Autoimmune dysfunctions similar to certain human autoimmune diseases can be induced experimentally in some animals (see Table 20-2). One of the first such animal models was discovered serendipitously in 1973 when rabbits were immunized with acetylcholine receptors purified from electric eels. The animals soon developed muscular weakness similar to that seen in myasthenia gravis. This experimental autoimmune myasthenia gravis (EAMG) was shown to result when antibodies to the acetylcholine receptor blocked muscle stimulation by acetylcholine in the synapse. Within a year, this animal model had proved its value with the discovery that auto-antibodies to the acetylcholine receptor were the cause of myasthenia gravis in humans.
Experimental autoimmune encephalomyelitis (EAE) is another animal model that has greatly improved understanding of autoimmunity. This is one of the best-studied models of autoimmune disease. EAE is mediated solely by T cells and can be induced in a variety of species by immunization with myelin basic protein (MBP) or proteolipid protein (PLP) in complete Freund's adjuvant (Figure 20-7). Within 2-3 weeks the animals develop cellular infiltration of the myelin sheaths of the central nervous system, resulting in demyelination and paralysis. Most of the animals die, but others have milder symptoms, and some animals develop a chronic form of the disease that resembles chronic relapsing and remitting MS in humans. Those that recover are resistant to the development of disease from a subsequent injection of MBP and adjuvant.
The mouse EAE model provides a system for testing treatments for human MS. For example, because MBP- or PLP-specific T-cell clones are found in the periphery, it is assumed that these clones must have escaped negative selection in the thymus. Recent mouse experiments have suggested that orally administered MBP may make these antigen-specific peripheral T-cell clones self-tolerant. These studies have paved the way for clinical trials in MS patients.
Experimental autoimmune thyroiditis (EAT) can be induced in a number of animals by immunizing with thy-roglobulin in complete Freund's adjuvant. Both humoral antibodies and TH1 cells directed against the thyroglobulin develop, resulting in thyroid inflammation. EAT appears to best mimic Hashimoto's thyroiditis. In contrast to both EAE and EAT, which are induced by immunizing with self-antigens, autoimmune arthritis (AA) is induced by immunizing rats with Mycobacterium tuberculosis in complete Freund's adjuvant. These animals develop an arthritis whose features are similar to those of rheumatoid arthritis in humans.
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