The long-term objective is to apply information acquired from immunophysiological investigations of enteric parasitism to determine (a) how to control of regulate responsiveness of the mucosal immune system (MIS) to soluble antigens or infectious agents having a mucosal portal of entry, (b) how immunocyte-nerve interactions are involved in the transduction of antigenic signals, and (c) how MIS-regulated intestinal functions adapt to injury. Proposed studies will enhance our knowledge about the role of the MIS in regulating intestinal functions during homeostasis and disease. Anticipated results will be applicable in future efforts to augment or boost mucosal immunity, to reconstruct a deficient or suppressed MIS, and to modulate a hyper-reactive MIS. The objective will be fulfilled by accomplishing three specific aims.
Aim 1 is to determine if enterally delivered antigens in the presence of actively transported hexose boost mucosal immunity in the small intestine and whether the boosting effect is expressed in extraintestinal mucosae.
Aim 2 is to determine how neuronal behavior is altered in Aplysia californica after the """"""""immune"""""""" response mounted by this mollusc is directed against its well- mapped nervous system.
Aim 3 is to determine the capacity of an immunophysiological process, i.e. anaphylactically mediated C1- secretion, to adapt to the injurious effects of gamma radiation.
Aims 1 and 3 focus primarily on responses triggered by type I hypersensitivity reactions in rats whose MIS is sensitized to antigens of the parasite, Trichinella spiralis. Immunity, reflected by local anaphylaxis, will be quantified by measuring antigen-induced alterations in net transmural ion transport, antigen-induced fluid secretion and acquired resistance to T. spiralis. Ion transport will be monitored electrophysiologically in vitro. Fluid secretion and immunity to the parasite will be measured following infection of intact hosts using techniques that permit the parallel recovery of intestinal fluid and mucosally established worms. Gamma irradiation will be from a cobalt source. To accomplish Specific Aim 2, immunocyte-nerve interactions will be characterized histologically and electrophysiologically after the """"""""immune"""""""" response mounted by Aplysia is directed against a target nerve by surgically implanting a cotton string around that nerve. Collection, storage, and analysis of electrophysiological data will be aided through the Computational Core facilities. Morphological states of tissues, relative to function, will be assessed using light and electronmicroscopic data obtained through facilities of the Cytobiology Core.
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