CELL-MEDIATED IMMUNITY IN INFLUENZA

其目的是开发一种交互模型，说明免疫系统如何 操作来处理呼吸道感染，并用它来测试 关于细胞免疫(CMI)本质的观点。最初的目标是 要对区域淋巴的细胞变化进行严格的分析 流感小鼠结节和肺炎性渗出物。这 然后，实验系统将为评估 消除特定淋巴细胞亚群、细胞因子或 T细胞谱系的片段。将检查的参数 包括修改淋巴细胞招募模式，产生 特异性效应器功能，克隆性扩张的调节和 T细胞的分化及其非特异性成分的参与 主机响应。我们需要了解这些不同的细胞是如何 种群相互配合，以促进有效免疫。技术 进行这样的分析所需的信息现在已经可用。初步 对小鼠流感的研究证明了淋巴细胞的评估 特异性和效应器能力可以用来开发一种定量的 纵隔淋巴结和纵隔淋巴结CMI总反应的认识 肺部。 这里所强调的是这样一个事实，即 生物技术，例如生产大量重组人的能力 细胞因子和中和性单抗提供了巨大的潜力 操纵免疫反应。然而，应用程序 治疗方案包括接种大剂量的 淋巴因子已经表明，这种治疗的后果既有 很复杂，也很难理解。同样明显的是，许多 从淋巴细胞体外研究中发展出来的假设 文化系统不能以幼稚的方式翻译成 完好无损的宿主。显然，模型的发展有很大的需求 在体内观察宿主反应的系统 严谨的方式。当代表型和表型的联合应用 这里使用的流感的功能分析还没有尝试过 以前对于任何呼吸道感染，已经给出了一个独特的 确定CMI的交互事件的图片。这些实验已经 对于理解宿主对病毒的反应具有广泛的意义。

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.