Fig. 5.14B ). Products of complement activation serve several functions (see Fig. 3.11, Chapter 3), one of which is to recruit neutrophils and monocytes, triggering inflammation in tissues. Leukocytes also may be activated by engagement of Fc receptors, which recognize the bound antibodies. Antibody-mediated inflammation is responsible for tissue injury in some forms of glomerulonephritis, vascular rejection in organ grafts, and other disorders.
• Antibody-mediated cellular dysfunction. In some cases, antibodies directed against a host protein impair or dysregulate important functions without directly causing cell injury or inflammation (
Fig. 5.14C ). In myasthenia gravis, antibodies against acetylcholine receptors in the motor end plates of skeletal muscles inhibit neuromuscular transmission, with resultant muscle weakness. Antibodies also can stimulate cellular responses excessively. In Graves disease, antibodies against the thyroid-stimulating hormone receptor stimulate thyroid epithelial cells to secrete thyroid hormones, resulting in hyperthyroidism. Antibodies against hormones and other essential proteins can neutralize and block the actions of these molecules, causing functional derangements.
Antigen–antibody (immune) complexes that are formed in the circulation may deposit in blood vessels, leading to complement activation and acute inflammation. Less
Table 5.5 Examples of Immune Complex–Mediated Diseases
SystemiclupuserythematosusNuclearantigens(circulatingor“planted”inkidney)Nephritis,skinlesions,arthritis,others
ReactivearthritisBacterialantigens(e.g.,Yersinia)Acutearthritis
SerumsicknessVariousproteins(e.g.,foreignserumprotein)(horseArthritis,vasculitis,nephritisanti-thymocyteglobulin) frequently, the complexes may be formed at sites where antigen has been “planted” previously (called in situ immune complexes). The antigens that form immune complexes may be exogenous, such as a foreign protein that is injected or produced by an infectious microbe, or endogenous, if the individual produces antibody against self antigens (autoimmunity). Examples of immune complex disorders and the antigens involved are listed in
Table 5.5 . Immune complex–mediated diseases tend be systemic, but often preferentially involve the kidney (glomerulonephritis), joints (arthritis), and small blood vessels (vasculitis), all of which are common sites of immune complex deposition.
Acute serum sickness is the prototype of a systemic immune complex disease; it was once a frequent sequela to the administration of large amounts of foreign serum (e.g., serum from immunized horses used for protection against diphtheria). In modern times, the disease is infrequent and usually seen in individuals who receive antibodies from other individuals or species, e.g. horse or rabbit antithymocyte globulin administered to deplete T cells in recipients of organ grafts. Nevertheless, it is an informative model that has taught us a great deal about immune complex disorders.
The pathogenesis of systemic immune complex disease can be divided into three phases (
Fig. 5.15
Formation of Immune Complexes. The introduction of a protein antigen triggers an immune response that results in the formation of antibodies, typically about 1 week after the injection of the protein. These antibodies are secreted into the blood, where they react with the antigen still present in the circulation and form antigen-antibody complexes.