CYTOTOXIC RESPONSE TO HISTOCOMPATIBILITY ANTIGENS

对组织相容性抗原的细胞毒性反应

• 批准号: 6681308
• 负责人: Michael J Bevan
• 金额: $ 16.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6681308
• 关键词: Listeria; MHC class I antigen; Mycobacterium tuberculosis; T cell receptor; antigen antibody reaction; antigen presentation; bacteria infection mechanism; bacterial antigens; bacterial cytopathogenic effect; bactericidal immunity; cytotoxic T lymphocyte; disease /disorder model; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; helper T lymphocyte; host organism interaction; immunologic memory; laboratory mouse; leukocyte activation /transformation; recombinant virus; transfection; tuberculosis; virulence; Listeria; MHC class I antigen; Mycobacterium tuberculosis; T cell receptor; antigen antibody reaction; antigen presentation; bacteria infection mechanism; bacterial antigens; bacterial cytopathogenic effect; bactericidal immunity; cytotoxic T lymphocyte; disease /disorder model; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; helper T lymphocyte; host organism interaction; immunologic memory; laboratory mouse; leukocyte activation /transformation; recombinant virus; transfection; tuberculosis; virulence

DESCRIPTION(provided by applicant): Our goal is to investigate the CD4 and CD8 T cell response to pathogenic infectious agents to uncover basic principles of T cell biology in controlling these infections. Two contrasting models of intracellular bacterial pathogens are chosen to ask fundamental questions about how the immune system perceives, responds, contains and eliminates these pathogens. One model to be studied is virulent Mycobacterium tuberculosis delivered via aerosol to the lungs of mice. This organism can survive inside vacuoles within macrophages and set up a chronic infection which can be contained, but not eliminated, by adaptive CD4+T cell immunity. The role of CD8+ T cells in controlling tuberculosis is controversial. Recombinant organisms producing a model antigen containing well-studied epitopes for CD4 and CD8 T cells will allow a study of the tempo of the T cell response, and provide new information on protection against what has been called the world's most successful pathogen..... M. tuberculosis may infect one third of the world's population. The second intracellular pathogen we plan to use is a common food-borne pathogen, Listeria monocytogenes. Excellent mouse models exist already for the study of this Gram positive pathogen, where it appears that adaptive CD8+ T cell immunity is the critical force in eliminating the infection. L. monocytogenes is a candidate vaccine vector for the induction of CD8 immunity, for example, against tumor antigens. The massive response of CD8+ T cells to acute infection with Listeria and the generation of long-lived protective immunity may also require CD4+ T cell help. The proposed studies are aimed at a greater understanding of the development of long-lived, protective immunity induced by this pathogen.

描述（由申请人提供）：我们的目标是研究CD4和CD8 T细胞对致病性感染剂的反应，以发现控制这些感染的T细胞生物学的基本原理。选择了两个对比的细胞内细菌病原体模型，以提出有关免疫系统如何感知，反应，包含和消除这些病原体的基本问题。一个要研究的模型是通过气溶胶传递到小鼠肺的有毒分枝杆菌结核病。这种生物可以在巨噬细胞内的液泡内生存，并通过自适应CD4+T细胞免疫来包含但不能消除的慢性感染。 CD8+ T细胞在控制结核病中的作用是有争议的。产生一种模型抗原的重组生物，该模型含有CD4和CD8 T细胞的表现良好的表位，将允许研究T细胞反应的速度，并提供有关针对世界上最成功的病原体的保护的新信息.....结核M. Tuberculculosis .....我们计划使用的第二种细胞内病原体是一种常见的食源性病原体，单核细胞增生李斯特菌。出色的小鼠模型已经存在于该革兰氏阳性病原体的研究中，在该病原体中似乎自适应CD8+ T细胞免疫是消除感染的关键力。单核细胞增生乳杆菌是一种候选疫苗载体，用于诱导CD8免疫，例如针对肿瘤抗原。 CD8+ T细胞对李斯特菌的急性感染和长期保护性免疫的大量反应也可能需要CD4+ T细胞帮助。拟议的研究旨在对这种病原体引起的长寿命，保护性免疫的发展有更深入的了解。