MODULATION OF IMMUNE RESPONSES DURING PREGNANCY

怀孕与免疫功能的变化有关， 保护胎儿免受有害的母体免疫反应，但也 增加母亲对感染的易感性，并可能加剧或 减轻自身免疫性疾病。 本提案将使用 流感病毒A/PR/8/34血凝素（PR 8 HA）， 用于确定调节免疫的因素的模型抗原 小鼠妊娠期间对病毒、母体和胎儿抗原的反应。 以下具体问题将得到解决：（1）如何 妊娠相关的免疫功能变化调节母体免疫 对流感病毒的反应？ 抗病毒的具体方面 在怀孕期间受到抑制或增强的免疫力将 通过比较妊娠和非妊娠BALB/c小鼠的 产生流感病毒特异性免疫应答的能力。 如何 妊娠影响流感病毒特异性辅助性T细胞（Th）的能力 细胞分化成不同的表型（例如Th 1对Th 2 细胞）将使用表达以下蛋白的转基因（Tg）小鼠进行检查： HA特异性T细胞受体（TCR Tg小鼠）。2)怀孕会影响 对作为母体自身抗原的流感HA的自身反应性？是否 妊娠影响自身反应性HA特异性T细胞和/或 将在表达HA的小鼠中检查B细胞应答， 新自身抗原（HA Tg小鼠）。 此外，在多大程度上 在HA Tg小鼠中母体抗HA（自身）Th应答被抑制或 修饰（全身或子宫引流淋巴结） 怀孕期间将被确定。3)产妇如何免疫 系统将HA视为胎儿抗原？ 雌性BALB/c小鼠将 与雄性HA Tg小鼠交配，胎儿HA 激活或诱导母体中的抗原特异性耐受 将分析HA特异性T和/或B细胞。 表达式是否在 不同的胎儿细胞类型影响HA如何被胎儿细胞感知。 将评估母体免疫系统。 如何诱导 抗病毒免疫反应可能对胎儿发育有害， 也要评估。 通过定义母体免疫系统 系统容纳胎儿同种异体移植物，这些研究可以提供 在移植和自身免疫领域的临床益处。 确定妊娠对病毒和免疫应答的影响 自身抗原，以及母体免疫对胎儿的影响 发展，可能同样有利于妇女的健康和儿童的发展。

Pregnancy is associated with changes in immune function which may protect the fetus from harmful maternal immune responses, but which also increase maternal susceptibility to infections and can exacerbate or alleviate particular autoimmune diseases. This proposal will use the influenza virus A/PR/8/34 hemagglutinin (PR8 HA) as a well characterized model antigen with which to determine factors modulating the immune responses to viral, maternal and fetal antigens during murine pregnancy. The following specific questions will be addressed: 1) How do pregnancy-associated changes in immune function modulate maternal immune responses to influenza virus? The specific aspects of anti-viral immunity that are suppressed or enhanced during pregnancy will be determined by comparing pregnant and non-pregnant BALB/c mice for their abilities to generate influenza virus-specific immune responses. How pregnancy affects the capacity of influenza virus-specific T helper (Th) cells to differentiate into distinct phenotypes (e.g. Th1 versus Th2 cells) will be examined using transgenic (Tg) mice expressing HA-specific T cell receptors (TCR Tg mice). 2) Does pregnancy affect autoreactivity to influenza HA as a maternal self antigen? Whether pregnancy influences the magnitude of autoreactive HA-specific T and/or B cell responses will be examined in mice that express the HA as a neo-self antigen (HA Tg mice). In addition, the extent to which maternal anti-HA (self) Th responses in HA Tg mice are suppressed or modified (either systemically, or in lymph nodes draining the uterus) during pregnancy will be determined. 3) How does the maternal immune system perceive the HA as a fetal antigen? Female BALB/c mice will be mated with male HA Tg mice, and the ability of the fetal HA either to activate or to induce antigen-specific tolerance among maternal HA-specific T and/or B cells will be analyzed. Whether expression in different fetal cell types affects how the HA is perceived by the maternal immune system will be evaluated. How the induction of anti-viral immune responses can be harmful to fetal development will also be assessed. By defining mechanisms by which the maternal immune system accommodates the fetal allograft, these studies may provide clinical benefits in the areas of transplantation and autoimmunity. Determining the effects of pregnancy on immune responses to viral and self antigens, and the effects of maternal immunity on fetal development, may similarly benefit women's health and child development.