MECHANISMS WHEREBY CD4 T CELLS ACTIVATE AMI AND CMI

尽管多年来为征服疟疾做出了密集的努力，但它仍然是一个 主要死因是传染病。最近的到来 耐药疟疾寄生虫的研究和杀虫剂的开发 蚊媒的抗性共同使蚊子的发展 基于免疫的治疗或预防是非常可取的。要做到这一点，需要 对疟疾抗原免疫反应的详细了解。 CD4+T细胞被认为是解决疾病的关键 血液期疟疾(本提案中研究的阶段)，但几乎没有 已知CD4+T细胞如何实际影响保护性效应器 机械装置。不同啮齿动物引起的急性感染的解决 疟原虫的物种似乎使用不同的分解机制， 约氏疟原虫被抗体介导的免疫(AMI)抑制和 通过细胞免疫产生的沙包氏杆菌。我们的目标是利用这些物种 以阐明CD4+T细胞感染的分子机制 细胞通过分化成不同的Th细胞表型，调节B细胞 疟疾期间细胞和巨噬细胞的功能。为了实现这一目标，我们 打算首先详细研究Th细胞的分化和其 感染消退的要求。这些发现将是 纳入后续研究，旨在确定Th细胞是如何- 差异性对保护性抗体选择参数的影响 疟疾期间的发育和巨噬细胞功能。我们还将解决 抗体在体内是否增强巨噬细胞功能的问题 清除血液中的寄生虫。这些研究的结果将有助于 未来实验的设计对我们理解 负责解决疟疾的保护性免疫机制 在人类身上。

Despite many years of intensive effort to conquer malaria, it remains a leading cause of death due to an infectious disease. The recent advent of drug-resistant malarial parasites and the development of insecticide resistance by the mosquito vector jointly make the development of immune-based therapy or prophylaxis highly desirable. To do so, requires a detailed understanding of the immune response to malarial antigens. CD4+ T cells are believed to be essential for the resolution of bloodstage malaria (the stage examined in this proposal), but little is known about how CD4+ T cells actually influence protective effector mechanisms. Resolution of acute infections caused by different rodent species of Plasmodium appear to use distinct mechanisms of resolution, with P. yoelii being suppressed by antibody-mediated immunity (AMI) and P. chabaudi by cell-mediated immunity. Our goal is to use these species of Plasmodium to elucidate the molecular mechanisms whereby CD4+ T cells, by differentiating into distinct Th cell-phenotypes, regulate B cell and macrophage function during malaria. To address this goal, we intend to first examine in detail Th cell-differentiation and its requirement for resolution of infection. These findings will be incorporated into subsequent studies aimed at identifying how Th cell- differentiation affects selected parameters of protective antibody development and macrophage function during malaria. We will also address the question of whether antibodies augment macrophage function in vivo to clear parasites from blood. The results of these studies will aid in the design of future experiments crucial to our understanding of protective immune mechanisms responsible for the resolution of malaria in humans.