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CELL-MEDIATED IMMUNITY IN INFLUENZA

CELL-MEDIATED IMMUNITY IN INFLUENZA
流感中的细胞介导的免疫
批准号:
3144450
负责人:
PETER C DOHERTY
金额:
$23.26万
依托单位国家:
美国
项目类别:
财政年份:
1990
资助国家:
美国
项目状态:
已结题
起止时间:
1990-04-01 至 1995-03-31

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项目成果

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中文摘要
翻译
其目的是开发一个互动模型,了解免疫系统如何 用来治疗呼吸道感染, 关于细胞介导免疫(CMI)的本质的想法。 最初的目标是 对局部淋巴细胞的变化进行严格的分析 淋巴结和肺部炎性渗出物。 这 实验系统将提供评估的基础 消除特定淋巴细胞亚群、细胞因子或 T细胞库的片段。 将检查的参数 包括淋巴细胞募集模式的改变, 特异性效应子功能,克隆扩增的调节, T细胞的分化和非特异性元件的参与, 主持人的回答。 我们需要了解这些不同的细胞 人群聚集在一起,以促进有效的免疫力。 技术 进行这种分析所需的资料现已备妥。 初步 小鼠流感研究表明, 特异性和效应子能力可用于开发定量的 了解纵隔淋巴结中的总CMI反应, 肺 这里所强调的是, 生物技术,如生产大量重组 细胞因子和中和性单克隆抗体, 来操纵免疫反应 然而,应用 治疗方案涉及接种大剂量的 淋巴因子已经表明,这种治疗的后果是 复杂且不为人知。 同样显而易见的是, 从淋巴细胞体外研究中得出的假设 文化系统不能以一种天真的方式翻译, 完整的宿主 很明显,我们需要发展一种 系统,在体内观察宿主反应,在一个全面的, 严格的方式。 当代表型和 在这里,还没有尝试对流感进行功能分析 以前的任何呼吸道感染,并已给予独特的 确定CMI的交互式事件的图片。 实验结果 对理解宿主对病毒的反应具有广泛的意义。
英文摘要
The intention is to develop an interactive model of how the immune system operates to deal with a respiratory infection, and to use this to test ideas about the nature of cell-mediated immunity (CMI). The initial aim is to make a rigorous analysis of the cellular changes in the regional lymph node and lung inflammatory exudate of mice with influenza. This experimental system will then provide the basis for assessing the consequences of eliminating particular lymphocyte subsets, cytokines or segments of the T cell repertoire. The parameters that will be examined include modification of lymphocyte recruitment patterns, the generation of specific effector functions, regulation of the clonal expansion and differentiation of T cells and the involvement of non-specific elements of the host response. The need is to understand how these various cell populations fit together to promote effective immunity. The technology that is required to make such analyses is now available. Preliminary studies of influenza in the mouse demonstrate assessment of lymphocyte specificity and effector capacity can be used to develop a quantitative understanding of the total CMI response in the mediastinal lymph node and the lung. The emphasis taken here depend on the fact that recent advances in biotechnology, such as the capacity to produce large amounts of recombinant cytokines, and neutralizing monoclonal antibodies, offer immense potential for manipulating the immune response. However, the application of therapeutic protocols that involve the inoculation of massive doses of lymphokines has indicated that the consequences of such treatments are both complex and poorly understood. It is also apparent that many of the postulates that have been developed from in vitro studies in lymphocyte culture systems cannot be translated in a naive way to the situation in the intact host. There is obviously a major need for the development of model systems that look at the host response in vivo in a comprehensive and rigorous way. The combined application of contemporary phenotypic and functional analysis used here for influenza has not been attempted previously for any respiratory infection, and is already giving a unique picture of the interactive events that determine CMI. The experiments have broad implications for understanding the host response to viruses.
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