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Hypersensitivity Reactions: Mechanisms of Immune-Mediated Injury 115

Opsonization and phagocytosis

Opsonized                Fc receptor                                                                         Phagocytosed
         cell                                                                                                cell
                                                                                           Phagocytosis
C3b

                                 C3b     Phagocyte
                               receptor

A Complement activation

Complement- and Fc receptor–mediated inflammation

                     Fc                                        Complement   Neutrophil
              receptor                                                      enzymes,
                                                               by-products
B                                                              (C5a, C3a) reactive oxygen
                                                                            intermediates

                               Complement activation                                   Inflammation and tissue injury

Antibody-mediated cellular dysfunction                                          Nerve
                                                                               ending
      Antibody                           TSH                     Antibody to                              Acetylcholine
        against                          receptor              ACh receptor                               (ACh)

TSH receptor                                                                                                ACh
                    Thyroid                                                                                 receptor

                  epithelial
                         cell

                                                               Muscle

                                   Thyroid hormones                         Antibody inhibits binding of
                                                                            neurotransmitter to receptor
C Antibody stimulates receptor without hormone

Figure 4–10  Mechanisms of antibody-mediated injury. A, Opsonization of cells by antibodies and complement components, and ingestion of opso-
nized cells by phagocytes. B, Inflammation induced by antibody binding to Fc receptors of leukocytes and by complement breakdown products.
C, Antireceptor antibodies disturb the normal function of receptors. In these examples, antibodies against the thyroid-stimulating hormone (TSH)
receptor activate thyroid cells in Graves disease, and acetylcholine (ACh) receptor antibodies impair neuromuscular transmission in myasthenia gravis.

   clinical benefit in autoimmune thrombocytopenia and            responses excessively. In Graves disease, antibodies
   some forms of autoimmune hemolytic anemia.                     against the thyroid-stimulating hormone receptor stim-
•	 Inflammation. Antibodies bound to cellular or tissue anti-     ulate thyroid epithelial cells to secrete thyroid hormones,
   gens activate the complement system by the “classical”         resulting in hyperthyroidism. Antibodies against hor-
   pathway (Fig. 4–10, B). Products of complement activa-         mones and other essential proteins can neutralize and
   tion serve several functions (see Fig. 2–18, Chapter 2),       block the actions of these molecules, causing functional
   one of which is to recruit neutrophils and monocytes,          derangements.
   triggering inflammation in tissues. Leukocytes may also
   be activated by engagement of Fc receptors, which rec-      Immune Complex Diseases
   ognize the bound antibodies. This mechanism of injury       (Type III Hypersensitivity)
   is exemplified by Goodpasture syndrome and pemphi-
   gus vulgaris.                                               Antigen–antibody (immune) complexes that are formed in the
•	 Antibody-mediated cellular dysfunction. In some cases,      circulation may deposit in blood vessels, leading to complement
   antibodies directed against cell surface receptors impair   activation and acute inflammation. The antigens in these com-
   or dysregulate cellular function without causing cell       plexes may be exogenous antigens, such as microbial pro-
   injury or inflammation (Fig. 4–10, C). In myasthenia        teins, or endogenous antigens, such as nucleoproteins. The
   gravis, antibodies against acetylcholine receptors in       mere formation of immune complexes does not equate
   the motor end plates of skeletal muscles inhibit            with hypersensitivity disease; small amounts of antigen–
   neuromuscular transmission, with resultant muscle           antibody complexes may be produced during normal
   weakness. Antibodies can also stimulate cellular
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