THE REGULATION OF NONTUBERCULOUS IMMUNITY

非结核免疫的调节

• 批准号: 3444466
• 负责人: FRANK M. COLLINS
• 金额: $ 14.83万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3444466
• 关键词: Mycobacterium; Mycobacterium avium; Mycobacterium intracellulare; Mycobacterium tuberculosis; T lymphocyte; athymic mouse; bacterial antigens; clone cells; delayed hypersensitivity; disease /disorder model; enzyme linked immunosorbent assay; fluorescence microscopy; gel electrophoresis; genetic strain; granuloma; high performance liquid chromatography; host organism interaction; human tissue; immune tolerance /unresponsiveness; immunity; immunization; immunomodulators; interferons; interleukin 2; laboratory mouse; leukocyte activation /transformation; lung; macrophage; macrophage activating factor; microorganism immunology; monoclonal antibody; radiation immunosuppression; spleen; superoxides; suppressor T lymphocyte; thymectomy; tuberculin test; virulence

Mycobacterium avium-complex can produce progressive systemic infections in susceptible strains of mice (C57BL/6 or BALB/c) which resemble human lepromatous leprosy, providing a convenient experimental model with which to study the immunology of the antileprosy response. The role of different Tcell subsets in this process can now be defined in adoptively immunized animals receiving specific Tcell subsets and cloned Tcells. The latter provide an important probe for investigating the nature of the epitopes responsible for the induction of delayed hypersensitivity and acquired resistance in the infected host. The first aim is to study the kinetics of the Tcell response leading to the expression of DTH and CMI to M. aviumintracellulare infections, and to T-cell memory induction, using both T-cell lines and clones (human and murine). T-cell responses in susceptible vs. resistant mouse strains will be compared quantitatively using appropriate adoptive transfer models. Attempts will be made to assess T-cell clones in functional terms wherever possible. The second aim will continue studies examining the number and activation of macrophages within the heavily infected lung, spleen or footpad following infection of subsceptible, resistant mice with virulent and attenuated M. avium. The proposed studies will compare the phagocytic activity and bactericidal ability of resident, immune and immuneboosted macrophages tested both in vitro and in vivo against a variety of different test organisms. Activation of macrophages by lymphokines added in vitro will be compared with in vivo activated cells. The third aim will examine the ability of protein sensitins from M. tuberculosis and M. aviumintracellualare to activate Tcell clones derived from immune and tuberculin sensitive hosts. The sensitin(s) will be separated by HPLC and Western blotting and tested for their ability to induce DTH response in vaccinated mice, as well as blastogenic responses by Tcell clones tested in vitro. Sensitins will be tested as immunogens by coupling to sheep erythrocytes, to nitrocellulose membranes or to live BCG and tested for DTH and CMI. These studies will provide valuable new data on the restoration of cellmediated immunity in chronically infected mice.

鸟型分枝杆菌复合体可产生进行性系统性 易感品系小鼠(C57BL/6或BALB/c)的感染 类似于人类麻风病，提供了一种 一种方便快捷的实验模型 抗麻风反应的免疫学。不同的角色 这一过程中的T细胞亚群现在可以通过 获得特异性T细胞亚群的免疫动物并克隆 T细胞。后者为调查提供了一个重要的探索 诱导延迟的表位的性质 感染宿主的过敏性和获得性抗性。这个 第一个目标是研究导致T细胞反应的动力学 DTH和CMI基因在航空航天微囊藻中的表达 感染，并使用两种T细胞系诱导T细胞记忆 和克隆人(人和鼠)。易感与非易感人群的T细胞反应。 耐药小鼠品系将通过使用 适当的采用迁移模式。我们将尝试 尽可能从功能的角度评估T细胞克隆。这个 第二个目标将继续研究检查数字和 严重感染的肺、脾内巨噬细胞的激活 或足垫感染不敏感、耐药的小鼠 毒力强、致弱的禽类分支杆菌。拟议的研究将 比较其吞噬活性和杀菌能力 驻留的、免疫的和免疫增强的巨噬细胞都进行了测试 在体外和体内对抗各种不同的试验微生物。 体外加入淋巴因子对巨噬细胞的激活作用 与体内激活的细胞相比。第三个目标将检查 结核分枝杆菌和结核分枝杆菌蛋白感受素的能力。 禽流感病毒激活来源T细胞克隆 免疫和结核菌素敏感宿主。敏感素(S)将是 经高效液相色谱和Western blotting分离并检测其活性 在接种疫苗的小鼠中诱导迟发型超敏反应的能力以及 体外测试T细胞克隆的胚胎性反应。Sensitins 将通过偶联绵羊红细胞作为免疫原进行测试， 硝酸纤维素膜或活体卡介苗并检测迟发型超敏反应 和CMI。这些研究将提供有价值的关于 慢性感染患者细胞免疫功能的恢复 老鼠。