MALARIA AND IMMUNE RESPONSES OF CORD BLOOD CELLS

恶性疟原虫引起的疟疾模式受到影响 由环境因素，包括地方性和强度， 变速箱。例如，居住在低流行区的儿童 通常患有以脑型疟疾为特征的严重疾病， 而居住在全流行地区的儿童更有可能 有与严重贫血相关的寄生虫血症经历。这是相当不错的 免疫过程可能会对 与寄生虫密度无关的疾病的临床表现 在血液中。因为胎盘是血液期的储存库 原虫抗原，我们假设母亲生下的婴儿 在怀孕期间经历疟疾会产生耐受性或抑制性 子宫内血液期抗原的作用机制。在随后的疟疾期间 感染，与年龄相关的保护性免疫的获得是 由T细胞谱系定义的，这是由早期的 暴露于疟疾抗原。我们建议受影响的新生儿 免疫反应是通过特征的表达来反映的 T细胞和单核细胞的表型标志和免疫功能 可从脐带血细胞中回收。 为了审查这些问题，我们提出了以下具体目标 初产妇分娩时采集的脐带血样本 冈比亚的妇女，在一个地方性疾病高发的地区 传播强度的季节波动：(1)确定T 脐血单个核细胞的细胞反应性不同于 合并疟疾的怀孕与怀孕期间 没有发生疟疾。分析将包括增殖的T细胞 对裂殖体感染的红色血液期抗原的反应 血细胞，或蛋白质和多肽抗原；淋巴因子谱 血液阶段抗原反应性T细胞；区分的T细胞亚群 通过细胞表面标志物对暴露于血液期抗原的反应。 (2)评估孕期感染疟疾是否会影响 脐带血单核细胞的成熟。这项分析将包括： 体外单核细胞淋巴因子谱的研究 患有和不患有疟疾的孕妇的脐带血；淋巴因子 用血液期抗原进一步体外刺激产生； 在相同条件下诱导细胞表面标记。 对这些早期反应的理解对未来的研究至关重要 试图阐明年龄相关保护的潜在机制 免疫，这是疟疾疫苗开发的一个关键点。

The patterns of malaria caused by Plasmodium falciparum are influenced by environmental factors, including endemicity and intensity of transmission. For example, children residing in hypoendemic areas commonly suffer from severe illness characterized by cerebral malaria, whereas children residing in holoendemic areas are more likely to experience parasitemia associated with severe anemia. It is quite possible that immune processes might have a profound impact upon the clinical manifestation of disease independent of the parasite density in the bloodstream. Since the placenta is a repository for blood-stage plasmodial antigens, we hypothesize that infants born to mothers who experience malaria during pregnancy develop tolerance or suppressive mechanism to blood stage antigens in utero. During subsequent malaria infections, the age-related acquisition of protective immunity is defined by the T cell repertoire that has been shaped by an early exposure to malaria antigens. We propose that the affected neonatal immune responses are reflected by the expression of characteristic phenotypic markers and immunologic functions of T cells and monocytes recoverable from cord blood cells. The following specific aims are proposed to examine these issues using cord blood specimens obtained at the time of delivery from primigravida women in The Gambia, in a region where high endemicity prevails with seasonal fluctuations in transmission intensity: (1) To determine if T cell reactivities of cord blood mononuclear cells differ between pregnancies complicated by malaria compared to pregnancies during which malaria did not occur. The analysis will include proliferative T cell responses to blood-stage antigens in the form of schizont-infected red blood cells, or protein and peptide antigens; lymphokine profiles of the blood-stage antigens-responding T cells; T cell subsets distinguished by cell surface markers in response to exposure to blood-stage antigens. (2) To evaluate if malaria infection during pregnancy affects the maturation of cord blood monocytes. This analysis will include: investigation of lymphokine profiles of ex vivo monocytes; obtained from cord blood from pregnancies with and without malaria; lymphokine production upon further in vitro stimulation with blood-stage antigens; induction of cell surface markers under the same conditions. Understanding of these early responses is essential for future studies seeking to elucidate mechanisms underlying age-related protective immunity, a pivotal point in the development of malaria vaccines.