Disease syndromes associated with lymphatic dwelling filariae in man appear to be altered by the host immune response and both hyper and hyporesponsive immunologic conditions exist. However, little direct evidence is available which links these immune responses with lymphatic inflammation. The long term goal of the proposed study is to characterize the pathogenesis of lymphatic inflammatory responses induced by filarial nematodes using Brugia pahangi infected Mongolian jirds (Meriones unguiculatus) as a laboratory model.
The specific aims proposed are 1.) to identify and characterize the cells and humoral factors involved in the induction and/or modulation of the granulomatous inflammatory response to B. pahangi antigens, by using adoptive transfer and in vitro culture methods. 2.) To characterize the production of the cytokines, interlukin-1, interlukin-2, migrations inhibitory factor, and fibroblast stimulation factor, from filariae stimulated lymphocytes and macrophages recovered from jirds with reactive and modulated infections. 3.) To determine the effect of stage specific parasite sensitizations, on granulomatous lymphatic lesions and concomitant immune responses induced by subsequent L3 infections using surgical and inoculation methods to expose hosts to a limited number of filarial life cycle stages prior to challenge infection. 4.) To identify specific B. pahangi protein antigens associated with the granulomatous inflammatory response during reactive and modulated periods of the infection, using contemporary methods of protein frationation, coupled with quantitative in vivo measurements of granulomatous inflammation and qualitative in vitro measurements of antibody by Western immunoblot methods. Obtaining the goals of this study would advance the understanding of the pathogenesis of lymphatic filariasis, and thus, increase in the future, the feasibility of control and amelioration of the tissue damaging lesions produced by these parasites.
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