IMMUNITY TO PARASITIC INFECTION

描述(改编自调查人员摘要)：尽管 线虫免疫应答调控的研究进展 感染和对生理性和炎症性的广泛描述 寄生个体肠道的变化，目前的理解 抗线虫免疫机制的研究还很有限。一个原因是 这一缺陷是未能整合对 了解免疫反应的寄生虫生物学。这样一个完整的 方法，如本提案所述，将产生新的知识， 将促进肠道治疗和疫苗的开发 病原体。我们的长期目标是阐明 宿主的免疫反应干扰线虫的寄生，导致 获得许可和豁免权。旋毛虫在一种 易感宿主入侵后通过肠道传播 上皮细胞。私家侦探假设入侵和入侵的过程 排出的糖蛋白促进了细胞间的转运。 被感染的幼虫。这些糖蛋白含有复杂的多聚糖， 上面覆盖着一种名为tyvelose的新型糖。调查员已经证明 能够结合Tyvelose的抗体保护上皮细胞免受入侵和 使已建立的旋毛虫幼虫放弃它们的生态位。在这 提案，目的是为了研究建立的分子基础 旋毛虫上皮生态位的表达，并阐明其作用机制。 保护性抗体的干扰。具体目标如下 以下问题：1)酪氨酸特异性免疫球蛋白抗体如何 干扰寄生虫进入上皮细胞或通过上皮细胞移动？ 2)旋毛虫糖蛋白如何与宿主细胞相互作用以促进 寄生？3)寄主细胞如何参与 线虫入侵？实验方法将在很大程度上依赖于一种新的 调查员在上一个供资期间开发的工具。她 首次表明培养的上皮细胞系 易受旋毛虫入侵的。这项化验使她能够研究 进程或入侵、建立生态位和在有条件的情况下驱逐 这是可以小心控制和容易操纵的。她计划 将此分析应用于跨学科。她计划将这种化验方法应用于 用跨学科的方法调查寄生虫和 对肠道线虫的免疫力。

DESCRIPTION (adapted from investigator's abstract): Despite considerable recent progress in research on regulation of immune responses to nematode infections and extensive descriptions of the physiologic and inflammatory changes in the intestine of parasitized individuals, current understanding of the mechanisms of anti-nematode immunity remains limited. One cause for this deficiency has been a failure to integrate an understanding of parasite biology with knowledge of the immune response. Such an integrated approach, as described in this proposal, will produce new knowledge that will facilitate development of treatments and vaccines against intestinal pathogens. Our long range goal is to elucidate the ways by which the host's immune response interferes will parasitism by nematodes, leading to clearance and immunity. Trichinella spiralis initiates infection in a susceptible host when it invades and then travels through intestinal epithelial cells. The P.I. hypothesizes that the processes of invasion and intercellular transit are facilitated by glycoproteins that are disgorged by infectious larvae. These glycoproteins bear complex glycans that are capped with a novel sugar, called tyvelose. The investigator has shown that antibodies able to bind tyvelose protect epithelia from invasion and cause established T. spiralis larvae to abandon their niche. In this proposal, the aim is to investigate the molecular basis for establishment of the epithelial niche of T. spiralis, and to elucidate the mechanism of interference by protective antibodies. The specific aims are formulated as the following questions: 1) How do tyvelose-specific IgG antibodies interfere with parasite entry into or movement through epithelial cells? 2) How do T. spiralis glycoproteins interact with host cells to facilitate parasitism? 3) How does the host cell participate in the process of nematode invasion? The experimental approach will rely heavily on a new tool that investigator developed during the previous funding period. She has shown for the first time that cultured epithelial cell lines are susceptible to invasion by T. spiralis. This assay allows her to study the processes or invasion, niche establishment and expulsion under conditions that can be carefully controlled and readily manipulated. She plans to apply this assay in an interdisciplinary. She plans to apply this assay in an interdisciplinary approach in the investigation of parasitism and immunity against intestinal nematodes.