T Cell Memory and Protection Against Placental Malaria

描述：(申请人提供)：疟疾高发地区的妇女 这些地区在怀孕期间感染疟原虫的风险增加。这个 寄生虫血症的患病率和密度在原始虫科中最高， 通常会导致产妇贫血和出生体重过低。胎盘是 尤其容易感染，寄生虫密度经常 高于外周血中的含量。人类免疫缺陷病毒的潜在免疫学基础 孕妇(及其胎盘)对疟疾的易感性增加 而这种易感性对妊娠的依赖程度还知之甚少。 这项应用的目的是确定细胞免疫 调节对胎盘疟疾抗药性的机制。中心假说 这一建议的一个好处是，多胎妊娠的易感性降低 胎盘感染依赖于组织特异性T细胞的发育 胎盘血中抗疟疾的细胞介导的记忆免疫反应。 其具体目的是：1)表征细胞介导的免疫记忆。 并确定有助于保护胎盘免受感染的因素 胎盘性疟疾，以及2)确定趋化因子在调节 胎盘对疟疾感染的记忆免疫反应。比较 在分娩时用流式细胞仪采集的外周和胎盘血样， ELISPOT、EL ISA、核糖核酸酶保护试验及胎盘检查 组织采用免疫组织化学方法，将用于1)鉴定表型 胎盘细胞记忆对疟疾反应的功能成分 区分多胎和初孕病毒科，易感女性从 抗药性妇女和保护性反应的致病反应，2) 确定这些胎盘反应与那些反应的不同程度 以及3)确定局部趋化因子的差异性 胎盘中的表达模式影响记忆免疫反应 胎盘性疟疾。扩大保护性、抗疟疾免疫知识 在免疫调节状态下发展和维持的机制 怀孕将促进免疫工具的应用，如疟疾。 疫苗在可用时，用于预防和控制疟疾 在孕妇身上。在孕妇中预防疟疾将显著 减少发展中世界妇女的疾病负担和减少 出生后头几个月的婴儿。

DESCRIPTION: (provided by the applicant): Women living in high malaria endemic areas are at an increased risk for Plasmodial infection during pregnancy. The prevalence and density of parasitemia is highest among primigravidae, and commonly leads to maternal anemia and low birth weight. The placenta is especially susceptible to infection, with parasite densities being frequently higher than those in the peripheral blood. The underlying immunologic basis for the increased susceptibility of pregnant women (and their placentae) to malaria and the dependence of this susceptibility on gravidity are poorly understood. The objective of this application is to determine the cellular immune mechanisms that mediate resistance to placental malaria. The central hypothesis of this proposal is that the decreased susceptibility of multigravidae to placental infection is dependent on development of tissue-specific, T cell-mediated, memory immune responses against malaria in the placental blood. The specific aims are to 1) to characterize cell-mediated immune memory in the placenta and identify the elements that contribute to protection against placental malaria, and 2) determine the role of chemokines in the regulation of memory immune responses against malarial infection in the placenta. Comparison of peripheral and placental blood collected at delivery using flow cytometry, ELISPOT, ELISA, and RNase protection assays, and examination of placental tissue using immunohistochemistry, will be used to 1) identify the phenotypic and functional components of placental cellular memory responses to malaria that distinguish multigravidae from primigravidae, susceptible women from resistant women, and pathogenic responses from protective responses, 2) determine the extent to which these placental responses are distinct from those in the peripheral blood, and 3) determine how differential, local chemokine expression patterns in the placenta influence memory immune responses to placental malaria. Expanded knowledge of protective, anti-malarial immune mechanisms that are developed and maintained in the immunomodulated state of pregnancy will facilitate application of immunologic tools, such as malaria vaccines when they become available, to the prevention and control of malaria in pregnant women. Preventing malaria in pregnant women will significantly reduce both the disease burden of women in the developing world and the loss of infants in their first few months of life.