CHLAMYDIA AND GONOCOCCAL INFECTION--IMMUNOBIOLOGY OF FEMALE REPRODUCTIVE TRACT

越来越多的证据表明，免疫系统在介导对淋球菌和衣原体感染和疾病的抗性和易感性方面起着重要作用。然而，大多数对这些药物的免疫反应的病例对照研究中固有的缺陷限制了理解因果关系方向的能力。此外，衣原体和淋病及其专性宿主之间的许多相互作用发生在生殖道粘膜，但对这些生物体的粘膜免疫反应尚未完全研究。最后，大多数研究人员关注的是免疫防御对生物体的影响，而忽略了生物体对其他药物的免疫反应可能产生的影响。因此，提出的研究的双重目标是前瞻性地表征粘膜和全身免疫反应，介导对淋球菌和衣原体感染和疾病的保护或增强易感性；并研究淋球菌和衣原体感染如何改变粘膜对彼此和对艾滋病毒的免疫反应的机制。我们假设抗原特异性I型（干扰素γ）和2型（JL-4和IL-10）免疫应答之间的平衡决定了对衣原体和淋球菌感染和疾病的抗性和易感性，并改变了对其他性传播媒介感染的易感性。将对肯尼亚内罗毕的两组商业性工作者进行随访，以了解是否感染淋球菌和衣原体，以及是否发生组织学证实的盆腔炎。事件和PID的关系将与抗原特异性免疫反应的基线测量相关。淋球菌和衣原体感染引起的粘膜免疫反应与其他病原体引起的感染和疾病的易感性之间的关系将通过描述当前感染个体和治疗后4至6周的下生殖道（包括子宫内膜）内的细胞因子和体液反应来评估。这些研究将阐明抵抗淋球菌和衣原体感染的特异性免疫反应，并与衣原体和淋球菌PID的发展相关。

Growing evidence suggests that the immune system plays an important role in mediating resistance and susceptibility to gonococcal and chlamydial infection and disease. However, inherent flaws in most case- control studies of immune response to these agents limit the ability to understand the direction of causality. Additionally, much of the interaction between chlamydia and gonorrhea and their obligate human hosts occurs at the genital tract mucosa, yet mucosal immune responses to these organisms have been incompletely studied. Lastly, most researchers focus on the effects of immune defenses to the organism, neglecting the effects that the organisms might have on immune responses to other agents. Thus, the twin goals of the proposed research are to prospectively characterize the mucosal and systemic immune responses that mediate protection against or enhancement of susceptibility to gonococcal and chlamydial infection and disease; and to examine the mechanisms by which gonococcal and chlamydial infections alter mucosal immune responses to each other and to HIV. We hypothesize that the balance between antigen specific type I (interferon gamma) and type 2 (JL-4 and IL-10) immune responses determine resistance versus susceptibility to chlamydial and gonococcal infection and disease, and modify susceptibility to infection with other sexually transmitted agents. Two cohorts of commercial sex workers in Nairobi, Kenya will be followed for acquisition of gonococcal and chlamydial infections, and the occurrence of histologically confirmed PID. The relationship of incident and PID will be correlated with baseline measurements of antigen specific immune responses. The relationship of mucosal immune responses evoked by gonococcal and chlamydial infection on susceptibility to infection and disease due to other pathogens will be evaluated by characterizing the cytokine and humoral responses within the lower genital tract including the endometrium among individuals currently infected and 4 to 6 weeks post treatment. These studies will elucidate the specific immune responses that characterize resistance to gonococcal and chlamydial infection, and which correlate with the development of chlamydial and gonococcal PID.