IMMUNOLOGY OF HUMAN CHLAMYDIAL INFECTIONS

沙眼衣原体是一种专性细胞内细菌病原体， 感染眼和生殖道粘膜，引起许多 临床上不同的综合征。尽管我们在这方面取得了重大进展， 了解衣原体的生物学和抗原结构，以及 衣原体疾病的流行病学和临床谱， 人类衣原体感染的发病率仍然很高， 重要公共卫生问题。衣原体疾病的控制将可能 依靠多学科方法，包括发展 免疫预防或免疫抑制策略。合理的进展 在理解特定的免疫机制， 衣原体感染实验模型中的宿主免疫力。然而，在这方面， 人类免疫力的研究并不那么成功。这是 特别明显的是，研究，以解决发展和作用 泌尿生殖道衣原体感染的粘膜免疫反应， 即将到来。因为衣原体感染，复制和造成损害， 粘膜上皮，研究需要检查的作用， 粘膜免疫应答的免疫保护作用。这个项目的总体目标是 项目是分析粘膜抗衣原体抗体反应， 在女性和男性生殖道感染后出现。这一目标 将通过三个具体目标来实现。最初的分泌和 将表征系统性抗衣原体抗体反应， 在有或没有衣原体生殖道的男性和女性中进行比较 感染抗衣原体抗体的亚类特异性 将确定反应并与感染性病毒的脱落进行比较。 生物体（具体目标#1）。血清的抗原特异性和 将通过免疫印迹分析分泌性抗体应答， 主要免疫球蛋白同种型的抗原特异性将是 具体目标#2）。分泌性抗体的功能作用 将使用体外中和试验进行评价。血清和 将比较分泌性中和抗体应答， 将确定中和抗体的免疫球蛋白亚类 （具体目标#3）。该项目与临床相关， 核心项目（Core B）、项目1（Hook）和项目2（Schwebke）将 提供关于生殖道衣原体免疫的有用信息 女性和男性的生殖道感染。此外，这些研究的结果 可能为设计有效的衣原体疫苗提供见解。

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the ocular and genital tract mucosa, to cause a number of clinically distinct syndromes. Despite significant advances in our understanding of the biology and antigenic structure of chlamydiae, and the epidemiology and clinical spectrum of chlamydial disease, the magnitude of morbidity from human chlamydial infections remains an important public health concern. Control of chlamydial disease will likely depend on a multidisciplinary approach, including the development of immunoprophylactic or immunotherapeutic strategies. Reasonable progress has been made in understanding specific immune mechanisms that contribute to host immunity in experimental models of chlamydial infection. However, studies of human immunity have not been so successful. This is particularly evident in that studies to address the development and role of mucosal immune responses to chlamydial urogenital infections having not been forthcoming. Because chlamydiae infect, replicate and cause damage to the mucosal epithelium, studies are needed that examine the role of mucosal immune responses in immune protection. The overall goal of this project is to analyze the mucosal anti-chlamydial antibody response that develops following genital tract infection of women and men. That goal will be achieved through 3 specific aims. Initially the secretory and systemic anti-chlamydial antibody responses will be characterized and compared in men and women with-or without chlamydial genital tract infection. The subclass specificity of the anti-chlamydial antibody response will be determined and compared to the shedding of infectious organism (specific aim #1). The antigenic specificity of the serum and secretory antibody responses will be analyzed by immunoblotting and the antigenic specificity of the predominant immunoglobulin isotypes will be determined (specific aim #2). A functional role for secretory antibodies will be evaluated using an in vitro neutralization assay. Serum and secretory neutralizing antibody responses will be compared, and the immunoglobulin subclass of the neutralizing antibodies will be determined (specific aim #3). This project, which is inter-related with the Clinical Core Project (Core B), Project 1 (Hook), and Project 2 (Schwebke), will contribute useful information regarding immunity to chlamydial genital tract infection in women and men. Furthermore, results from these studies may provide insight into the design of an effective chlamydial vaccine.