IMMUNOPATHOLOGY OF MYCOBACTERIUM INTRACELLULARE IN AIDS

艾滋病细胞内分枝杆菌的免疫病理学

• 批准号: 3132377
• 负责人: PATTISAPU R GANGADHARAM
• 金额: $ 11.78万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132377
• 关键词: AIDS; Actinomycetales infection; Mycobacterium; bacterial antigens; bactericidal immunity; chemotaxis; cortisol; cyclophosphamide; delayed hypersensitivity; disease /disorder model; drug abuse; helper T lymphocyte; homosexuals; immunological substance; immunosuppressive; interferons; interleukin 2; macrophage; migration inhibition factor; prostaglandin E; secondary infection; superoxides; suppressor T lymphocyte; triiodothyronine

One of the most distressing and potentially serious health problems recently discovered in American life is the Acquired Immune Deficiency Syndrome (AIDS). In the short span of less than 3 years after the initial recognition, many patients have been discovered to have this syndrome. The agonizing and grim facts of the seriousness of the disease and very high mortality prompted several concerned agencies and individuals to launch a serious battle against this malady. AIDS patients become increasingly susceptible to life threatening infections, caused by several opportunistic microorganisms, which do, at the most cause only benign infection processes in normal individuals. This application concerns the immunopathologic studies with one of these, M. intracellulare. Unlike the other opportunistic microorganisms, M. intracellulare can cause a refractory, disseminated type of disease in non-AIDS patients as well. Following the earlier leads obtained from our laboratories, the suitability of the Beige mutants of C57B1/6 mice as a possible experimental animal model for AIDs patients with M. intracellulare infections will be investigated. Other attributes of the Beige mice, besides the evidence of their increased susceptibility to this infection, are the absence of natural killer (NK) cells, and increased suppressor cells - features established to be common in AIDS patients. An important aspect in this study is to assess the role of immunosuppressive and recreational drugs, commonly used by the AIDS patients, on the pathogenesis of this organism in this animal model, as judged by in vivo bacterial multiplication and mortality. In order to further characterize and strengthen the claims of this model, specific investigations on the immunomodulation of the host by way of assessment of prostaglandin (PGE2) and synthesis with its consequent influence on Interleukin-2 (IL-2) and gamma interferon (IFN). Protective studies in animals using indomethacin (inhibitor or prostaglandin synthesis), IL-2 and IFN will also complement the results of clinical studies with these agents, already in progress in this country. Finally, specific experiments aimed at characterization and quantitation of the T subset (T helper (TH) and T suppressor (TS) cell) populations and the TH:TS cell ratios in this mouse model, following infection with M. intracellulare will add further insight into the pathobiology of this syndrome and strengthen the suitability of this model.

最令人痛苦，最严重的健康问题之一 最近在美国生活中发现的是获得的免疫缺陷 综合征（艾滋病）。 在初始不到3年的短时间内 识别，许多患者被发现患有这种综合征。 这 疾病严重性和非常高的痛苦和严峻的事实 死亡率促使几个有关机构和个人发起 与这种疾病的严重战斗。 艾滋病患者变得越来越多 容易受到威胁生命感染的影响，这是由于几种机会主义的 微生物，最大的是仅引起良性感染过程 在普通人中。 该应用涉及免疫病理学 其中之一的研究，M。M。ellacelulare。 与另一个不同 机会性微生物，M。Elcellulare会引起难治性， 非AIDS患者的传播类型的疾病类型。 跟随 从我们的实验室获得的早期潜在客户，米色的适用性 C57B1/6小鼠的突变体作为AIDS的可能实验动物模型 将研究胞内感染分枝杆菌的患者。 其他 米色小鼠的属性，除了证据增加 对这种感染的敏感性是没有天然杀手（NK） 细胞和增加的抑制细胞 - 建立为常见的特征 在艾滋病患者中。 这项研究的一个重要方面是评估角色 免疫抑制和休闲药，艾滋病常用 患者，关于这种动物模型中这种生物的发病机理， 由体内细菌繁殖和死亡率判断。 为了 进一步表征和加强该模型的主张 通过评估对宿主进行免疫调节的调查的调查 前列腺素（PGE2）和合成及其对 白介素2（IL-2）和伽马干扰素（IFN）。 保护性研究 使用吲哚美辛（抑制剂或前列腺素合成），IL-2和 IFN还将与这些药物的临床研究结果补充， 这个国家已经在进行。 最后，针对特定的实验 在T表征和定量T子集时（T辅助（T）和T 抑制器（TS）细胞）种群和该小鼠中的TS细胞比率 模型，感染M. M. ellacululare将增加进一步的见解 进入该综合征的病理生物学，并增强 这个模型。