IMMUNOLOGIC CONSEQUENCES OF M TUBERCULOSIS VIRULENCE

拟议的实验是基于这样一个前提，即所有具有毒性的 结核分枝杆菌菌株(结核分枝杆菌)能够持续存在并引起 面对T细胞机制的小鼠肺部进行性疾病 细胞免疫能够解决其他器官感染的细胞免疫。它 建议用来证明一些标准参考菌株的毒力 Mtb和一些最近在小鼠身上分离的菌株。致死性将会是 根据(A)肺部菌株的倍增时间进行评估， (B)其渐进性生长和导致进行性病理改变的能力 以及(C)它们杀死宿主所需的时间。会是 已确定接种结核分枝杆菌后是否确定毒力等级 菌株IV适用于以气雾剂给药的情况。它也将是 确定接种卡介苗的小鼠是否更有能力处理 结核分枝杆菌毒力低的菌株比毒力高的菌株。这个 将对介导免疫的T细胞的身份进行调查 确定是否主要由CD4+T细胞负责，以及 他们可以单独调解豁免权。有了这些信息， 将进行实验，以确定为什么豁免权 肺内由CD4+T细胞介导的感染未能完全控制感染 在这个器官里。这将涉及尝试确定结核分枝杆菌是否- 小鼠肺内结核分枝杆菌感染部位特异性CD4+T细胞积聚 比在卡介苗感染部位积累的数量更少，以及 免疫表达不成功是否与 辅助性T细胞1分泌低量细胞因子的研究 细胞。

The proposed experiments are based on the premise that all virulent strains of M. tuberculosis (Mtb) are capable of persisting and causing progressive disease in the lungs of mice in the face of a mechanism of T cell-mediated immunity capable of resolving infection in other organs. It is proposed to document the virulence of some standard reference strains of Mtb and some recently isolated strains in mice. Virulence will be assessed in terms of (a) the doubling times of the strains in the lungs, (b) their ability to grow progressively and cause progressive pathology in the lungs, and (c) the time it takes them to kill their hosts. It will be determined whether virulence ranking determined after inoculating Mtb strains iv applies when the strains are given by aerosol. It will also be determined whether BCG-vaccinated mice are more capable of dealing with Mtb strains of low virulence than strains of higher virulence. The identity of the T cells that mediate immunity will be investigated to determine whether CD4+ T cells are predominantly responsible, and whether they can mediate immunity alone. With this information in hand, experiments will be performed with a view to determining why the immunity mediated by CD4+ T cells in the lung fails to completely control infection in this organ. This will involve attempts to determine whether Mtb- specific CD4+ T cells accumulate at sites of Mtb infection in the lungs in smaller numbers than they accumulate at sites of BCG infection, and whether unsuccessful expression of immunity is associated with the production of lower quantities of cytokines characteristic of T helper 1 cells.