ANTIGEN PRESENTATION IN MALARIA INFECTION

疟疾感染中的抗原呈递

• 批准号: 6124357
• 负责人: ANNE C AVERY
• 金额: $ 28.82万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6124357
• 关键词: B lymphocyte; Plasmodium; RNase protection assay; T lymphocyte; antigen antibody reaction; antigen presentation; cell cell interaction; cellular immunity; dendritic cells; enzyme linked immunosorbent assay; flow cytometry; immunocytochemistry; immunoregulation; interferon gamma; interleukin 12; interleukin 2; laboratory mouse; leukocyte activation /transformation; macrophage; major histocompatibility complex; malaria; polymerase chain reaction; tissue /cell culture; tumor necrosis factor alpha

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.

人类感染疟原虫导致长期、慢性 疾病，在此期间免疫力缓慢发展。 在啮齿类动物中， 要么是致命的，要么是在一到两个月内解决， 随后对再次感染具有抵抗力。 然而， 疟疾是自然发生的疾病和实验性疾病 是对寄生虫产生免疫反应的能力下降， 在活动性感染期间的其他抗原。 的研究结果 在啮齿动物和人类身上的研究表明， 缺陷的巨噬细胞功能负责观察到的 免疫抑制和寄生虫代谢物如疟原虫色素 在这一现象中起着直接的作用。虽然巨噬细胞从 已知感染的小鼠会抑制体外和体内的抗体反应 在体内，它们作为T细胞应答的抗原呈递细胞的作用已经 没有被调查。此外，尚不清楚其他作用是什么。 抗原呈递细胞，特别是B细胞和树突细胞， 在感染期间。 拟议工作的目的是评价 巨噬细胞、B细胞和树突状细胞作为抗原的能力 使用约氏疟原虫的鼠模型， 并确定与它们相互作用的T细胞的命运。 因为 由于它们摄取抗原的能力不同， 这些亚群不仅呈现不同的疟疾肽阵列， 但吞噬抗原的功能 呈递细胞如巨噬细胞和未成熟树突细胞可 通过摄入寄生虫及其有毒产物而发生显著改变， 而B细胞将免于这种相互作用，因为它们不是 吞噬细胞的 彻底了解什么类型的免疫反应 是由APC亚群引起的，以及它们所呈现的抗原类型，可能 帮助设计针对特定APC的疫苗。 这是 在规划地方性流行病的疫苗战略时， 疫苗可能已经存在疟疾感染的地区 这可能会改变他们的免疫系统处理抗原的方式。