Proposed research focuses on the interface between infective L1 larvae of Trichinella spiralis and the host at the level of the small intestinal epithelium, the parasite's habitat. The objective is to test the hypothesis that physiological changes in epithelium, mediated through an immunological reaction, are important in effecting the rapid rejection of L1 larvae in rats and guinea pigs undergoing a challenge infection.
Specific aims are to (a) characterize small intestinal epithelial physiology in nonimmunized and immunized rats and guinea pigs, (b) provide evidence that an attempt by the L1 stage to penetrate tissue is necessary to elicit epithelial responses in immunized hosts, (c) provide evidence that epithelial changes elicited in immunized hosts are mediated by an anaphylactic reaction, and (d) determine the physiological characteristics of epithelium in immunized, challenged hosts that are linked temporally and spatially with the capacity to express rapid rejection.
Aims will be pursued using several procedures to assess epithelial functions in alternative hosts models. Experimental designs will include as hosts (a) uninfected rats and guinea pigs and their counterparts primed by infection to express rapid rejection, (b) rats and guinea pigs primed for expression of rapid rejection by inoculation with worm antigens, (c) passively immunized rats and guinea pigs, (d) rats treated with steroids to suppress rapid rejection, (e) athymic rats, and (f) rats infected with parasites other than T. spiralis. Alterations in epithelial function elicited by challenge with L1 larvae or their antigens used in neat form, incorporated into liposomes or adhered to a heterologous parasite, will be investigated. Electrophysiological and isotope tracer methodologies, cell fractionation procedures, lectin binding assays and enzymatic analyses will be used. Procedures will be employed to study intestinal tissue in full thickness, isolated epithelial cells and brush border and basolateral membranes of these cells. Host hypersensitivity will be gauged through passive cutaneous anaphylaxis and Schultz-Dale reactions and an in vivo """"""""equivalent"""""""" of the Schultz-Dale reaction which involves monitoring infection- induced myoelectric activity in conscious hosts. The objective is to define the physiological basis of acquired resistance to infective larvae of T. spiralis. Additionally, the project will lead to the development of models for the study of immunopathological and immunophysiological processes in mucosal tissues down to the subcellular level.
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