IMMUNE RESPONSE TO HERPES SIMPLEX VIRUS IN PREGNANCY

怀孕代表着一种部分免疫受损的状态 哪些感染是由疱疹等各种病原体引起的 单纯疱疹病毒(HSV)耐受性差。除了直接的 遇到产妇发病，可感染单纯疱疹病毒 传染给胎儿和新生儿，导致高度急性 围产儿死亡率与远期神经后遗症 幸存者。自然杀伤细胞细胞毒性(NKC)和抗体- 依赖性细胞毒性(ADCC)是主要的 被认为起关键作用的免疫防御系统 在单纯疱疹病毒感染中。这个项目的具体目标是 定义和描述怀孕期间的这些免疫反应。 使用体外效应/靶细胞模型，孕妇的 单核效应细胞将进行NKC和NKC系列检测 ADCC在整个妊娠过程中的活性，特别是针对HSV- 感染常肝靶细胞。根据申请人的 初步数据表明NKC在 怀孕，将使用单细胞琼脂糖法进一步 用其更基本的功能来定义这种缺陷 成分，即细胞黏附、裂解和回收。已知 免疫调节剂将在体外进行测试，以确定其能力 以重建这一与怀孕相关的NKC缺陷。 此外，对这一现象的机制进行了调查 发生免疫调节时，将通过检查 药理作用后的细胞花生四烯酸脂氧合作用 重建。这些目标的实现将有所改善 我们对儿童单纯疱疹病毒感染免疫学的认识 并提供了一种更合理的方法来应对 预防和控制这一传染性和病态的过程。 该提案概述的目标在后勤上是可以实现的，并且 将提供一个起点，开始我作为 这一研究领域的独立调查者。我最近的作品 史蒂夫·科尔博士为我提供了一项具有挑战性的研究 重点及其发展的方法论。我的两个人 赞助商和我的部门主任已经给了我明确的 这表明他们将继续支持这些努力。这 包括技术援助、实验室支持和足够的 从其他临床责任中解放出来。作为一个机构， 德克萨斯大学医学院因其 学术成就进一步凸显了这一点的丰富性 对于一个年轻的调查员来说，这是一个好环境。

Pregnancy represents a partially immunocompromised state in which infections caused by various pathogens such as herpes simplex virus (HSV) are poorly tolerated. Aside from the direct maternal morbidity encountered, HSV infections can be transmitted to the fetus and newborn resulting in a high acute perinatal mortality and long-term neurologic sequelae in survivors. Natural killer cell cytotoxicity (NKC) and antibody- dependent cellular cytotoxicity (ADCC) are primary immunodefense systems which are thought to play a pivotal role in HSV infection. The specific aims of this project set out to define and characterize these immune responses in pregnancy. Using an in vitro effector/target cell model, pregnant women's mononuclear effector cells will be serially tested for NKC and ADCC activity throughout gestation, specifically against HSV- infected Chang liver target cells. Based on the applicant's preliminary data which suggests an NKC deficient state in pregnancy, a single cell agarose assay will be used to further define this deficit in terms of its more basic functional components, i.e., cellular adhesion, lysis, and recycling. Known immunoregulatory agents will be tested in vitro for their ability to reconstitute this pregnancy-associated NKC deficit. Additionally, an investigation into the mechanism by which this immunoregulation occurs will be undertaken by examining cellular arachidonic acid lipoxygenation following pharmacologic reconstitution. Achievement of these objectives will improve our understanding of the immunology of HSV infection in pregnancy and provide a more rational approach to the prevention and control of this infectious and morbid process. The goals outlined to this proposal are logistically obtainable and would provide a starting point to begin my development as an independent investigator in this field of study. My recent work with Dr. Steve Kohl has provided me with a challenging research focal point and the methodology to develop it. Both my sponsors, and my department chairman, have given me clear indications of their continued support in these endeavors. This includes technical assistance, laboratory support, and adequate freedom from other clinical responsibilities. As an institution, The University of Texas Medical School is well recognized for its academic achievements further emphasizing the richness of this environment for a young investigator.