This Program Project is aimed at a study of various aspects of local immunologic function and dysfunction within the gastrointestinal tract with special emphasis on defining immunologic and non-immunologic factors contributing to the mucosal barier to antigens, bacteria and toxins. Major areas of investigation will include the following: 1) A detailed study of macromolecular transport in the intestine including defining mechanisms of host defenses against excessive antigen uptake, determining factors contributing to increased antigen penetration and defining the disease consequences (pathophysiologic mechanisms) resulting from increased penetration of intestinal antigens. 2) In an extension of previous studies of immunologic mechanisms of allergic gastroenteropathy, animals models will be used to define the role of bystander antigen uptake across an inflammed intestine or during intestinal anaphylaxis and the consequences of immune complexes formation on propagation of intestinal and systemic disease states. 3) An extensive study of gut processing of orally ingested antigens will be undertaken. This study will attempt to define factors contributing to immune tolerance and to local immunologic reactions. 4) The role of antigen/endotoxin uptake in newborns and its contribution to neonatal liver disease will be studied with special emphasis on the contribution of Kupffer cell phagocytosis in hepatic clearance of portal blood antigens. 5) Finally, the intestinal macrophage will be isolated and characterized with respect to its role in antigen processing and its contribution to """"""""T"""""""" cell proliferation vis-a-vis release of chemotactic factors. These results will be compared to macrophage function in the developing animal and in various intestinal disease states.
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