人类免疫缺陷病毒母-胎垂直传播研究进展

携带人类免疫缺陷病毒1型(human immunodeficiency virus type 1,HIV-1)的儿童中有80％-90％是因垂直传播而感染病毒。较之成人,儿童感染HIV-1后疾病进程更快、死亡率更高。未经干预的HIV-1阳性孕妇有13％-48％发生HIV-1病毒垂直传播,而经抗病毒药物,如齐多夫定(zidovudine,AZT)治疗后,垂直传播率可降至8％左右。     

NKT细胞在母胎免疫调节中的作用

NKT细胞是继T、B、NK细胞之后发现的第4类淋巴细胞,是联系固有免疫和获得性免疫间的桥梁,通过分泌不同的细胞因子以维持Th1/Th2平衡。目前研究显示,除了α-Galcer以外,还有许多的自然配体及病原相关配体影响NKT细胞的免疫活动。NKT细胞通过分泌不同的细胞因子,调节机体的免疫平衡,也是影响母-胎容受及维持正常妊娠的一个重要成员。推测NKT细胞及NK西北在妊娠维持中可能较T细胞起到更重要的作用,妊娠期疾病如妊娠期肝内胆汁淤积症、子痫前期均与NKT细胞异常有关。对NKT细胞的进一步研究,将有助于提高对妊娠期疾病的认识及诊治水平。     

TCRγδT淋巴细胞和母胎免疫调节的关系

妊娠是一复杂的生理过程，妊娠早期母胎界面的免疫反应状态决定妊娠结局。TCRγδT淋巴细胞具有识别绒毛滋养细胞表达的人类白细胞抗原G和E，并通过某种机制调节Th1／Th2型细胞因子的平衡偏移及免疫效应细胞活性等作用，而这些因素是参与母胎界面免疫反应的关键环节，认为TCRγδT淋巴细胞在妊娠早期的母胎免疫调节中发挥重要作用。     

HLA-G在母胎界面中的免疫调节作用

人类白细胞G抗原(HLA-G)是特异性表达在母胎界面上的一种蛋白，其在母胎免疫耐受及维持正常妊娠中起重要作用，近年来引起国内外学者的广泛重视。本文概述HLA-C在母胎界面中的免疫调节作用及与妊娠疾病的关系。     

母胎界面免疫调节与子痫前期关系的研究进展

子痫前期是妊娠期特发性疾病,可累及全身各器官系统,严重威胁母儿健康,患者远期罹患心血管疾病、肾脏疾病等风险也显著增加,但病因及发病机制尚不明确,因而目前尚无有效的防治措施。现已明确,母胎界面免疫活性细胞及免疫分子的相互作用、免疫调节机制的异常可直接导致滋养细胞的浅着床、螺旋动脉重铸障碍,从而在子痫前期的发病机制中起着重要作用。     

母-胎肠道内微生物群落以及母-胎微生物传输的研究进展

妊娠胎盘、羊水、足月及早产儿胎便中均存在小型、多样性较低的微生物群落。研究表明这些肠道微生物群落组成与母体肠道、口腔微生物群落最为相似,而且母体肠道微生物群落发生改变会引起胎儿肠道微生物群落的改变,猜测肠道微生物的定植很可能发生在妊娠期,并且可能存在母-胎之间微生物的传输通路。本研究就胎儿肠道微生物群落的发现及其国内外研究进展作一综述。     

母胎界面免疫微环境的研究进展

母胎界面是母体组织与胎儿成分直接接触的界面，其局部的免疫应答在妊娠的建立、维持以及临产的发动中均发挥关键作用。母胎界面免疫微环境由蜕膜中的免疫细胞及其分泌的细胞因子组成，在妊娠期类固醇激素等因素的影响下，蜕膜组织中淋巴细胞的亚群及其分泌的细胞因子均发生一系列的生理变化．构成母胎界面局部独特的、动态的免疫微环境。综述近年有关妊娠母胎界面的免疫微环境的研究进展。     

自发性早产母胎界面子宫自然杀伤细胞亚群及T淋巴细胞亚群变化的研究

目的:研究不明原因早产发生时,母胎界面中自然杀伤细胞亚群及T淋巴细胞亚群的变化,探讨早产发生机制.方法:采用流式细胞技术,分别检测足月妊娠分娩孕妇30例(正常妊娠组)和不明原因孕周满28周至不满37周无医学指针终止妊娠的孕妇30例(早产组)母胎界面底蜕膜组织中CD4+T细胞、CD8+T细胞、CD56+CD16+NK细胞百分比、Th1及Th2细胞的百分比.结果:①早产组患者CD4+T细胞、CD56+CD16+NK细胞百分比明显高于正常妊娠组(P<0.05),CD8+T细胞百分比明显低于正常妊娠组(P<0.05);②早产组Th1细胞、Th1/Th2比例明显高于正常妊娠组(P<0.01).结论:母胎界面局部T淋巴细胞亚群、子宫自然杀伤细胞百分比的改变及Th11细胞增多与不明原因自发性早产相关.     

母胎界面免疫微环境的研究进展

母胎界面是母体组织与胎儿成分直接接触的界面,其局部的免疫应答在妊娠的建立、维持以及临产的发动中均发挥关键作用.母胎界面免疫微环境由蜕膜中的免疫细胞及其分泌的细胞因子组成,在妊娠期类固醇激素等因素的影响下,蜕膜组织中淋巴细胞的亚群及其分泌的细胞因子均发生一系列的生理变化,构成母胎界面局部独特的、动态的免疫微环境.综述近年有关妊娠母胎界面的免疫微环境的研究进展.     

免疫抑制因子MNSFβ在母-胎界面作用机制的研究进展

母-胎界面免疫耐受状态的形成是胚胎植入和妊娠维持过程中的一个关键环节,唯其机制尚不十分清楚。单克隆非特异性抑制因子-β(MNSFβ)(Fau)是一种在体内广泛分布的非抗原特异性的免疫抑制因子,能抑制激活型T细胞和B细胞的增殖,以及T细胞和巨噬细胞中TNFα等细胞因子的表达,并在胚胎植入及妊娠维持过程中发挥重要作用。由文献报道推测:MNSFβ蛋白有分泌型和非分泌型2种表达形式,而且前者是以完整的MNSFβ蛋白分子单体或多聚体形式分泌到细胞外,后者以MNSFβ蛋白的Ubi-L肽段分别与Bcl-G或endophilin II形成复合物的形式存在于细胞质中。MNSFβ对蜕膜巨噬细胞(dMac)中Cox-2和p53表达的抑制是不利于胚胎植入和妊娠维持的。     

Potentiating maternal immune tolerance in pregnancy: A new challenging role for regulatory T cells

The maternal immune system needs to adapt to tolerate the semi-allogeneic conceptus. Since maternal allo-reactive lymphocytes are not fully depleted, other local/systemic mechanisms play a key role in altering the immune response. The Th1/Th2 cytokine balance is not essential for a pregnancy to be normal. The immune cells, CD4+CD25+Foxp3+, also known as regulatory T cells (Tregs), step in to regulate the allo-reactive Th1 cells. In this review we discuss the role of Tregs in foeto-maternal immune tolerance and in recurrent miscarriage as well as their potential use as a new target for infertility treatment. Animal and human experiments showed Treg cell number and/or function to be diminished in miscarriages. Murine miscarriage can be prevented by transferring Tregs from normal pregnant mice. Tregs at the maternal–fetal interface prevented fetal allo-rejection by creating a “tolerant” microenvironment characterised by the expression of IL-10, TGF-β and haem oxygenase isoform 1 (HO-1) rather than by lowering Th1 cytokines. Tregs increase placental HO-1. In turn, HO-1 may lead to up-regulation of TGF-β, IL-10 and CTLA-4. In vivo experiments showed Tregs sensitisation from paternal antigens to be essential for maternal–fetal tolerance. Tregs increase throughout pregnancy and diminish in late puerperium. Recent data also support the capacity of Tregs to block maternal effector T cells, thereby reducing the maternal–fetal pathological responses to paternal antigens. These findings also permit us to consider new strategies for improving pregnancy outcomes, i.e., anti-TNF blockers and granulocyte-colony stimulating factors as well as novel approaches to therapeutically exploiting Treg + cell memory.     

The changing maternal "self" hypothesis: a mechanism for maternal tolerance of the fetus

Recent advances in placental biology and immunology lead us to propose a novel hypothesis for maternal tolerance of the semi-allogeneic fetus and amelioration of rheumatoid arthritis (RA) during pregnancy. The initial event in this hypothesis is extrusion of placental apoptotic syncytiotrophoblast debris recently identified to contain intracellular fetal HLA Class II molecules, into maternal blood. The second event is uptake of apoptotic syncytiotrophoblast by immature maternal dendritic cells and presentation of fetal HLA class II peptides. In addition to presenting foreign antigens, HLA molecules also present HLA self-peptides. In the setting of the non-inflammatory environment of pregnancy, this process is expected to induce peripheral tolerance of fetal antigens through T cell death, anergy or induction of regulatory T cells in the lymph nodes. This hypothesis suggests a mechanism by which the simultaneous presentation of fetal and self (RA-associated) HLA peptides by tolerogenic dendritic cells during pregnancy may explain the observed amelioration of RA as a secondary benefit of fetal tolerance. After delivery, apoptotic syncytiotrophoblast debris disappears from maternal blood, autoimmunity returns and RA recurs. Thus, during pregnancy maternal immunologic "self" includes fetal HLA Class II as a result of apoptotic syncytiotrophoblast uptake by maternal tolerogenic dendritic cells.     

Tryptophan catabolism prevents maternal T cells from activating lethal anti-fetal immune responses

The murine conceptus is protected from maternal immunity by cells expressing indoleamine dioxygenase (IDO), which catabolizes tryptophan. Induction of lethal maternal anti-fetal immunity requires effective pharmacologic inhibition of IDO enzyme activity and the presence of maternal T cells, but not B cells and also depends on the degree of maternal-fetal tissue incompatibility. Based on these findings, we propose a model to explain the role of IDO in suppressing maternal immunity and the mechanism of fetal allograft rejection, when IDO activity is inhibited during gestation. This model incorporates observations that fetal allograft rejection is T cell dependent, antibody-independent and is accompanied by a novel type of inflammation involving extensive complement deposition at the maternal-fetal interface, when IDO activity is blocked during murine pregnancy.     

Is maternal alkalosis harmful to the fetus?

Normal pregnancy is characterized by a compensated respiratory alkalosis. The effect of maternal alkalosis on the fetus is less well understood than the more common problem of maternal acidosis. We present a case of maternal alkalosis, complicated by bronchial asthma, in which the fetus was stillborn. The pathophysiology of this condition is discussed with data to support the potential harm of maternal alkalosis in pregnancies complicated by a fetus with borderline reserve. In such instances, the fetus should be carefully monitored and consideration might be given to therapy such as the use of acetozolomide, discouraging hyperventilation by the mother and even early delivery of the fetus.     

Identification of maternal hematopoietic cells in a 2nd-trimester fetus

OBJECTIVE: To study the subset of maternal cells in fetal tissue in a 2nd-trimester fetus with malformations. METHODS: By cell sorting and PCR amplification, we studied the presence of maternal CD3+ (T cells), CD19+ (B cells), CD34+ (hematopoietic progenitor cells), and CD45+ (leukocytes) in different tissues in a 2nd trimester fetus. RESULTS: Maternal cells could be detected in fetal liver, lung, heart, thymus, spleen, adrenal gland, kidney, and placenta, but not in pancreas or gonadal tissue. In thymus, liver, and spleen, cell separation showed CD3+, CD19+, CD34+, and CD45+ positive cells of maternal origin. CONCLUSIONS: The present study indicates that maternal cells are widely distributed in a 2nd-trimester fetus. In addition, we found subpopulations of maternal cells belonging to lymphoid and myeloid lineages and hematopoietic progenitors with engraftment capacity in liver, spleen, and thymus. The study warrants further investigations on presence and possible biological function of maternal cells in normal and malformed fetuses.     

Partition of maternal nutrients to the placenta and fetus in the sheep

Utilizing the Fick Principle, the fluxes of oxygen and glucose leaving the uterine circulation and entering the fetal umbilical circulation were measured simultaneously in 35 chronically catheterized sheep. Additionally, the distribution of placentally produced lactate into the uterine and umbilical circulations was measured by the same techniques. Under unstressed conditions, placental oxygen consumption accounted for approximately half the oxygen exiting the uterine circulation. Placental glucose consumption averaged 75% of the glucose exiting the uterine circulation, and this proportion increased with decreasing glucose concentration in the maternal artery. Lactate was produced at a high rate by all placentae, and distributed disproportionately to the fetus, in spite of higher fetal lactate concentration.Fetal metabolism was aerobic, as demonstrated by a high rate of net oxygen consumption and a high rate of net lactate consumption. Fetal oxygen metabolism correlated well with fetal weight and with the sum of net fetal lactate and glucose consumption.     

Immunological tolerance of the human fetus

Why is the fetus not rejected as foreign tissue? The maternal and fetal immune systems temporarily coexist; both are precisely tuned to detect and reject foreign invasion and yet somehow achieve a symbiotic relationship. This mutual state of tolerance is obviously critical for carrying pregnancy to full term. Two active arms of the immune system maintain protection of the host: the first of these involves a humoral immune system in which foreign tissue invokes an antibody response by recognition of antigenic surfaces by the B-cell, the second arm involves cell-mediated immunity in which T-cells and natural killer (NK) cells seek out and destroy foreign tissue. Several mechanisms are thought to invoke the immune tolerance of the fetus. These include: absence of major histocompatibility complex (MHC)-I antigens, presence of unique human lymphocyte antigen (HLA) surface molecules, nonspecific reduction of systemic immunoreactivity, possible role of blocking antibody, expressions of complement regulatory proteins, and factors of locally reduced immunoreactivity. Ultimately, developing regimens to control these elements in the clinical setting may help us overcome preterm labor, infertility, and preeclampsia. Available evidence regarding immune tolerance of the human fetus, integrated into a workable model, and focused at an overview level are systematically reviewed in this article.     

The route of maternal IgM transport to the rabbit fetus.

The route of IgM transport to the rabbit fetus was investigated by comparing its localization with that of IgG in the yolk sac splanchnopleure and uterine tissues using direct immunofluorescence and immunodiffusion analysis. IgM was first detected in fetal serum at 20 days of gestation but was present in uterine fluid at 18 days, the earliest stage tissues and fluids were examined. IgM was co-localized with IgG in the yolk sac endoderm basement membrane and in the vascular mesenchyme of the yolk sac splanchnopleure providing evidence of its transport to fetal blood; it was also present in vesicles in the yolk sac endoderm. IgM could not be detected in uterine fluid of nonpregnant uterine horns of rabbits unilaterally pregnant. Human IgM injected into the maternal circulation was readily transported to the uterine fluid and across the yolk sac splanchnopleure to fetal blood indicating that IgM secreting plasma cells, found to be present in the uterine stroma, contributed little towards IgM in the uterine fluid. Degenerating paraplacental decidual tissue, a feature of rabbit pregnancy, is suggested to be a major route for maternal immunoglobulin transport to the uterine fluid.