IMMUNITY TO CHLAMYDIAL GENITAL INFECTION

描述（改编自申请人的摘要）：沙眼衣原体是 可能是世界上最常见的性传播细菌病原体 在美国，泌尿生殖道沙眼衣原体的400万新病例 感染每年都会发生，据估计，治疗这些感染的费用 每年的感染费用接近40亿美元。泌尿生殖道感染由C. 沙眼导致许多不同的临床病症。感染 妇女的感染范围从急性自限性感染到更严重的感染， 导致盆腔炎、不孕和宫外孕。 在过去几年中，在以下方面取得了相当大的进展： 扩大我们对免疫反应的理解， 衣原体感染然而，我们对效应器机制的理解， 限制衣原体感染和防止再感染是不够的。的 研究者最近数据表明，CD 4 + T细胞和B细胞 （抗体）有助于获得性免疫衣原体生殖道 感染因此，本项目的总体目标是使用小鼠模型， C.沙眼衣原体生殖道感染与CD 4 + T细胞关系的研究 细胞和抗体对感染的适应性免疫。这个目标将是 通过4个具体目标中描述的研究实现：1）确定 免疫B细胞和抗体重建保护性免疫的能力 CD 4-耗尽的B细胞缺陷小鼠; 2）确定是否缺乏成熟的B 在B细胞基因敲除小鼠中， 衣原体特异性记忆T细胞反应; 3）确定 同时免疫细胞耗竭对获得性免疫的影响;以及4）评估 抗体和淋巴细胞对衣原体生长的抑制作用 体外（抗体依赖性细胞毒性）。这些研究将扩大 我们对宿主如何抵抗衣原体感染的理解， 对有效疫苗的配制和管理的新见解， 控制衣原体感染的传播或预防 发病机理

DESCRIPTION (Adapted from the Applicant's Abstract): Chlamydia trachomatis is possibly the most common sexually transmitted bacterial pathogen in the world. In the United States, 4 million new cases of C, trachomatis urogenital tract infection occur each year, and it is estimated that the cost of treating those infections approaches $4 billion annually. Urogenital infections caused by C. trachomatis result in a number of diverse clinical conditions. Infections in women range from acute self-limiting infections to more serious infections that result in pelvic inflammatory disease, infertility and ectopic pregnancy. Considerable progress has been made in the past few years to significantly broaden our understanding of immune responses that develop during the course of chlamydial infection. However, our understanding of effector mechanisms that limit chlamydial infection and prevent reinfection is insufficient. The investigator's recent data suggest that both CD4+ T cells and B cells (antibody) contribute to adaptive immunity to chlamydial genital tract infection. Thus the overall goal of this project is to use the murine model of C. trachomatis genital tract infection to study the relationship between CD4+ T cells and antibody in adaptive immunity to infection. That goal will be realized through the studies described in 4 specific aims: 1) To determine the ability of immune B cells and antibody to reconstitute protective immunity in CD4-depleted B cell deficient mice; 2) To determine if the lack of mature B cells in B cell gene knockout mice affects the development of chlamydial-specific memory T cell responses; 3) To determine the effect of simultaneous immune cell depletions on acquired immunity; and 4) To evaluate the inhibitory effects of antibodies and lymphocytes on chlamydial growth in vitro (antibody dependent cellular cytotoxicity). These studies will broaden our understanding of how the host resists chlamydial infection, and may provide new insights into the formulation and administration of an effective vaccine to control the spread of chlamydial infections or prevent the serious sequelae of disease pathogenesis.