Immunologic Regulation in Pregnancy: From Mechanism to Therapeutic Strategy for Immunomodulation

Abstract

The immunologic interaction between the fetus and the mother is a paradoxical communication that is regulated by fetal antigen presentation and/or by recognition of and reaction to these antigens by the maternal immune system. There have been significant advances in understanding of abnormalities in the maternal-fetal immunologic relationship in the placental bed that can lead to pregnancy disorders. Moreover, immunologic recognition of pregnancy is vital for the maintenance of gestation, and inadequate recognition of fetal antigens may cause abortion. In this paper, we illustrate the complex immunologic aspects of human reproduction in terms of the role of human leukocyte antigen (HLA), immune cells, cytokines and chemokines, and the balance of immunity in pregnancy. In addition, we review the immunologic processes of human reproduction and the current immunologic therapeutic strategies for pathological disorders of pregnancy.

Bullous Dermatoses in Pregnancy

“…The mobile, extravillous fetal cytotrophoblast cells of the fetal-placenta unit contact with the maternal tissues and also with the maternal immune cells; they invade the placental matrix and endothelium and meet the maternal dendritic macrophages, NK cells, and T cells [2,3]. The classical allogeneic rejection of the fetal cells is avoided mostly because these cytotrophoblasts are MHC class II negative.…”

“…The classical allogeneic rejection of the fetal cells is avoided mostly because these cytotrophoblasts are MHC class II negative. Further immunological factors support the fetal tolerance at the maternal-fetal interface, such as the presence of complement inhibitory receptors, absence of major MHC expression together with expression of nonpolymorphic nonclassical presenting molecules on the extravillous fetal cytotrophoblasts in an unusual combination (HLA-G, HLA C, HLA-E) [4], as well as a special cytokine balance [3].…”

“…This is thought to be due to a temporary imbalance that develops between the differential cytokine secretion profiles and due to the preferentially Th1 or Th2 mediated immune responses in pregnancy preventing the rejection of the fetus. During the early phase of pregnancy, successful implantation occurs under a dominating Th1-type response in a proinflammatory microenvironment, whereas later the immunomodulation is shifted to a Th2 dominance to control endocrine and immune interactions in the advanced pregnancy [3].…”

Characteristics of immune cell changes before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion

“…An embryo that expresses paternal antigens may be considered a semi-allograft to the mother. Successful pregnancy depends on the immunologic status of the woman and her immunoregulatory compatibility with the embryo (Aluvihare et al, 2005;Guleria and Sayegh, 2007;Chen et al, 2012).…”

Increased maternal cytokine production and congenital heart defects

“…This dynamic maternal immunoregulation is complex and appears to involve multiple pathways (Chen et al, 2012). One important mechanism involves the regulation of T cell cytokines involved in cellular immunity, which includes the suppression of T helper (Th)1 cells that produce cytokines, IL-17, IL-2 and IFN-␥, and upregulation of Th2 cells, which produce IL-4, IL-5, IL-13, and IL-10 (Wegmann et al, 1993).…”