This application concerns the nature and mechanism of cell mediated immunity (CMI) to Legionella pneumophila, the etiologic agent of Legionnaire's disease. We wish to further characterize CMI in comparison to other aspects of immunity, such as humoral immunity, to L. pneumophila. A model system has been developed in guinea pigs to study this important opportunistic pathogen which produces pneumonia and other systemic infections in humans. Cutaneous hypersensitivity has been elicited in guinea pigs approximately 4 weeks after immunization with 109 whole Legionella organisms in complete Freund's adjuvant as well as following infection with sublethal numbers of the bacteria. Several in vitro correlates of CMI have been measured to assess this parameter. The strongest lymphocyte blastogenic reactions occurred with guinea pigs sensitized with Legionella in complete Freund's adjuvant. Intact bacteria and a soluble sonicate, as well as a purified cell wall antigen and lipopolysaccharide, were capable of inhibiting migration of macrophages from sensitized guinea pigs. These studies interrelate with ongoing investigations concerning ecology, epidemiology, and pathophysiology of Legionnaire's organism. Although much is now known about these organisms and especially epidemiology of infection, little is really known about factors influencing resistance or protection of individuals from infection. The purpose of this study is to continue investigation in a detailed manner in the guinea pig model using both high and low virulent L. pneumophila and determine the nature and mechanism of lymphoid cells responding to this organism. Purified populations of lymphoid cells, including T and B cells as well as macrophages, will be studied in order to determine the cell type involved in in vitro parameters of cellular immunity but also in protective immunity. The role of other intermediary factors, especially interleukins and interferons, are also being studied. In particular, the nature of macrophage (cellular) responses to L. pneumophila antigens, including whole cell vaccine, subcellular fractions and antigen-rich derivatives, are being examined in detail.
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