The specific aims of this proposal are: 1) to characterize the lung's immune system following exposure to inhaled antigen and to define the influence of inhaled antigen on subsequent systemic and local immunologic responses; both immunogenesis and tolerogenesis are of interest; 2) to determine how the presence of pulmonary inflammatory and suppressive immunologic responses involving one antigen modify IgM, IgG and IgA antibody responses to a new antigen; and 3) to evaluate the influence of large doses of oral antigen on subsequent responses to inhaled antigen. Long term objectives are to define humoral responses to inhaled antigen and to clarify interrelationships between local and systemic immunologic mechanisms. Established rabbit models of acute and chronic hypersensitivity pneumonitis, antigen-specific desensitization, cyclosporine immunosuppression and appropriate controls including groups fed antigen will be utilized in these studies. Serum and local secretions, including bronchoalveolar and intestinal washes and bile, will be quantitated for specific antibody levels using an enzyme-linked immunosorbent assay (ELISA). Antibodies will be measured also in in vitro cultures of selected tissues including pulmonary parenchymal and airways tissues, gut, spleen and mediastinal, mesenteric and popliteal lymph nodes. Finally, localization of antibody-forming cells will utilize fluorescence microscopy and/or avidin-biotin immunoperoxidase techniques. The characterization of immunologic responses to inhaled antigen is important for our understanding mechanisms of immunomodulation which lead either to immunity or hypersensitivity, defense or inflammation, with implications for prevention and treatment of infectious and allergic human lung diseases.
