Experimental Models of Immune Complex Mediated Diseases

Serum Sickness

Much of our current knowledge of immune complex diseases is based on analyses of experimental models of

FIGURE 18-4 Sequence of immunologic responses in experimental acute serum sickness. Injection of bovine serum albumin into a rabbit leads to the production of specific antibody and the formation of immune complexes. These complexes are deposited in multiple tissues, activate complement (leading to a fall in serum complement levels), and cause inflammatory lesions, which resolve as the complexes and the remaining antigen are removed and free antibody (not bound to antigen) appears in the circulation (Adapted from Cochrane CG. Immune complex-mediated tissue injury. In Cohen S, PA Ward, and RT McCluskey [eds]. Mechanisms of Immunopathology. Werbel & Peck, New York, 1979, pp 29-48. ©1979, Wiley-Liss, Inc.)

FIGURE 18-4 Sequence of immunologic responses in experimental acute serum sickness. Injection of bovine serum albumin into a rabbit leads to the production of specific antibody and the formation of immune complexes. These complexes are deposited in multiple tissues, activate complement (leading to a fall in serum complement levels), and cause inflammatory lesions, which resolve as the complexes and the remaining antigen are removed and free antibody (not bound to antigen) appears in the circulation (Adapted from Cochrane CG. Immune complex-mediated tissue injury. In Cohen S, PA Ward, and RT McCluskey [eds]. Mechanisms of Immunopathology. Werbel & Peck, New York, 1979, pp 29-48. ©1979, Wiley-Liss, Inc.)

serum sickness. Immunization of an animal such as a rabbit with a large dose of a foreign protein antigen leads to the formation of antibodies against the antigen (Fig. 18-4). These antibodies bind to and form complexes with circulating antigen, which are initially cleared by macrophages in the liver and spleen. As more and more antigen-antibody complexes are formed, some of them are deposited in vascular beds. In these tissues, the antibodies in the complexes may activate complement, with a concomitant fall in serum complement levels. Complement activation leads to recruitment and activation of inflammatory cells, predominantly neutrophils, at the sites of immune complex deposition, and the neutrophils cause tissue injury. Neutrophils also bind to the immune complexes by their Fcy receptors, and Fc receptor signaling activates the leukocytes to produce substances that damage tissues, as in diseases caused by antibodies against fixed tissues. Because the complexes are deposited mainly in small arteries, renal glomeruli, and the synovia of joints, the clinical and pathologic manifestations are vas-culitis, nephritis, and arthritis. The clinical symptoms are usually short-lived, and the lesions heal unless the antigen is injected again. This type of disease is an example of acute serum sickness. A more indolent and prolonged disease, called chronic serum sickness, is produced by multiple injections of antigen, which lead to the formation of smaller complexes that are deposited most often in the kidneys, arteries, and lungs.

Arthus Reaction

A localized form of experimental immune complex-mediated vasculitis is called the Arthus reaction. It is induced by injection of an antigen subcutaneously into a previously immunized animal or an animal that has been given intravenous antibody specific for the antigen. Circulating antibodies rapidly bind to the injected antigen and form immune complexes that are deposited in the walls of small arteries at the injection site. This deposition gives rise to a local cutaneous vasculitis with tissue necrosis. This model has been used to study the cells and molecules involved in immune complex diseases.

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