T Cell Memory and Protection Against Placental Malaria

描述：（由申请人提供）：生活在疟疾高发区的妇女 怀孕期间感染疟原虫的风险增加。的 寄生虫血症的患病率和密度在孕妇中最高， 通常会导致母亲贫血和低出生体重。胎盘 特别容易感染，寄生虫密度经常 高于外周血。潜在的免疫学基础 孕妇（及其胎盘）对疟疾的易感性增加 以及这种易感性对妊娠的依赖性知之甚少。 本申请的目的是确定细胞免疫 对胎盘疟疾产生抗性的机制。核心假设 这一建议的一个重要原因是， 胎盘感染依赖于组织特异性T 胎盘血液中的细胞介导的记忆免疫反应。 具体目的是：1）表征细胞介导的免疫记忆， 胎盘，并确定有助于保护免受 胎盘疟疾，和2）确定趋化因子在调节的作用， 胎盘中对疟疾感染的记忆免疫反应。比较 使用流式细胞术在分娩时收集外周血和胎盘血， ELISPOT、ELISA和RNA酶保护测定，以及胎盘 组织，将用于1）鉴定表型 和胎盘细胞对疟疾的记忆反应的功能成分 区分多次妊娠和多次妊娠，易感妇女和 耐药妇女，以及保护性反应的致病反应，2） 确定这些胎盘反应与那些不同的程度 在外周血中，以及3）确定如何区分，局部趋化因子 胎盘中的表达模式影响记忆免疫反应， 胎盘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 预防和控制疟疾 在孕妇中。孕妇预防疟疾将显著提高 减少发展中国家妇女的疾病负担， 婴儿在生命的最初几个月。

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.