IMMUNOREGULATION /IMMUNE RECOGNITION IN FILARIAL/NONFILARIAL PARASITIC INFECTIONN

这个项目的压倒一切的目标是提供一种机械的 了解对丝虫寄生虫的免疫应答 控制住了。这个项目的三个主要方面涉及 淋巴丝虫病和丝虫病患者寄生虫特异性免疫反应的研究 盘尾丝虫病的调节、保护性免疫和 这些宿主反应的遗传基础。 寄生虫特异性的无能，一种特定的细胞对 丝虫抗原(对非寄生虫抗原和有丝分裂原有反应 保持完好无损)，是免疫反应的标志 淋巴微丝核型的无症状个体 丝虫病，最常见的临床表现是 感染丝虫的人。此前，我们已经确定这一点 低反应状态与以下频率降低相关 抗原反应性T和B细胞，这种低反应性 通过抗原反应细胞主动下调来调节 产生IL-10和转化生长因子-β。因此，第一部分的目标是 该项目是为了确定这一点所依据的机制 抗原特异性的免疫反应调节正在发挥作用。 之前在危地马拉库克群岛和 厄瓜多尔已经确认了一群人，尽管他们终生 居住在丝虫病高流行地区，保持无感染。 这些所谓的假定免疫的个体很可能提供了 这些感染中的保护性免疫，并提供了 研究它们的免疫反应和诱导它们的抗原。 为什么不同的个体产生不同的免疫反应 丝虫感染(和不同的临床结果 结果)是一个尚未解决的重要问题。 我们正在探索遗传因素或其他因素可能发挥的作用 对寄生虫的不同反应机制 同时研究了母体抗原与母体的关系 感染以及随后的临床和免疫学结果。

The overriding goal of this project is to provide a mechanistic understanding of how the immunologic responses to filarial parasites are controlled. The three major aspects of this project involved the parasite-specific immune responses in lymphatic filariasis and onchocerciasis in terms of regulation, protective immunity and the genetic underpinnings of these host responses. Parasite-specific anergy, a specific cellular unresponsiveness to filarial antigens (with responses to nonparasite antigens and mitogens remaining intact), is the hallmark of the immune response seen in asymptomatic individuals with the microfilaremic form of lymphatic filariasis, the clinical manifestation most commonly found in filarial-infected individuals. Previously, we had established that this hyporesponsive state was associated with a decreased frequency of antigen-reactive T and B cells and that this hyporesponsiveness was mediated through active downregulation by antigen-reactive cells that produced IL-10 and TGF-beta. Thus, the objective of the first part of the project was to identify the mechanisms by which this antigen-specific modulation of immune responsiveness was working. Previous studies carried out in both the Cook Islands, Guatemala, and Ecuador have identified groups of individuals who, despite lifelong residence in filarial-hyperendemic regions, remain infection free. These so-called putatively immune individuals likely provide the key to protective immunity in these infections and provide the rationale for studying both their immune responses and the antigens that induce them. Why different individuals develop different immunologic responses to filarial infection (and have different clinical outcomes as a consequence) is an important question that still has not been resolved. We are exploring the possible role of genetic factors or other mechanisms underlying the differential responsiveness to parasite antigen seen and at the same studying the relationship between maternal infection and subsequent clinical and immunological outcome.