MODULATION OF IMMUNE RESPONSES DURING PREGNANCY

怀孕与免疫功能的变化有关，这可能 保护胎儿免受有害的母体免疫反应，但这也 增加产妇对感染的易感性，并可能加剧或 缓解特定的自身免疫性疾病。此提案将使用 流感病毒A/PR/8/34血凝素(PR8 HA) 用来确定免疫调节因素的模型抗原 小鼠妊娠期间对病毒、母体和胎儿抗原的反应。 将解决以下具体问题：1)如何 妊娠相关免疫功能变化对母体免疫的调节作用 对流感病毒的反应？抗病毒的具体方面 在怀孕期间被抑制或增强的免疫力将是 通过比较怀孕和未怀孕的BALB/c小鼠的 产生流感病毒特异性免疫反应的能力。多么 妊娠对流感病毒特异性T辅助细胞(Th)功能的影响 细胞分化为不同的表型(例如Th1和Th2 细胞)将使用转基因(TG)小鼠进行检测 HA特异性T细胞受体(TCRTg小鼠)。2)怀孕会不会影响 作为母体自身抗原对流感HA的自身反应性？是否 妊娠影响自身反应性HA特异性T和/或的大小 B细胞反应将在表达HA的小鼠身上进行检测 新自身抗原(HA-Tg小鼠)。此外，在多大程度上 HATG小鼠母体抗HA(自身)Th反应被抑制或 改良的(系统性的，或引流子宫的淋巴结) 怀孕期间的情况将会确定。3)母体如何免疫 系统将HA视为胎儿抗原？雌性BALB/c小鼠将成为 与雄性HA TG小鼠交配，以及胎儿HA 激活或诱导母体抗原特异性耐受 将对HA特异的T和/或B细胞进行分析。中的表达式 不同的胎儿细胞类型影响HA如何被 将对孕妇的免疫系统进行评估。如何进行归纳 抗病毒免疫反应可能有害于胎儿发育意志 也要接受评估。通过定义母体免疫的机制 系统适应同种异体胎儿移植，这些研究可能提供 在移植和自身免疫领域的临床益处。 确定怀孕对病毒免疫应答的影响 自身抗原，以及母体免疫对胎儿的影响 发展，同样可能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.