The overall goal of the program project is to characterize intestinal mucosal immune reactions that are important in the host interaction with environmental antigens. Within this central theme, the program is broadly based on multidisciplinary. The program brings together experienced investigators with expertise in immunology, microbiology, cell biology, molecular biology, and biochemistry from several divisions and three departments to accomplish the program's major objectives. Research Unit 1 will define mechanisms by which mucosal T cells and T cell products can regulate IgA responses. This unit will also continue studies to define mechanisms by which B cells are activated by bacterial polysaccharide antigens. These studies are key to understanding normal humoral immune function within the intestinal tract and how such immune responses can be rationally manipulated. Reseach Unit 1 also explores the genetic basis of an intestinal disease (Celiac disease) and a skin disease (Dermatitis Herpetiformis). Both diseases are activated by exposure to common dietary proteins (i.e., wheat gliadins and similar proteins in orther grains). Research Unit 2 focuses on immune and nonimmune mechanisms involved in the host interaction with a protozoan parasite Giardia lamblia. These studies will increase understanding of how the mucosal immune system interacts with an intestinal parasite, and provide strategies for the development of a vaccine agains giardiasis. Research Unit 3 will define critical genes and mechanisms involved in pathogenicity and immune resistance to an intestinal bacteria. Research Unit 4 will characterize rodent and human mucosal mast cells, and the effects of their products on intestinal epithelial cell growth and function. Research Unit 5 examines the role of complement components in host resistance to two intestinal protozoan parasites, Giardia lamblia and E. histolytica. Research Unit 6 focuses on the role of macrophage products in intestinal inflammatory reactions by studying the regulation of eicosanoid synthesis and secretion, and ways by which eicosanoid production can be specifically inhibited. The six research units and 7 projects are supported by 4 shared core facilities devoted to tissue culture, molecular biology, murine breeding and administration. This broad based program hold great promise for providing new insights into mechanisms important in intestinal disease and should point towards new strategies for disease prevention and treatment.
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