EXPRESSION OF ANTIMYCOBACTERIAL IMMUNITY

描述(改编自申请人的摘要)：SCID小鼠是 为拟议的实验建立模型。这些小鼠没有T细胞的能力 细胞免疫，因此不能抵抗感染 与牛分枝杆菌的卡介苗菌株。然而，SCID小鼠可以 从已经确定的卡介苗感染中解救出来，给他们注射 来自幼稚同基因C.B-17捐献者的脾细胞或CD4+T细胞。论 另一方面，已经感染了致病性结核分枝杆菌的SCID小鼠 更难抢救，尤其是在肺部。基于这些 观察，申请人建议(I)研究免疫学 在细胞和分子事件方面的这种救援的调解 发生在已经确定的分枝杆菌感染部位， 确定为什么抢救肺部感染较少的目的 比在器官里更有效率。(Ii)渗入的宿主细胞 被感染的器官将被识别，其相对比例被确定为 以及它们渗出的时间关系，与 产生特异性的CD4+T细胞介导的免疫。收购 将根据DTH的发展情况监测特异性免疫 PPD，对二次攻击的抵抗力，以及CD4+T细胞的存在 能够对SCID接受者进行适应性免疫。 申请者还建议确定由 进入感染部位的CD4+T细胞以及使用的黏附分子 巨噬细胞进入这些部位形成肉芽肿并维持 随着时间的推移，他们的正直。这种方法将涉及到使用 抗主要白细胞整合素及其配体的单抗 试图阻止免疫在肺部和其他地方的表达。 肉芽肿中巨噬细胞的激活与感染的抢救有关 将以活性氮中间体的产量来衡量 和Ia表情。

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.