The significance of schistosomiasis as a globe-spanning public health problem, and the significance of immunological approaches to its eventual control and elimination, are well known: The most fundamental aspect of dual immunity in schistosomiasis involves the existence of two largely distinct pathways of specific immune induction; leading to acquired (concomitant) immunity on the one hand and granulomatous hypersensitivity to tissue eggs of the parasite on the other. However, certain connections between these two pathways exist, and examination of several of these links constitutes the basis of this proposal. Using primarily nonhuman primates (baboons and tamarins), we propose to investigate the following: 1. the occurrence of egg-induced pathology-associated resistance, as seen in the murine-Schistosoma mansoni system, in nonhuman primate models for human schistosomiasis. The effect of liver size on egg and schistosomula shunting to the lungs (i.e. """"""""liver leakiness"""""""") will be determined by comparing large (baboons) and very small (tamarins) primates. 2. baboons will be vaccinated with irradiated, cryopreserved schistosomula in order to ascertain vaccine effects, including stimulation of acquired immunity and induction of granuloma size reduction. Protection-associated antibodies will be sought. Further evidence for immunoregulation (modulation) in the granuloma reduction phenomenon will also be sought. 3. using hamsters and tamarins, we will test our new hypothesis of granuloma-mediated egg passage. An arterial embolism model to study the phenomenon in hosts of different immunological states will be developed. 4. the possibility of immune-mediated fecundity reduction will continue to be studied in in vivo (vaccination model) and in vitro systems.
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