PATHOGENESIS OF CHRONIC LUNG DISEASE

肺泡巨噬细胞构成了肺组织内的第一道防线 肺对一些兼性的细胞内寄生虫有抵抗力。其中一个 其中最重要的是结核杆菌。这项研究将检查 这些滞留的吞噬细胞及其移居所起的作用 进入发育中的肺结节的单核对应物 大量表达和调节期间的免疫反应。 这项研究的具体目的是为了了解 发生在慢性感染肺内的细胞相互作用 初级阶段继续生存悖论的一种尝试 肺及其引流淋巴结内的分枝杆菌种群 保护性细胞介导性免疫的明显证据是 在网状内皮系统的其他地方表达。这种状态 对于感染了堪萨斯氏支原体或支原体的小鼠，情况似乎尤其如此。 西米亚。这项研究的第一个目的将是检查T细胞的作用 迟发型超敏反应诱导和表达中的亚群 产气性感染宿主体内的抗结核免疫。这个 T细胞反应将在过继免疫的肺内进行测量， T细胞耗尽的小鼠使用淋巴细胞，其特征是 Lyt 1+或ly23+表面标记。这部分人口的相对构成 将与它们的功能特征相关联，例如表达， 记忆，或抑制细胞活动，在超敏和无能 捐赠者。第二个目标将是确定收养的效果 T细胞转移对单核细胞反应动力学的影响 单侧脉搏异生小鼠肺。免疫T细胞的作用 慢性感染肺泡组织内巨噬细胞活化的研究 将在激活时根据它们的杀伤力进行检查 巨噬细胞被非典型分枝杆菌感染。最后，老鼠 会被一种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 体外培养。免疫原呈现时增加剂量的效果 在不同的佐剂制剂中对小鼠的影响 迟发型超敏反应、获得性抗性和耐受性诱导。 这样的研究将提供对细胞相互作用的进一步见解 参与了肺内宿主反应的调节 感染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.