MECHANISMS WHEREBY CD4 T CELLS ACTIVATE AMI AND CMI

尽管多年来为征服疟疾作出了大量努力，但它仍然是一个 传染病导致的主要死亡原因最近出现的 抗药性疟疾寄生虫和杀虫剂的发展 由蚊媒共同产生抗药性， 基于免疫的治疗或预防非常理想。为此，需要 对疟疾抗原免疫反应的详细了解。 CD 4 + T细胞被认为是必不可少的决议， 血液阶段疟疾（在这个建议中检查的阶段），但很少 关于CD 4 + T细胞如何影响保护性效应子的研究 机制等解决不同啮齿动物引起的急性感染 不同种类的疟原虫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， P.查鲍迪通过细胞介导的免疫。我们的目标是利用这些物种 阐明CD 4 + T细胞在疟原虫中的分子机制， 细胞通过分化成不同的Th细胞表型来调节B 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细胞分化及其 解决感染的要求。这些发现将是 随后的研究旨在确定Th细胞- 分化影响保护性抗体的选定参数 发育和巨噬细胞的功能。我们也要谈谈 抗体是否增强体内巨噬细胞功能问题 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.