PATHOGENESIS OF CHRONIC LUNG DISEASE

肺泡巨噬细胞构成肺内的第一道防线， 肺对一些兼性细胞内寄生虫。 之一 其中最重要的是结核杆菌。 本研究将探讨 这些驻留吞噬细胞和它们的迁移细胞所起的作用 单核细胞计数器，进入发育中的肺结节， 在免疫应答的表达和调节过程中大量表达。 本研究的具体目的是为了了解 在慢性感染的肺内发生的细胞相互作用， 试图解释初选继续生存的悖论 肺及其引流淋巴结内的分枝杆菌种群， 保护性细胞介导的免疫力的明确证据， 在网状内皮系统的其他地方表达。 的这种状态 这种情况在感染M. kansasili或M. 猿猴。 本研究的第一个目的将是检查T细胞的作用 在迟发型超敏反应的诱导和表达中的亚群， 抗结核免疫在产气感染的主机。 的 将在过继免疫的小鼠的肺内测量T细胞应答， 使用淋巴细胞的T细胞耗竭小鼠，其特征在于其 Lyt 1+或Ly 23+表面标记。 这群人的相对构成 将与它们的功能特征相关，例如表达器， 记忆，或抑制细胞的活动，在过敏性和无反应性 捐助者。 第二个目标是确定收养的影响。 T细胞转移对单核细胞反应动力学的影响 单侧脉冲的异种小鼠肺。 免疫T细胞的作用 对慢性感染肺泡组织内巨噬细胞活化的影响 将在它们的杀伤活性方面进行检查， 巨噬细胞被非典型分枝杆菌感染。 最后，老鼠 将被细胞外蛋白免疫原致敏， 由活跃繁殖的分枝杆菌在体内和体内释放， 体外 当免疫原出现时，增加免疫原剂量的效果 将根据以下方面评估不同佐剂制剂对小鼠的 迟发型超敏反应、获得性抗性和耐受诱导。 这些研究将为细胞相互作用提供进一步的见解， 参与调节肺内的宿主反应， 感染了这些重要的人类病原体之一

The alveolar macrophage constitutes the first line of defense within the lung against a number of facultative intracellular parasites. One of the most important of these is the tubercle bacillus. This study will examine the role played by these resident phagocytic cells and their emigrant mononuclear counter parts, which enter the developing lung tubercle in large numbers during the expression and modulation of the immune response. The specific aims of this study are directed towards understanding the cellular interactions which occur within the chronically infected lung in an attempt to explain the paradox of continued survival by the primary mycobacterial population within the lung and its draining lymph nodes, in the face of clear evidense of a protective cell-mediated immunity being expressed elsewhere in the reticuloendothelial system. This state of affairs seems particularly true for mice infected with M. kansasili or M. simiae. The first aim of this study will be to examine the role of T-cell subsets in the induction and expression of delayed hypersensitivity and antituberculous immunity within the aerogenically infected host. The T-cell responses will be measured within the lungs of adoptively immunized, T-cell depleted mice using lymphocytes characterized with respect to their Lyt 1+ or Ly 23+ surface markers. The relative makeup of this population will be correlated with their functional characteristics such as expressor, memory, or suppressor cell activity in both hypersensitive and anergic donors. The second objective will be to determine the effect of adoptive transfer of T-cells on the kinetics of the mononuclear cell response in unilaterally pulsed parabiotic mouse lungs. The effect of immune T-cells on macrophage activation within the chronically infected alvoelar tissues will be examined in terms of their killing activity when the activated macrophages are infected with the atypical mycobacteria. Finally, mice will be sensitized with an extracellular protein immunogen which is released by the actively multiplying mycobacteria, both in vivo and in vitro. The effect of increasing the dose of immunogen when it is presented to mice in different adjuvanting preparations will be assessed in terms of delayed hypersensitivity, acquired resistance and tolerance induction. Such studies will provide further insights into the cellular interactions involved in the modulation of the host response within the lung following an infection with one of these important human pathogens.