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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL019873-11
Application #
3335985
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1979-06-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Richerson, H B; Adams, P A; Iwai, Y et al. (1990) Uptake of muramyl dipeptide fluorescent congeners by normal rabbit bronchoalveolar lavage cells: a study using flow cytometry. Am J Respir Cell Mol Biol 2:171-81
Upadrashta, B S; Adams, P A; Kopp, W C et al. (1989) Bronchoalveolar lavage T-cell and Ia antigen quantitation by flow cytometry in acute and chronic experimental hypersensitivity pneumonitis. Exp Lung Res 15:359-73
Peterman, J H; Butler, J E (1989) Application of theoretical considerations to the analysis of ELISA data. Biotechniques 7:608-15
Upadrashta, B; Croom, J; Kopp, W C et al. (1988) T cell localization in rabbit models of acute and chronic experimental hypersensitivity pneumonitis. J Allergy Clin Immunol 81:821-8
Kopp, W C; Suelzer, M T; Richerson, H B (1988) Alveolar macrophage immunosuppression is maintained in rabbit models of hypersensitivity pneumonitis. J Allergy Clin Immunol 82:204-12
Hiebert, C K; Kopp, W C; Richerson, H B et al. (1988) Synthesis of fluorescent muramyl dipeptide congeners. 2. J Med Chem 31:2022-4
Kopp, W C; Dierks, S E; Butler, J E et al. (1985) Cyclosporine immunomodulation in a rabbit model of chronic hypersensitivity pneumonitis. Am Rev Respir Dis 132:1027-33