Cell-mediated immunity and antibody responses in the respiratory tract after local and systemic immunization

Abstract

The cell-mediated immune response on the secretory surface of the lower respiratory tract was investigated and compared to the systemic cell-mediated immune response and to the secretory and systemic antibody responses. Guinea pigs were immunized either parenterally or locally with dinitrophenylated human IgG. The effect of rendering animals tolerant on the local cell-mediated response and on the local antibody response was also studied. The antibody response in the bronchial washing fluids was predominantly of the IgA class. In the animals rendered tolerant by administering large doses of the antigen intravenously, the secretory antibody response was significantly reduced to about 40% of the levels in the animals which were not tolerant. Cellular immunity was assayed using the inhibition of macrophage migration. In animals which were immunized subcutaneously, splenic lymphocytes strongly inhibited the migration of normal guinea pig macrophages; however cells obtained from bronchial washings from the same animals exhibited little or no inhibition of macrophage migration in the presence of antigen. In the animals which were immunized by nose drops, splenic lymphocytes showed virtually no inhibition of macrophage migration; however, bronchial washing lymphocytes strongly inhibited the migration of normal macrophages. Thus, nose drop immunization gave rise to a significantly greater local cellular immune response than did parenteral immunization. In those animals which were immunized by nose drops after a tolerizing dose of antigen, there was virtually no inhibition of macrophage migration by either the cells from the spleens or bronchial washings. Studies were done which demonstrated that a substance similar to macrophage-inhibition factor was liberated by the bronchial washing cells on incubation with the antigen. Studies were also done which indicated that secretory antibody played no role in the inhibition of macrophage migration when bronchial washing lymphocytes were used. Lymphocytes were purified from bronchial washings and were found to inhibit normal macrophage migration in the presence of antigen to the same extent that the mixed population of lymphocytes and pulmonary macrophages did. Thus this study supports the concept that local cellular immunity can be initiated independently of systemic cellular immunity.