ANTIGEN PRESENTATION IN MALARIA INFECTION

人类感染疟原虫会导致长期、慢性 疾病，在此期间免疫力发展缓慢。 在啮齿类动物中，疟疾 要么走上致命的道路，要么在一到两个月内消退 以及随后对再次感染的抵抗力。 然而其中一个特点是 自然发生的疾病和实验疾病共有的疟疾 对寄生虫产生免疫反应的能力下降， 活动性感染期间的其他抗原。 研究结果 在啮齿类动物和人类中跨越数十年的研究表明 巨噬细胞功能缺陷是造成观察到的现象的原因 免疫抑制，以及寄生虫的代谢物，例如疟原虫色素 对这一现象起着直接作用。虽然巨噬细胞来自 已知受感染的小鼠会在体外和体内抑制抗体反应 在体内，它们作为 T 细胞反应的抗原呈递细胞的作用 没有被调查。此外，目前尚不清楚其他角色的作用 抗原呈递细胞，特别是 B 细胞和树突状细胞，发挥着 感染期间。 拟议工作的目的是评估 巨噬细胞、B 细胞和树突状细胞作为抗原的能力 使用约氏疟原虫小鼠模型呈递疟疾抗原细胞， 并确定彼此相互作用的 T 细胞的命运。 因为 由于它们吸收抗原的能力不同，很可能 这些子集不仅会呈现不同的疟疾肽阵列 用于T细胞识别，但吞噬抗原的功能 呈递细胞如巨噬细胞和未成熟的树突状细胞可能 因摄入寄生虫及其有毒产物而发生显着改变， 而 B 细胞则可以避免这种相互作用，因为它们不 吞噬细胞。 彻底了解什么类型的免疫反应 由 APC 亚群激发，它们呈现什么样的抗原，可能 帮助设计针对特定 APC 的疫苗。 这是 在规划流行病疫苗策略时尤其重要 疫苗可能已经感染疟疾的地区 这可能会改变他们的免疫系统处理抗原的方式。

Infection of humans with Plasmodia species results in prolonged, chronic disease, during which immunity is slow to develop. In rodents, malaria either follows a lethal course, or resolves within one to two months with subsequent resistance to re-infection. However one feature of malaria which is shared by naturally occurring and experimental disease is a decreased ability to generate immune responses to the parasite and other antigens during periods of active infection. Results from studies in both rodents and people spanning several decades have suggested that defective macrophage function is responsible for the observed immunosuppression, and that metabolites of the parasite such as hemozoin play a direct role in this phenomenon. Although macrophages from infected mice are known to inhibit antibody responses in vitro and in vivo, their role as antigen presenting cells for T cell responses has not been investigated. Furthermore, it is not clear what role other antigen presenting cells, specifically B cells and dendritic cells, play during infection. The aim of the work proposed is to evaluate the ability of macrophages, B cells and dendritic cells to act as antigens presenting cells for malaria antigen using a murine model of P. yoelii, and to determine the fate of T cells which interact with each. Because of their differential abilities to take up antigen, it is likely that these subsets will not only present different arrays of malaria peptides for T cell recognition, but the function of phagocytic antigen presenting cells such as macrophages and immature dendritic cells may be dramatically altered by ingestion of parasite and its toxic products, whereas B cells would be spared this interaction because they are not phagocytic. A thorough understanding of what type of immune responses are provoked by APC subsets, and what kind of antigen they present, may aid in the design vaccines targeted to particular APC. This is particularly important when planning vaccine strategies for endemic areas, where vaccines are likely to already harbor a malaria infection which could alter the way their immune system handles antigen.