Immunological Tolerance of the Human Fetus

Abstract

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.

Human Embryonic Stem Cells Possess Immune‐Privileged Properties

“…The immunologically privileged state of the human embryo has been attributed to a unique relationship between the maternal host and fetal tissue that is dependent on the physiology and structure of the placenta [4,[6][7][8][9]. Based on our current observations using hESCs as a model, the lack of maternal immunogenic response to the human embryo may be independent of complex in vivo interactions mediated by the placental barrier [5] but instead is due to unique properties of embryonic human cells that inhibit local immune responses to the fetus.…”

“…One exception to this rule is maternal tolerance to the fetal conceptus expressing paternal antigens [4,5]. In spite of our growing understanding of the immune system, the mechanism of immune privilege exhibited by fetal tissue remains unknown [4,[6][7][8][9]. Accordingly, it is reasonable to assume that immune responses to human embryonic cells may reveal unanticipated results, and therefore must be examined experimentally.…”

Identifying Insomnia in Early Pregnancy: Validation of the Insomnia Symptoms Questionnaire (ISQ) in Pregnant Women

“…We contend that a substantial number of women are at risk of developing insomnia in early pregnancy based on the myriad physiological and psychological changes that occur. The fi rst weeks of conception are characterized by marked fl uctuations in immune and endocrine markers [22][23][24][25][26] known to directly and indirectly affect sleep. Physical symptoms, such as increased need to urinate, backache, and nausea, are recognized disruptors of sleep.…”

Colony-Stimulating Factor-1-Dependent Macrophage Functions Regulate the Maternal Decidua Immune Responses againstListeria monocytogenesInfections during Early Gestation in Mice

“…On the other hand, pregnancy also presents a major challenge to the maternal immune system, due to the existence of paternal alloantigens in the fetus that are foreign to the mother. Thus, strict regulation of the maternal immune system during pregnancy to induce immune tolerance of the developing fetus is crucial to a successful pregnancy (21), and an immunosuppressive environment at the maternofetal interface has been suggested (40). Nevertheless, the immune system of the pregnant mother has to balance the need to provide protection against microbial infections without compromising the viability of the allogeneic fetus.…”