ANTIGEN PRESENTATION IN MALARIA INFECTION

疟疾感染中的抗原呈递

• 批准号: 6328769
• 负责人: ANNE C AVERY
• 金额: $ 26.14万
• 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/6328769
• 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，在此期间免疫力发展缓慢。在啮齿类动物中，疟疾 要么走致命的路线，要么在一到两个月内痊愈 对再次感染有抵抗力。然而，它的一个特点是 自然发生和实验性疾病所共有的疟疾 是对寄生虫产生免疫反应的能力降低 活动性感染期间的其他抗原。研究结果 在啮齿动物和跨越几十年的人类中都表明 巨噬细胞功能缺陷是观察到的 免疫抑制，以及寄生虫的代谢物，如血球蛋白 在这一现象中起到了直接作用。虽然巨噬细胞来自 已知受感染的小鼠在体外和体内抑制抗体反应。 在体内，它们作为T细胞反应的抗原提呈细胞的作用 没有被调查过。此外，还不清楚其他角色是什么 抗原提呈细胞，特别是B细胞和树突状细胞，发挥作用 在感染期间。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 用约氏疟原虫的小鼠模型呈现疟疾抗原的细胞， 并确定与之相互作用的T细胞的命运。因为 在它们吸收抗原的不同能力中，很可能 这些子集将不仅呈现不同阵列的疟疾多肽 对于T细胞识别，但吞噬细胞抗原的功能 巨噬细胞和未成熟树突状细胞等呈递细胞可能 会因摄入寄生虫及其有毒产品而发生显著变化， 而B细胞将免于这种相互作用，因为它们不是 吞噬功能。彻底了解哪种类型的免疫反应 是由APC亚群激发的，以及它们呈现的是哪种抗原，可能 帮助设计针对特定APC的疫苗。这是 在规划地方性疾病的疫苗策略时尤为重要 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。