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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI016618-04A1
Application #
3126735
Study Section
(SSS)
Project Start
1981-04-01
Project End
1988-02-28
Budget Start
1984-12-01
Budget End
1986-02-28
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of South Florida
Department
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612
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Smith, M S; Yamamoto, Y; Newton, C et al. (1997) Psychoactive cannabinoids increase mortality and alter acute phase cytokine responses in mice sublethally infected with Legionella pneumophila. Proc Soc Exp Biol Med 214:69-75
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Yamamoto, Y; Klein, T W; Friedman, H (1996) Immunoregulatory role of nitric oxide in Legionella pneumophila-infected macrophages. Cell Immunol 171:231-9
Retzlaff, C; Yamamoto, Y; Okubo, S et al. (1996) Legionella pneumophila heat-shock protein-induced increase of interleukin-1 beta mRNA involves protein kinase C signalling in macrophages. Immunology 89:281-8
Gebran, S J; Yamamoto, Y; Newton, C et al. (1995) LPS inhibits the intracellular growth of Legionella pneumophila in thioglycolate elicited murine peritoneal macrophages by iron-dependent, tryptophan-independent, oxygen-independent, and arginine-independent mechanisms. J Leukoc Biol 57:80-7
Yamamoto, Y; Retzlaff, C; He, P et al. (1995) Quantitative reverse transcription-PCR analysis of Legionella pneumophila-induced cytokine mRNA in different macrophage populations by high-performance liquid chromatography. Clin Diagn Lab Immunol 2:18-24

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