INFECTION MODEL OF LEPROMATOUS LEPROSY

麻风病感染模型

• 批准号: 3566205
• 负责人: FRANK M. COLLINS
• 金额: $ 15.93万
• 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/3566205
• 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.

鸟分枝杆菌复合体可产生进行性全身性 易感品系小鼠（C57 BL/6或BALB/c）感染 类似于人类瘤型麻风， 方便的实验模型来研究 抗麻风反应的免疫学。 不同的角色 这个过程中的T细胞亚群现在可以采用 接受特异性T细胞亚群并克隆的免疫动物 T细胞 后者为研究这一问题提供了重要的线索 表位的性质，负责诱导延迟 超敏反应和获得性耐药性。 的 第一个目的是研究T细胞应答的动力学， DTH和CMI在M.细胞内的鸟 感染，以及T细胞记忆诱导，使用两种T细胞系 和克隆（人和鼠）。 易感者与 将使用以下方法定量比较耐药小鼠品系： 适当的收养转移模式。 将试图 尽可能从功能方面评估T细胞克隆。 的 第二个目标将继续研究， 严重感染的肺、脾内的巨噬细胞活化 或足垫后感染的亚怀疑，耐药小鼠与 强毒和弱毒M. avium 拟议的研究将 比较了不同浓度和浓度的 常驻、免疫和免疫增强的巨噬细胞均进行了测试 在体外和体内对抗多种不同的测试生物体。 体外加入的淋巴因子激活巨噬细胞， 与体内活化细胞相比。 第三个目标将审查 M.结核和M. aviumintracellualare激活T细胞克隆来源于 免疫和结核菌素敏感宿主。 敏化素将是 通过HPLC和Western印迹分离并测试其 在接种疫苗的小鼠中诱导DTH应答的能力，以及 通过体外测试的T细胞克隆的母细胞生成应答。 敏化素 将通过与绵羊红细胞偶联作为免疫原进行测试， 硝酸纤维素膜或活卡介苗，并进行DTH测试 和CMI。 这些研究将提供有关 慢性感染者细胞介导免疫的恢复 小鼠