The overall aim of the proposed interdisciplinary research unit will be to study the immunological behavior of the intestinal mucosal immune system. The research unit will encompass seven projects directed toward understanding the cellular and humoral immune responses of the intestine, with each project examining a different intestinal immunity aspect. Four of the seven projects will study respectively antigen processing by M cells in the epithelium over Peyer's patches, intestinal IgA response to specific antigens, the development of intestinal IgA production and of IgA transport by the intestine and liver, and the effect of aging on the intestinal immune response. Other projects will examine the immune response of the intestine to a model protozoan parasite (Giardia muris), the role of cellular immunity in defense against colonic carcinoma in experimental animals, and the imunogenetic factors in human inflammatory bowel disease. Facilities for microscopy and for the production and purification of monoclonal antibodies are an integral component of the overall program. Two core facilities will be established. The first will provide facilities for culturing hybridoma cells, producing monoclonal antibodies, purifying these antibodies and conjugating them with fluorochromes and biotin. In addition, this core facility will generate new hybridoma cell lines producing additional monoclonal antibodies required by the investigators in the program project. The second core facility will provide light microscopy, fluorescence and phase contrast microscopy, electron microscopy, video recording of living cells, and photomicrography. Through structured collaboration, mutual discussion and shared resources, these distinct, but closely interrelated studies are intended to achieve an understanding of the overall immune response of the intestine, including the regulation of this response.
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