EXPRESSION OF ANTIMYCOBACTERIAL IMMUNITY

描述（改编自申请人的摘要）：SCID小鼠是 为拟议的实验模型。 这些小鼠不能进行T 细胞介导的免疫力，因此不能抵抗感染 与牛分枝杆菌的BCG菌株进行了比较。 然而，SCID小鼠可以是 从已经建立的BCG感染中拯救出来， 脾细胞或CD 4 + T细胞来自幼稚共基因C.B-17供体。 上 另一方面，SCID小鼠已经感染了强毒M.结核 更难抢救，尤其是肺部。 基于这些 根据观察，申请人建议（i）研究免疫学 在细胞和分子事件方面， 发生在已经确定的分枝杆菌感染部位， 目的是确定为什么肺部感染的抢救较少 比器官更有效率。 (ii)宿主细胞渗透到 将识别受感染的器官，确定它们的相对比例， 以及它们外渗的时间关系， 产生特异性CD 4 + T细胞介导的免疫。 收购 我们会监察特异性免疫力在迟发型超敏反应发展方面的情况， PPD、对二次激发的抗性和CD 4 + T细胞的存在 能够适应性免疫SCID接受者。 本申请人还提出鉴定由细胞粘附分子使用的关键粘附素分子。 CD 4 + T细胞进入感染部位，以及粘附分子使用 通过巨噬细胞进入这些部位形成肉芽肿， 随着时间的推移，它们的完整性。 这种方法将涉及使用 抗主要白细胞整合素及其配体的单克隆抗体 试图阻止肺部和其他地方的免疫表达。 肉芽肿中的巨噬细胞活化与感染抢救相关 将根据活性氮中间体的生产来衡量 的表达。

DESCRIPTION (Adapted from the applicant's abstract): SCID mice are the model for the proposed experiments. These mice are incapable of T cell-mediated immunity and are therefore incapable of withstanding infection with the BCG strain of Mycobacterium bovis. However, SCID mice can be rescued from an already established BCG infection by infusing them with spleen cells or CD4+ T cells from naive coisogenic C.B-17 donors. On the other hand, SCID mice already infected with virulent M. tuberculosis are more difficult to rescue, particularly in the lungs. Based on these observations, the applicant proposes (i) to study the immunological mediation of this rescue in terms of the cellular and molecular events that occur at sites of already established mycobacterial infection, with the purpose of determining why rescue of infections in the lungs are less efficient than in the organs. (ii) The host cells that extravasate into infected organs will be identified, their relative proportion determined, as well as the temporal relationship of their extravasation, with the generation of specific CD4+ T-cell mediated immunity. The acquisition of specific immunity will be monitored in terms of the development of DTH to PPD, resistance to secondary challenge, and the presence of CD4+ T cells capable of adaptively immunizing SCID recipients. The applicant also proposes to identify the key adhesin molecules used by CD4+ T cells to enter sites of infection, as well as adhesion molecules used by macrophages to enter these sites to form granulomas and to maintain the integrity of them over time. This approach will involve the use of monoclonal antibodies against major leukocyte integrins and their ligands in an attempt to block the expression of immunity in the lungs and elsewhere. Macrophage activation in granulomas associated with rescue from infection will be measured in terms of production of reactive nitrogen intermediates and Ia expression.