IMMUNOLOGIC CONSEQUENCES OF M TUBERCULOSIS VIRULENCE

所提出的实验是基于这样的前提，即所有有毒的 菌株M.结核病（Mtb）能够持续存在并导致 进行性疾病的小鼠肺部在面对的机制T 能够解决其他器官感染的细胞介导免疫。它 建议记录一些标准参考菌株的毒力 结核分枝杆菌和一些最近分离的菌株在小鼠中。毒力将是 根据（a）肺中菌株的倍增时间进行评估， (b)他们的能力，逐步增长，并导致进行性病理， 肺，以及（c）它们杀死宿主所需的时间。将 确定是否在接种Mtb后确定毒力等级 当通过气溶胶给予菌株时，菌株IV适用。还将 确定BCG疫苗接种的小鼠是否更有能力处理 结核分枝杆菌菌株的毒力较低，毒力较高。的 将研究介导免疫的T细胞的特性， 确定CD 4 + T细胞是否主要负责，以及 它们可以单独介导免疫。有了这些信息， 将进行实验，以确定为什么免疫力 肺内CD 4 + T细胞介导的免疫调节不能完全控制感染 在这个器官里。这将涉及试图确定是否结核分枝杆菌- 特异性CD 4 + T细胞聚集在肺结核感染部位， 比它们在BCG感染部位积累的数量少， 不成功的免疫表达是否与 产生较低数量的T辅助细胞1特征性细胞因子 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.