PROCESSING OF MYCOBACTERIAL GLYCOPEPTIDOLIPID ANTIGENS

分枝杆菌糖肽脂抗原的加工

• 批准号: 3132463
• 负责人: William W Barrow
• 金额: $ 4.36万
• 依托单位: TEXAS COLLEGE OF OSTEOPATHIC MEDICINE
• 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/3132463
• 关键词: AIDS; Actinomycetales infection; B lymphocyte; Mycobacterium; T lymphocyte; autoradiography; bacterial antigens; bactericidal immunity; cell cell interaction; cellular immunity; glycolipids; immunochemistry; immunological substance; immunosuppression; leukocyte activation /transformation; macrophage; migration inhibition factor; phagocytosis; radiotracer; respiratory infections; secondary infection; surface antigens; thin layer chromatography

The main objective of this proposal is to investigate the processing of certain mycobacterial glycolipid antigens by host macrophages so that a better understanding of postphagocytic events in mycobacterial infections can be achieved. This objective will be accomplished by using radiolabeled glycopeptidolipid (GPL) antigens isolated from Mycobacterium intracellulare serovar 20 of the Mycobacterium avium-M. intracellulare- M. scrofulaceum (MAIS) serocomplex. The MAIS complex represents a group of nontuberculous mycobacteria which can cause severe lung infections in man and which more recently have been found to be important opportunistic pathogens in patients suffering from Acquired Immune Deficiency Syndrome (AIDS). The GPL antigens of serovar 20 will be radiolabeled by means of internal labeling techniques and used in conjunction with immunocytochemical procedures as probes to confirm and monitor their association with mouse peritoneal macrophages. Once postphagocytic association of the GPL antigens has been established, experiments will be initiated to investigate what effect GPL antigens have on macrophage function. These preliminary experiments, which will focus on the possibility that GPL antigens contribute to suppression of immune functions, will examine the effect of GPL antigens on lymphokine production and lymphocyte proliferation of mitogen stimulated lymphocytes. Because of the increasing evidence that antigens associated with macrophages can stimulate delayed hypersensitivity and in turn generate a more effective cell mediated immune response, the results of this investigation could have important implications with regards to host responses to mycobacterial infections associated with AIDS patients. If the GPL antigens can become associated with macrophages, future experiments will be designed to determine the effectiveness of the macrophage-associated antigens in eliciting cell mediated immune responses. Alternatively, localization of the GPL antigens within or on host macrophages might affect the proper communication between macrophages and other immunologically important cells such as B and/or T lymphocytes. As these cellular interactions are essential in proper immunological responsiveness to intracellular pathogens, an investigation of the postphagocytic events involving the GPL antigens might be important in understanding the lack of responsiveness that AIDS patients demonstrate to nontuberculous mycobacteria in the MAIS serocomplex.

本提案的主要目的是调查 某些分枝杆菌糖脂抗原通过宿主巨噬细胞， 更好地了解分枝杆菌感染中的吞噬后事件 可以实现。 这一目标将通过使用放射性标记的 从胞内分枝杆菌分离的糖肽脂（GPL）抗原 鸟型分枝杆菌20血清型M.胞内- M.淋巴结核 （迈斯）血清复合物。 迈斯复合体代表了一组非结核性 分枝杆菌，可导致严重的肺部感染的人， 最近已发现是重要的机会致病菌， 患有获得性免疫缺陷综合征（AIDS）的患者。 的 血清型20的GPL抗原将通过内标法进行放射性标记。 标记技术，并与免疫细胞化学 作为探针的程序，以确认和监测它们与小鼠的关联 腹膜巨噬细胞。 一旦吞噬后GPL的结合 抗原已经建立，实验将开始调查 GPL抗原对巨噬细胞功能的影响。 这些初步 实验，这将集中在GPL抗原， 有助于抑制免疫功能，将检查的影响， GPL抗原对小鼠淋巴因子产生和淋巴细胞增殖的影响 有丝分裂原刺激的淋巴细胞。 由于越来越多的证据表明，与 巨噬细胞可以刺激迟发性超敏反应， 更有效的细胞介导的免疫反应， 调查可能会对东道国产生重要影响， 与艾滋病患者相关的分枝杆菌感染的反应。 如果 GPL抗原可以与巨噬细胞结合，未来的实验 将被设计为确定的有效性， 巨噬细胞相关抗原在诱导细胞免疫中的作用 应答 或者，将GPL抗原定位在细胞内或细胞上， 宿主巨噬细胞可能影响巨噬细胞之间的正常通讯 和其它免疫学上重要的细胞如B和/或T淋巴细胞。 由于这些细胞相互作用在适当的免疫反应中是必不可少的， 对细胞内病原体的反应性， 涉及GPL抗原的吞噬后事件可能在 了解艾滋病患者对艾滋病病毒缺乏反应， 迈斯血清复合物中的非结核分枝杆菌。