TH2 BIAS EFFECT ON MALARIAL IMMUNITY IN CAMEROON

描述：(改编自申请人摘要)：对疟原虫的免疫力 在流行地区生活的成年人中的恶性疟原虫涉及到 针对寄生虫不同发育阶段的细胞免疫和体液免疫机制。 如果这种平衡被改变，免疫个体就会同时受到这两种疾病的影响。 感染和疾病。为了回应这一RFA，调查人员试图 确定参与抵抗和/或的体液和细胞因素 敏感度。怀孕代表了一种自然干预， 正常免疫的人会变得易感，但免疫力是 在妊娠晚期或分娩后不久重新建立。近期 数据显示，在怀孕期间， 炎症型Th1应答及其向主要Th1细胞的转变 Th2--反应。细胞因子的这种转变很可能会改变体内的微妙平衡 孕妇是获得豁免权所必需的。因此，调查人员 建议在整个过程中跟踪抗疟疾免疫反应的变化 并将其与免疫状态的变化进行比较。这群人 假设Th1/Th2平衡变化最大的女性 疟疾造成的最严重后果。 新生儿是第二个年龄段的人，在这个年龄段，免疫力会因为相对 一小段时间。所有出生在高流行区的新生儿都患有 被动获得的抗疟疾抗体本质上相当于 他们的母亲。此外，母亲患有胎盘性疟疾的婴儿 也可能在子宫内暴露于疟疾抗原并产生T细胞 在Th2环境中。因此，对地方性疾病新生儿的纵向研究 区域允许人们检查抗体(Ab)的效应功能 世界上的疟疾 缺乏其他获得性免疫反应，以及 在没有CD4-CD8细胞的情况下，T细胞也被激活。 该小组选择了5个免疫学参数进行评估，其中 与保护相关的概率，包括：(1)CD8+T细胞 肝期抗原；(2)抗原特异性Th1/Th2 CD4+T细胞比率 对无性阶段抗原；(3)抗疟疾抗体，可定义的FINE 对子孢子相关表位的特异性(例如，亲和力) 裂殖子入侵；(4)具有高亲和力的抗体分离株优势 Fc受体(FCR)；以及(5)贫血作为潜在的病理标志。 将在雅温德市内进行平行的免疫学研究 那里的传播率很低，而在Ngali，一个全年传播率高的农村村庄 疟疾的传播。希望是其中之一或它们的组合 可识别的免疫反应将与易感性/耐药性相关 可用于预测地方病流行人群的免疫状态 人口。

DESCRIPTION: (adapted from applicant's abstract): Immunity to Plasmodium falciparum in adults living in endemic areas involves a fine-balance between cellular and humoral immune mechanisms to different stages of the parasite. If this balance is altered, immune individuals become susceptible to both infection and disease. In response to this RFA, the investigators seek to identify humoral and cellular factors involved in resistance and/or susceptibility. Pregnancy represents one natural intervention whereby individuals who are normally immune become susceptible, but immunity is re-established during the third trimester or soon after delivery. Recent data show that during pregnancy there is a down-regulation of inflammatory-type Th1 responses and an accompanying shift to a predominant Th2-response. This shift in cytokines may well alter the fine balance in pregnant women that is required for immunity. Thus, the investigators propose to follow changes in antimalarial immune responses throughout pregnancy and compare them with changes in immune status. This group hypothesizes that women with the greatest shift in Th1/Th2 balance will have the most severe consequences from malaria. Newborns are a second age group in which immunity is lost over a relatively short period of time. All neonates born in hyperendemic areas have passively acquired antimalarial antibodies essentially equivalent to that of their mothers. In addition, infants whose mothers have placental malaria may also be exposed to malarial antigens in utero and develop T cells primed in a Th2 environment. Thus, longitudinal studies in neonates in endemic areas allow one to examine the effector functions of antibodies (Ab) to malaria in the absence of other acquired immune responses, as well as the influence of CD4-primed T cells in the absence of primed-CD8 cells. This group has selected to evaluate 5 immunological parameters with a high probability of correlating with protection, including: (1) CD8+ T cells to liver-stage antigens; (2) ratio of antigen-specific Th1 and Th2 CD4+ T cells to asexual-stage antigens; (3) antimalarial Ab with definable fine specificities (e.g., avidities) to epitopes involved in sporozoite or merozoite invasion; (4) predominance of Ab isolates with high affinity for Fc-receptors (FcR); and (5) anemia as a potential marker for pathology. Parallel immunologic studies will be conducted within the city of Yaounde where transmission is low and in Ngali, a rural village with high year-round transmission of malaria. The hope is that one or a combination of these identifiable immune responses will correlate with susceptibility/resistance and can be used to predict the immune status of people in endemic populations.