UNDERLYING MECHANISMS OF SCHISTOSOME/SNAIL COMPATIBILITY

由于人口的巨大负担， 曼氏血吸虫病流行区血吸虫病的调查 负责传播这些人类寄生虫的基本机制， 它们的中间软体动物宿主是理想的。 这项研究旨在 了解毛蚴幼虫如何能够穿透蜗牛 转化成孢子囊而不会引发攻击性防御 应答 由于个别蜗牛（光滑双脐螺）可能是 对单个S易感或抵抗。mansoni，细胞和 将寻找这种变异性的分子基础。 至少一些 这种软体动物的内部防御系统的组成部分， 调节由吸虫寄生虫和压力。 因此，继 治疗被证明调节血细胞活性，这种治疗的影响 改变的状态将在蜗牛抗性测定中进行评估。 测定 包括体外吞噬作用、细胞粘附和细胞介导 细胞毒性和体内对S. mansoni 一个假设， 蜗牛和蜗牛的兼容性部分是由于模仿 碳水化合物表位将使用多克隆血清进行测试， 进行蛋白水解降解，并使用已知的碳水化合物表位 作为竞争配体。 显著改善体外定量 细胞毒性将使我们能够确定耐药血浆是否 加速杀死孢子囊。 另一个假设是 将测试溶酶体衍生的血浆酶在调节抗性中的作用 在体内和体外使用来自适当处理的蜗牛的血浆 和确定的酶。 将寻求50 kD等离子体的功能作用 在对PR 1有抗性的蜗牛品系中唯一发现的组分 链球菌菌株mansoni 多克隆抗血清将用于阻断 效应子功能，并且亲和纯化的血浆组分将被 评价其促进识别和/或细胞毒性的能力 血细胞效应器功能。 最后，一部小说的相关性 α-巨球蛋白样蛋白在蜗牛血浆中的作用， 将对一些不愉快的遭遇进行调查。

On account of the considerable burden placed on human populations by Schistosoma mansoni in schistosome-endemic areas, an understanding of the basic mechanisms responsible for transmission of these human parasites via their intermediate molluscan hosts is desirable. This research seeks to understand how it is that a miracidium larva is able to penetrate a snail and transform into a sporocyst without eliciting aggressive defensive responses. Since individual snails (Biomphalaria glabrata) may be susceptible or resistant to individual S. mansoni, the cellular and molecular bases for this variability are to be sought. At least some components of this mollusc's internal defense system are subject to modulation by trematode parasites and by stress. Therefore, following treatments proven to modulate hemocyte activity, the influence of such altered states will be evaluated in assays of snail resistance. Assays include in vitro phagocytosis, cytoadherence and cell mediated cytotoxicity, and in vivo resistance to S. mansoni. An hypothesis that the compatibility of schistosome and snail is due in part to mimicry of carbohydrate epitopes will be tested using polyclonal sera, with antigens subjected to proteolytic degradation, and known carbohydrate epitopes used as competing ligands. Substantively improved quantification of in vitro cytotoxicity will allow us to determine whether resistant plasma accelerates sporocyst killing. Another hypothesis implicating lysosomally-derived, plasma enzymes in modulating resistance will be tested both in vivo and in vitro using plasma from appropriately treated snails and defined enzymes. A functional role will be sought for a 50 kD plasma component found uniquely in strains of snail which are resistant to the PR1 strain of S. mansoni. Polyclonal antisera will be used in efforts to block effector functions, and the affinity-purified plasma component will be evaluated for its ability to facilitate recognition and/or cytotoxic hemocyte effector functions. Finally, the relevance of a novel alpha-macroglobulin-like protein in snail plasma to outcomes of snail - schistosome encounters will be investigated.