cells are usually elimi-
                                                                                   nated in the spleen, and this is why splenectomy is of

Table 4–3  Examples of Antibody-Mediated Diseases (Type II Hypersensitivity)

Disease                     Target Antigen                                      Mechanisms of Disease                 Clinicopathologic
Autoimmune hemolytic        Red cell membrane proteins (Rh                      Opsonization and phagocytosis of      Manifestations
anemia                      blood group antigens, I antigen)                    erythrocytes                          Hemolysis, anemia
Autoimmune                  Platelet membrane proteins                          Opsonization and phagocytosis of      Bleeding
thrombocytopenic            (GpIIb/IIIa integrin)                               platelets
purpura                                                                                                               Skin vesicles (bullae)
Pemphigus vulgaris          Proteins in intercellular junctions                 Antibody-mediated activation of
                            of epidermal cells (epidermal                       proteases, disruption of              Vasculitis
Vasculitis caused by        desmoglein)                                         intercellular adhesions
ANCA                        Neutrophil granule proteins,                        Neutrophil degranulation and          Nephritis, lung hemorrhage
Goodpasture syndrome        presumably released from                            inflammation
                            activated neutrophils                                                                     Myocarditis
Acute rheumatic fever       Noncollagenous protein (NC1) in                     Complement- and Fc receptor–
                            basement membranes of kidney                        mediated inflammation                 Muscle weakness, paralysis
Myasthenia gravis           glomeruli and lung alveoli                                                                Hyperthyroidism
                            Streptococcal cell wall antigen;                    Inflammation, macrophage              Hyperglycemia, ketoacidosis
                            antibody cross-reacts with                          activation                            Abnormal myelopoiesis,
                            myocardial antigen                                                                        anemia
                            Acetylcholine receptor                              Antibody inhibits acetylcholine
                                                                                binding, downmodulates receptors
Graves disease              TSH receptor                                        Antibody-mediated stimulation of
(hyperthyroidism)                                                               TSH receptors
Insulin-resistant diabetes  Insulin receptor                                    Antibody inhibits binding of insulin
Pernicious anemia           Intrinsic factor of gastric parietal                Neutralization of intrinsic factor,
                            cells                                               decreased absorption of vitamin
                                                                                B12

ANCA, antineutrophil cytoplasmic antibodies; TSH, thyroid-stimulating hormone.
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