CELL BIOLOGY OF THE IMMUNE RESPONSE TO BACTERIA

对细菌免疫反应的细胞生物学

• 批准号: 3480603
• 负责人: PRISCILLA A CAMPBELL
• 金额: $ 13.77万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480603
• 关键词: Listeria; T lymphocyte; bacterial antigens; bactericidal immunity; cell biology; cellular immunity; chemotaxis; flow cytometry; gel electrophoresis; humoral immunity; inflammation; interferons; interleukin 2; lymphokines; macrophage; macrophage activating factor; microorganism immunology; migration inhibition factor; monoclonal antibody; neutrophil; phagocytes; phagocytic dysfunction; phagocytosis

Over the past grant period, we have generated considerable data which implicate inflammatory phagocytes as an important component of resistance to infection by facultative intracellular bacteria. Using murine resistance to the facultative intracellular bacterium, Listeria monocytogenes, as a model system, we have shown that T cells which transfer resistance from immune mice to normal mice also transfer the ability to accumulate inflammatory macrophages and neutrophils in response to antigenic challenge. Inflammatory peritoneal neutrophils and macrophages are bactericidal; resident cells are not. Other studies show that the major defect in mice genetically-susceptible to listeria is in their ability to accumulate cells at the site of infection. Finally, macrophages can be selectively stimulated to express tumoricidal but not bactericidal activity, or bactericidal but not tumoricidal activity. Tumoricidal activity by activated macrophages can be dissociated from bactericidal activity. Based on these and other findings, we now wish to test the hypothesis that the major way in which T cells mediate resistance to facultative intracellular bacteria is by causing an influx of inflammatory phagocytes which are inherently bactericidal. It is possible they also enhance the ability of these cells to kill bacteria. To test this hypothesis, we will pursue four specific aims. First, we will clone listeria-reactive T cells and test them for production of biologically-active secretory products which contribute to resistance by enhancing recruitment of inflammatory responses. Second, we will determine whether genetically-susceptible mice have defects at the level of the T cell, the responding inflammatory phagocyte, or both. Third, we will determine whether gamma-interferon can stimulate macrophages to become bactericidal, and whether it can directly or indirectly enhance accumulation of inflammatory bactericidal phagocytes. Finally, we will continue to evaluate biologic properties of listeria components, with an emphasis on identifying and isolating the materials which cause inflammatory responses. It is expected that these studies will contribute to our understanding of how T cells mediate resistance to facultative intracellular bacteria, and perhaps to other microorganisms as well.

在过去的补助金期间，我们已经产生了大量的数据， 表明炎性吞噬细胞是抵抗的重要组成部分 被兼性细胞内细菌感染 使用鼠 对兼性胞内细菌李斯特菌的抗性 作为一个模型系统，我们已经表明，转移单核细胞的T细胞， 免疫小鼠对正常小鼠的抵抗力也转移了 积聚炎症巨噬细胞和中性粒细胞， 抗原攻击 炎症性腹膜中性粒细胞和巨噬细胞 是杀菌的，而常驻细胞不是 其他研究表明， 在遗传上易受疟原虫感染的小鼠中， 在感染部位积聚细胞的能力。 最后，巨噬细胞 可以被选择性地刺激以表达杀肿瘤但不杀菌的 活性，或杀菌活性但不杀肿瘤活性。 杀肿瘤 活化的巨噬细胞的活性可以与杀菌作用分离， 活动 基于这些和其他发现，我们现在希望检验以下假设： T细胞介导对兼性免疫应答的主要方式是， 细胞内细菌是通过引起炎性吞噬细胞的流入 其本身是杀菌的。 它们也可能增强 这些细胞杀死细菌的能力。 为了验证这个假设，我们将 实现四个具体目标。 首先，我们将克隆出一种能与大肠杆菌反应的T细胞， 并测试它们是否产生生物活性分泌产物 其通过增强炎性细胞的募集而有助于抵抗 应答 其次，我们将确定遗传易感小鼠是否 在T细胞水平上有缺陷， 吞噬细胞或两者。 第三，我们将确定γ-干扰素是否能 刺激巨噬细胞成为杀菌，以及它是否可以直接 或间接增强炎症性杀菌剂的积累 吞噬细胞 最后，我们将继续评估 的组成部分，重点是识别和分离 引起炎症反应的物质。 预计这些 研究将有助于我们理解T细胞如何介导 对兼性细胞内细菌的抗性，以及可能对其他细菌的抗性， 微生物也是。