TRANSPLACENTAL PASSAGE OF HIV AND IMMUNOGLOBULIN

描述：(改编自作者的摘要。)报告的发病率 艾滋病毒从受感染的母亲在产前和围产期传播给 婴儿的比例从30%到50%不等。尽管有证据表明 艾滋病毒经胎盘转移可以发生在怀孕早期，准确的 母体艾滋病毒通过胎盘传播的机制尚不清楚。这个 人类胎盘“屏障”，胎儿衍生的器官，它是界面 在母体和胎儿血管系统之间，已被证明是可渗透的 对细胞和可溶性母体元素都有影响。经胎盘转移术 艾滋病毒几乎肯定发生在母婴血管界面，在那里 母体血液洗涤胎儿胎盘组织。胎盘细胞 构成小叶胎儿子叶的物质本身就容易感染艾滋病毒 由于它们位于母胎交界处而引起的感染 以及它们的细胞表面特性。此外，滋养层细胞表达 免疫球蛋白和表面CD4的Fc受体。Fc受体，功能 在通过胎盘将母体免疫球蛋白输送到胎儿的过程中， 也介导与母体抗HLV抗体复合的HIV的转移，或 导致携带Fc的胎盘细胞感染HIV的增强 感受器。应注意以下几点：(A)艾滋病毒的存在 抗原在携带Fc受体的Hofbauer细胞中呈CD4阳性 在艾滋病毒阳性孕妇的胎盘中显示；(B) 研究表明，不同类型的细胞可以改变HIV的趋向性，从而影响 病毒的细胞致病性；(C)艾滋病毒通过胎盘传播的影响 细胞尚不清楚，但它可能会影响HIV对胎儿细胞的趋向性 亚群；(D)在宫内感染的婴儿有较高的发病率 多器官系统受累以及免疫功能障碍； (E)分离的灌流人胎盘子叶(IPC)已被用作 一种研究可溶性代谢产物和药物经胎盘转运的模型 自1967年以来，最近被用于评估经胎盘转移术 齐多夫定(AZT)。因此，首席调查员提议使用 新奇调查中的IPC以描绘经胎盘 艾滋病毒、免疫球蛋白和艾滋病毒的传递：抗艾滋病毒免疫球蛋白复合体。她和 她的研究人员将：(1)确定 经胎盘转移游离病毒粒子和感染HIV的自体 孕妇白细胞的顺序，并将量化胎儿中的感染细胞 流通领域；(2)直接决定企业的相对效率 经胎盘通过确定的类别和亚类的免疫球蛋白， 从母体循环到胎儿循环；以及(3)定位 HIV：抗HIV-Ig G复合体在灌流胎盘中的沉积 小叶，探讨胎盘单核细胞的潜在增强作用 感染HIV：免疫球蛋白复合体，从而监测免疫复合体诱导 胎盘病理学。

DESCRIPTION: (Adapted from the author's abstract.) The reported incidence of pre- and perinatal transmission of HIV from an infected mother to the infant ranges from 30% to 50%. Although some evidence indicates that transplacental transfer of HIV can occur early in gestation, the precise mechanism by which maternal HIV transits the placenta is not known. The human placental "barrier," a fetally-derived organ which is the interface between maternal and fetal vascular systems, has been shown to be permeable to both cellular and soluble maternal elements. Transplacental transfer of HIV almost certainly occurs at the maternal-fetal vascular interface, where maternal blood bathes the fetal placental tissues. The placental cells that compose the lobular fetal cotyledons are themselves susceptible to HIV infection by virtue of both their location at the maternal-fetal interface and by their cell surface properties. Further, trophoblastic cells express Fc receptors for immunoglobulin and surface CD4. Fc receptors, functioning in transplacental transport of maternal immunoglobulin to the fetus, could also mediate transfer of HIV complexed with maternal anti-HlV IgG, or result in the enhancement of HIV infection of placental cells bearing Fc receptors. Certain observations should be noted: (a) the presence of HIV antigen in Fc receptor-bearing, CD4-positive Hofbauer cells has been demonstrated in the placenta in an HIV-positive pregnancy; (b) growth in different cell types has been shown to alter HIV tropism, thus influencing viral cytopathogenicity; (c) the effect of HIV passage through placental cells is not known but it may influence HIV tropism for fetal cell sub-populations; (d) infants infected in utero have a high incidence of multi-organ-system involvement as well as of immunologic dysfunction; and (e) the isolated perfused human placental cotyledon (IPC) has been used as a model to study transplacental transfer of soluble metabolites and drugs since 1967 and was used recently to evaluate transplacental transfer of zidovudine (AZT). Accordingly, the Principal Investigator proposes to use the IPC in novel investigations in order to delineate transplacental passage of HIV, immunoglobulins, and HIV:anti-HIV IgG complexes. She and her research associates will: (1) determine the efficiency of transplacental transfer of free virions and HIV-infected autologous maternal leukocytes in order and will quantify infected cells in the fetal circulation; (2) determine directly the relative efficiency of the transplacental passage of immunoglobulin of defined class and subclass, from the maternal circulation to the fetal circulation; and (3) localize the deposition of HIV:anti-HIV IgG complexes in the perfused placental lobule and investigate the potential enhancement of placental monocyte infection by HIV:IgG complexes, monitoring thereby immune complex-induced placental pathology.