Comparison of systemic and local immune responses after multiple pulmonary antigen exposures.

Both systemic and local immune responses were evaluated in five male cynomolgus monkeys after a primary and multiple secondary challenges of the lung with sheep red blood cell (SRBC) antigen. Comparisons of peripheral blood and pulmonary antibody-forming cell (AFC) responses were made after primary and multiple secondary intrapulmonary challenges with SRBC. The primary immune response to SRBC was characterized by a low lung to blood AFC ratio. This ratio, however, increased successively with each challenge, resulting in a 15-fold increase after the third exposure of the lung to SRBC. These data suggest a decreasing contribution of systemic AFC to the lung response with each successive challenge. Histopathologic and autoradiographic evaluation was done to compare a newly immunized lobe, a multiply challenged lobe, and a saline instilled lobe. Large localized perivascular lymphoid follicles appeared in the lung lobe challenged multiple times. About 17% of these large mononuclear cells had taken up 3H-thymidine compared to 5% in the newly immunized lobe and 3.8% in the control lobe. The number of proliferating cells appeared to reflect the degree of immune responsiveness within each lung lobe. Together these data support a hypothesis that after the primary immune response is established, the secondary immune response is generated by local clonal expansion of antigen-specific lymphocytes within the lung.