This program of research proposes to examine immunological and viral-immunological factors and interactions which may be involved in the pathogenesis of multiple sclerosis (MS). The laboratory models that will be utilized include acute and chronic experimental allergic encephalomyelitis (EAE) in its usual state as well as under suppression with COP I, myelin basic protein and, possibly, galactocerebroside; organotypic cultures of central and peripheral mammalian nerve tissues both as test objects for the presence and action (demyelination) of cellular and circulating immunological factors and effector (macrophage, enzyme) systems and as models of the pathological response; and the myelinated axons of the rabbit eye as the respond to the injection of components of the immunological response as they may act alone or in concert with the rabbit's response. The laboratory procedures which will be used to examine cell and serum factors from animals and man, and the models' responses include electron microscopy, immunohistochemistry, and immunological studies of suppressor T-cells. The possible viral involvement in demyelinative disorders will be examined in a number of studies including mechanisms by which viruses may interact with autoimmune disease, suppressor cell activity particularly in response to measles virus in MS patients, and the mechanism (s) of measles-induced suppression. Experimental allergic neuritis (EAN) and the Guillain-Barre Syndrome (GBS) will also be examined in studies similar to those for EAE and MS. Finally, immunological manipulations of cultured tissues will be employed in analysis of the cellular-membrane interactions in myelinogenesis.
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