IMMUNITY TO CHLAMYDIAL GENITAL INFECTION

描述(摘自申请者摘要)：沙眼衣原体 可能是世界上最常见的性传播细菌病原体。 在美国，400万新的沙眼衣原体泌尿生殖道病例 感染每年都会发生，据估计，治疗这些疾病的成本 每年感染人数接近40亿美元。C.引起的泌尿生殖道感染 沙眼可导致多种不同的临床症状。中国的感染 女性从急性自限性感染到更严重的感染 导致盆腔炎、不孕症和异位妊娠。 在过去的几年里，已经取得了相当大的进展， 扩大我们对免疫反应的理解，这些反应是在 衣原体感染。然而，我们对效应器机制的理解 限制衣原体感染和预防再感染是不够的。这个 研究人员最近的数据表明，CD4+T细胞和B细胞 (抗体)有助于对衣原体生殖道的适应性免疫 感染。因此，该项目的总体目标是使用小鼠模型 沙眼衣原体生殖道感染与CD4+T细胞关系的研究 感染适应性免疫中的细胞和抗体。这一目标将是 通过4个具体目标描述的研究实现：1)确定 免疫B细胞和抗体重建保护性免疫的能力 2)确定缺乏成熟B细胞的小鼠 B细胞基因敲除小鼠中的细胞影响糖尿病的发生 衣原体特异性记忆T细胞反应；3)确定 同时免疫细胞耗尽对获得性免疫的影响；4)评估 抗体和淋巴细胞对沙眼衣原体生长的抑制作用 体外(抗体依赖的细胞毒性)。这些研究将拓宽 我们对宿主如何抵抗衣原体感染的理解，可能会提供 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严重的后遗症 疾病发病机制。

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.