Gurka G, Rocklin R E
JAMA. 1987 Nov 27;258(20):2983-7.
The maternal immune system is challenged with paternal antigens through exposure to trophoblast tissue and fetal cells crossing the placenta into the maternal circulation. The dose of antigen, the manner of presentation (cellular, subcellular, or soluble), and the nature of the antigen all determine the type of response that will be elicited. It is also clear that complex maternal immunologic responses, including antibodies to red blood cell antigens, HLA-A, HLA-B, HLA-C, and HLA-D antigens, and cell-mediated responses such as proliferation, lymphokines, cytotoxicity, and suppressor cells, are generated to a variety of paternal antigenic determinants. The fact that some of these reactions are detected in vitro in the absence of maternal serum, but not in its presence, suggests that the local milieu is important in influencing their expression in vivo. For example, such factors as hormones (cortisol, progesterone, and estrogen), pregnancy-associated glycoproteins (alpha 2-macroglobulin and beta 1-glycoprotein) and AFP, which have immunosuppressive properties, may all serve nonspecifically to inhibit and decrease the general tone of maternal immunologic responses, particularly at the placental interface, where many of these factors are present in high concentrations. However, these nonspecific factors may not be sufficient to prevent presensitized effector lymphocytes from continuing an ongoing rejection process, as is often the case in the chronic rejection of an allograft. For this purpose, specific enhancing antibodies would play an important role by blocking maternal responses or protecting the fetus. There may be a subtle balance created on the trophoblast cell surface between specific antibodies and trophoblast or embryonic alloantigens, resulting in limited expression of antigens capable of inducing rejection reactions. This could favor the production of blocking antibodies and/or T-suppressor cells, as opposed to cytotoxic antibody and killer cells. In fact, low levels of antigen density on the cell surface favor a blocking effect by IgG rather than cytotoxicity. Blocking or enhancing antibodies can exert their effect on maternal immunologic responses in several ways. They could block the afferent limb by combining with antigen and preventing sensitization or increasing the level of sensitivity. An example of the latter would be the coating of fetal cells that enter the maternal circulation. Enhancing antibodies could work directly on the effector cells to suppress their function. The antibody itself, or more likely antigen-antibody complexes, may be important in this regard.(ABSTRACT TRUNCATED AT 400 WORDS)
母体免疫系统会通过接触滋养层组织以及穿越胎盘进入母体循环的胎儿细胞，从而接触到父系抗原。抗原的剂量、呈现方式（细胞、亚细胞或可溶性）以及抗原的性质，都决定了将会引发的免疫反应类型。同样清楚的是，针对多种父系抗原决定簇会产生复杂的母体免疫反应，包括针对红细胞抗原、HLA - A、HLA - B、HLA - C和HLA - D抗原的抗体，以及细胞介导的反应，如增殖、淋巴因子、细胞毒性和抑制细胞。在体外，一些这类反应在没有母体血清时能被检测到，但在有母体血清时则检测不到，这表明局部环境对于影响它们在体内的表达很重要。例如，具有免疫抑制特性的激素（皮质醇、孕酮和雌激素）、妊娠相关糖蛋白（α2 - 巨球蛋白和β1 - 糖蛋白）以及甲胎蛋白等因素，都可能非特异性地抑制并降低母体免疫反应的总体强度，尤其是在胎盘界面，这些因素在那里大量存在。然而，这些非特异性因素可能不足以阻止预先致敏的效应淋巴细胞继续进行正在进行的排斥过程，就如同同种异体移植物慢性排斥中常见的情况那样。为此，特异性增强抗体通过阻断母体反应或保护胎儿发挥重要作用。在滋养层细胞表面，特异性抗体与滋养层或胚胎同种异体抗原之间可能形成一种微妙的平衡，导致能够诱导排斥反应的抗原表达受限。这可能有利于产生阻断抗体和/或T抑制细胞，而不是细胞毒性抗体和杀伤细胞。事实上，细胞表面低水平的抗原密度有利于IgG发挥阻断作用而非细胞毒性作用。阻断或增强抗体可通过多种方式对母体免疫反应产生影响。它们可以通过与抗原结合并防止致敏或提高敏感性水平来阻断传入环节。后者的一个例子是进入母体循环的胎儿细胞的包被。增强抗体可直接作用于效应细胞以抑制其功能。抗体本身，或者更有可能是抗原 - 抗体复合物，在这方面可能很重要。（摘要截选至400字）
