Habitual smoking alters numerous immunological parameters at the lung level in man, probably resulting in altered in vivo pulmonary immune function. In these studies, human in vivo pulmonary immune function will be investigated in nonsmokers and smokers by measuring antigen-specific immune responses to primary immunization of the lower respiratory tract. Primary immunization will be accomplished by transbronchoscopic instillation of a large molecular weight neoantigen, keyhole limpet hemocyanin (KLH) into a single lung segment. Inflammatory and immune events following lung immunization will be monitored in venous blood and bronchoalveolar lavage obtained from immunized and saline-instilled control lung lobes. The objectives of these studies will be: 1. To define dose-response relationships for the generation of primary immune responses after lung immunization with KLH. 2. To compare the immunoglobulin class and subclass distributions of responses to subcutaneous and intrapulmonary immunization with KLH. 3. To evaluate inflammatory and specific humoral immune events at the lung level after lung immunization with KLH through the use of bronchoalveolar lavage. 4. To assess for potential lymphocyte immunoregulation at the lung level after lung immunization by using flow cytometry to phenotypically characterize lymphocyte subsets in immunized and control lung lobes after immunization; and by examining the ability of lung T-cells to produce the lymphokines gamma interferon and IL-4. 5. To assess for modulation of alveolar macrophage function during the evolution of a primary pulmonary immune response by evaluating expression of HLA-DR antigen; and antigen-specific and nonspecific phagocytosis. 6. To compare responses to lung immunization in nonsmokers, and in a group likely to have altered pulmonary immune function, smokers. The proposed studies will result in elucidation of immune responses generated by antigen entering the human lung, an area of great basic and clinical importance. Furthermore, the approach to studying pulmonary immune function developed in these studies will provide a powerful tool for investigating conditions, such as habitual smoking, in which deranged functional lung immunity is likely to exist.
| Weissman, D N; Bice, D E; Crowell, R E et al. (1994) Intrapulmonary antigen deposition in the human lung: local responses. Am J Respir Cell Mol Biol 11:607-14 |
