DEVELOPMENTAL ADAPTATIONS OF TRYPANOSOMA CRUZI TO THE VERTEBRATE IMMUNE SYSTEM

在这个项目中，我们一直在研究 克氏锥虫对脊椎动物宿主的危害，特别是表面 表鞭毛体(载体)形态发生过程中的膜变化 阶段)到准环类鞭毛虫(脊椎动物阶段)。在报告期间 期间，我们继续研究元环的机制 锥虫对裂解产生抵抗力是通过替代途径 补体(ACP)。对纯化补体成分的研究揭示了 与上鞭毛虫相比，亚环类鞭毛虫结合 最低限度的B因子，这是机场核心计划中的一个重要辅助因素。在……里面 与其他系统获得的研究结果相比， 调节成分H在激活表鞭毛体和 非激活的亚环类鞭毛虫。酶治疗研究 提示亚环类鞭毛虫不能激活 ACP是由于它们对链霉素酶和衣霉素敏感的阐述。 分子。 在相关研究中，我们研究了一个72,000个MN的表达 糖蛋白(GP72)(先前我们证明是C3的受体 在昆虫和培养产生的准环类鞭毛虫上)。 用单抗检测到昆虫表面的GP72 后循环，但在培养产生的有机体上没有发现。因为由 表面标记和免疫沉淀，我们能够检测到 分子在这个舞台上，它显然是被修饰的，表达较少 抗体可与完整寄生虫结合的表位比其 等效于附生孢子。 最后，用兔抗独特型抗体针对一种 抗GP72的单抗，我们能够引起抗体反应 抗小鼠、兔和小鼠GP72分子上的碳水化合物决定因素 豚鼠。

In this project, we have been studying developmental adaptations of Trypanosoma cruzi to the vertebrate host, and in particular, surface membrane changes occuring during the morphogenesis of epimastigotes (vector stage) to metacyclic trypomastigotes (vertebrate stage). During the report period, we continued to investigate the mechanism by which metacyclic trypomastigotes become resistant to lysis by the alternative pathway of complement (ACP). Studies with purified complement components revealed that in comparison to epimastigotes, metacyclic trypomastigotes bind minimal amounts of Factor B, an essential co-factor in the ACP. In contrast, to the findings obtained with other systems, binding of the regulatory component H was equivalent in activating epimastigotes and non-activating metacyclic trypomastigotes. Enzyme treatment studies suggested that the incapacity of metacyclic trypomastigotes to activate the ACP was due to their elaboration of pronase and tunicamycin sensitive molecules. In related studies, we investigated the expression of a 72,000 MN glycoprotein (GP72) (previously shown by us to be the acceptor for C3 on epimastigotes) on insect and culture derived metacyclic trypomastigotes. Using monoclonal antibodies, GP72 was detected on the surface of insect metacyclics but was not found on culture generated organisms. Since by surface labelling and immunoprecipitation we were able to detect the molecule on this stage, it apparently is modified and expresses fewer epitopes accessible to antibody binding on intact parasites than its equivalent on epimastigotes. Finally, using rabbit anti-idiotypic antibodies directed against an anti-GP72 monoclonal antibody, we were able to raise an antibody response against carbohydrate determinants on the GP72 molecule in mice, rabbits and guinea pigs.