Myasthenia gravis is a spontaneously occurring autoimmune disease in which antibodies and lymphocytes are specifically reactive with nicotinic ACh receptors of skeletal muscle. Antibodies reactive with junctional receptors of human muscle are found in 90% of patients with myasthenia gravis and not at all in other diseases. Their capacity to cross the placenta suggests their involvement in the pathogenesis of neonatal myasthenia. The role of the thymus in myasthenia gravis remains a mystery, but it has recently been established that the thymus contains nicotinic ACh receptors and that anti-receptor antibodies are present in myasthenic thymuses. Antibodies of myasthenic patients detect only partial cross reactivity between ACh receptors of different species. However, greater antibody binding is observed with receptors isolated from denervated rat muscle than with receptors from normal rat muscle. This suggests that extrajunctional and junctional ACh receptors might express different antigenic determinants. Although human antibodies bind minimally to ACh receptors of the electric organs of eels and marine rays, lymphocyte reactivity to electric eel receptors is found in high incidence in myasthenic patients. This suggests that electric organ and mammalian muscle ACh receptors may share more lymphocyte-defined than serologically-defined antigenic determinants. Both cellular and Numeral immune responses to ACh receptors can be induced experimentally. Sufficient antigenic homology exists between receptors of different species that electric organ receptors are capable of inducing in mammals experimental autoimmune myasthenia gravis. Syn-geneic muscle receptor also is immunogenic in rats. Induction of both myasthenia and antibodies to ACh receptor requires participation of thymus-derived lymphocytes. The majority of ACh receptors in myasthenic rat muscle exist complexed with antibody, but antibody is not bound directly to the receptor's ACh-binding site. Anti-receptor antibodies in vitro are capable of impairing the electrophysiological function of ACh receptors with minimal blocking of the ACh-binding site and in the absence of complement. Thus, myasthenia gravis and its experimental model provide unique biological tools for studying the structure, function and pathology of cell membrane receptors.
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