IMMUNOREGULATION /IMMUNE RECOGNITION IN FILARIAL/NONFILARIAL PARASITIC INFECTIONN

这个项目的首要目标是提供一个机械的 了解对丝虫寄生虫的免疫反应是如何 控制。该项目的三个主要方面涉及 淋巴丝虫病的寄生虫特异性免疫应答， 在调节、保护性免疫和 这些宿主反应的遗传基础。 寄生虫特异性无反应性，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 保持完整），是免疫反应的标志， 无症状个体与微丝蚴血症形式的淋巴 丝虫病的临床表现最常见于 感染丝虫病的人。 此前，我们已经确定， 低反应状态与以下频率降低相关： 抗原反应性T和B细胞，这种低反应性是 通过抗原反应性细胞的主动下调介导， 产生IL-10和TGF-β。 因此，第一部分的目的是 该项目是为了确定这一机制， 免疫应答的抗原特异性调节正在起作用。 此前在库克群岛、危地马拉和 厄瓜多尔已经确定了一些个人群体， 居住在丝虫病高流行地区的人，保持无感染状态。 这些所谓的脓毒症免疫个体可能提供了 这些感染的保护性免疫，并提供理由， 研究它们的免疫反应和诱导它们的抗原。 为什么不同的人会产生不同的免疫反应 丝虫感染（并具有不同的临床结果， 这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的可能作用。 对寄生虫不同反应性的潜在机制 同时研究了母源性和非母源性之间的关系 感染和随后临床和免疫学结果。

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.