Immunobiology of Rapid Expulsion

This application will continue the analysis of a recently discovered protective interaction between intestinal epithelial cells and parasite specific intestinal IgE (iIgE). The investigator has demonstrated <OL><LI>adoptive transfer of protection with serum IgE (sIgE); <LI> selective transport pathway of IgE that is restricted to the gut.</ol>
<P> Current preliminary data suggests that immune iIgE can interact directly with IL 4 stimulated intestinal epithelial cell lines to prevent adult T. spiralis invasion. In addition, the P.I. has evidence that the IgE mediated protection of epithelial cells is mast cell independent. These findings indicate that there are novel mechanisms of protection against nematodes and a role for IgE in intestinal immune responsiveness. The investigator believes that these observations place IgE at the center of the protective response to some nematodes and indicate that this apparently protective function free molecules is important in host defense. The P.I. proposes an analysis of the role of IgE in producing protection based on his in vivo and in vitro systems. Procedures are outlined that are intended to define and quantitate ex vivo and in vivo transport processes that traffic IgE from the plasma to the lamina propria and from the lamina propria to the lumen using a variety of techniques, including two photon emission imaging. <P>Furthermore, the investigator describes in vitro procedures that are intended to confirm this in a highly defined system. Plans include<ol><LI> to determine where IgE goes in the epithelial cell and whether it is surface or endocytosed IgE that is protective. <li> proposes in vivo experiments which will require the development of IgE mAbs and will demonstrate the significance of IgE in vivo. </ol><P>
The role of mast cells remains a question; the investigator has introduced (c kit deficient) Ws rats into his colony enabling him to address the role of IgE in ways that have not been accessible, and thus hopes to define the protective role of IgE.