UNDERLYING MECHANISMS OF SCHISTOSOME/SNAIL COMPATIBILITY

考虑到世界卫生组织给人类带来的巨大负担 曼氏血吸虫在血吸虫流行区的认识 这些人体寄生虫传播的基本机制是通过 它们的中间软体动物宿主是可取的。这项研究旨在 了解毛虫幼虫是如何穿透蜗牛的 并在不引发攻击性防御的情况下转化为孢子囊 回应。由于个别蜗牛(Biomphalaria Grarata)可能是 对单个曼氏葡萄球菌敏感或抗药性，细胞和 这种可变性的分子基础是需要寻找的。至少有一些 这种软体动物的内部防御系统的组件会受到 受吸虫寄生虫和压力的调节。因此，以下是 已证实可调节血细胞活性的治疗方法，其影响 改变的状态将在蜗牛抗性试验中进行评估。化验 包括体外吞噬、细胞黏附和细胞介导 对曼氏葡萄球菌的细胞毒性和体内抗药性。一种假设，即 血吸虫和蜗牛的相容部分是由于模仿了 碳水化合物表位将使用带有抗原的多克隆血清进行测试。 受到蛋白质降解的影响，并使用已知的碳水化合物表位 作为相互竞争的配体。实质性地改进了体外定量 细胞毒性将使我们能够确定耐药血浆 加速孢子囊的杀灭。另一个牵涉到的假说 溶酶体衍生的、调节抗性的血浆酶将进行测试 在体内和体外使用适当处理的蜗牛的血浆 并定义了酶。将为50kD的等离子体寻求功能作用 在对PR1具有抵抗力的钉螺品系中唯一发现的成分 曼氏链霉菌株。将使用多克隆抗血清来阻止 效应器功能，亲和纯化的血浆成分将 评估其促进识别和/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 钉螺血浆中α-巨球蛋白样蛋白对钉螺结局的影响 将对血吸虫遭遇进行调查。

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.