Our objective is to examine the pattern(s) of tissue injury resulting from the activation of the efferent limb of the intestinal (or systemic) immune response by antigen challenge administered via the lumen of the gut. Based on the results of experiments performed during the previous two years of grant support, it is planned to broaden these objectives to include the characterization of the fragments of administered antigen that appear in the systemic circulation after feeding and to determine some of their biologic functions. Further, it is planned to include under the concept of "injury", the broadening of anaphylactic sensitivity that may occur in animals as the result of enhanced uptake of bystander antigens from the intestine during the altered intestinal permeability which accompanies local intestinal anaphylaxis. Specifically, it is sought to: I. characterize the fragments of certain dietary antigens detected n the systemic circulation of adult rats and to test their role in the induction of systemic tolerance to ingested antigens. II. Determine whether the enhanced uptake of bystander antigens present in the intestine during local anaphylaxis contributes to the broadening of anaphylactic sensitivity to ingested antigens. III. Determine the site(s) and the consequence(s) of interaction of dietary antigen with IgG antibodies in rats prepared with or without IgE antibodies to the corresponding antigen. IV. Determine the histopathology of the local and remote tissue injury resulting from the ingestion of antigen in immunized rats.