Date of Award
2-1987
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Sciences
First Advisor
Peter Abramoff
Second Advisor
James W. Scheffel
Third Advisor
James B. Courtright
Fourth Advisor
Jordan N. Fink
Fifth Advisor
Nickolas J. Calvanico
Abstract
The purpose of this thesis was to gain information on the role of the spleen, as the major organ of systemic immunity, in regulation of an antibody response by the lung following challenge with soluble antigen. Antibody responses to complex protein antigens are a sum of responsiveness to the antigenic determinants of the protein molecule. Antigenic determinants are those amino acid residues of the protein that elicit the production of antibodies. Sperm whale myoglobin (Mb) has been reported to contain five major antigenic determinants, each comprised of six or seven amino acid residues located on the exposed surface of the native protein. Syntheitc peptides, corresponding in sequence to the antigenic determinants of Mb, have been synthesized and were made available for use in these studies. To determine specificity of the systemic antibody response, three strains of inbred mice were immunized parenterally with Mb. These studies demonstrated that the pattern of response to the five antigenic determinants differed in each strain. In order to determine systemic influences on the pulmonary antibody responses, a local PFC response must be initiated following immunization of the respiratory tract. To ascertain the nature of regulatory elements present in the spleen, adoptive transfer experiments were conducted using the spleen cells of i.t. immunized, aerosolized mice. The data demonstrated that i.t. immunization and aerosolization of A/He mice with Mb plus MDP resulted in the presence of splenic antigen-specific T suppressor cells. Suppressor cells function through the elaboration of soluble factors. To investigate the role of soluble products, spleen cells of A/He mice, immunized via the lung, were sonicated and the cell-free supernatants recovered. Results from these studies indicated that systemic regulatory mechanisms were operative following immunization of the lung. Additional studies are needed to determine the ultimate role and mode of action of the splenic regulatory cells in augmentation of down-regulation of the pulmonary antibody response. Nevertheless, these studies do demonstrate the presence of splenic immunoregulatory cells and factors produced as a result of pulmonary antigenic challenge, and indirectly indicate that these cells and/or factors regulate the pulmonary immune response to inhaled antigens.