IMMUNOLOGY OF NORMAL PREGNANCY
Section snippets
The Immune System and the Trophoblast
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The trophoblast expresses (1) a unique major histocompatibility complex (MHC) antigen, HLA-G, which is polymorphic,98 and (2) other class I antigens that orchestrate many immune functions, including immune suppression and production of growth-promoting cytokines. This result renders the placenta a privileged organ, resistant to immune damage by lymphocytes, cytotoxic antibodies, and antigen–antibody complexes in most circumstances.
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The trophoblast forms a physical barrier to most immune
PLACENTAL COMPARTMENT AND CELL TYPES
To understand the immunology of pregnancy requires familiarity with the structure of the placenta and its cell types (Fig. 3). There are many trophoblast cell types in the placenta that initiate immune homeostasis or immune pathology with the mother. The first is the syncytiotrophoblast. It develops from the cytotrophoblast (an earlier cell type) by aggregation of these cells and then fusion into a syncytium. The same process occurs when myoblasts fuse to form myoblastic syncytium in the
LYMPHOID CELL TYPES AND FUNCTIONS IN MATERNAL DECIDUA
The maternal lymphocytes present in the human decidua during the early weeks of pregnancy are composed of CD56+ NK cells (80%), CD3+ T cells (10%), and CD14+ macrophages (10%).73 These leukocytes accumulate in large numbers and density specifically in the decidua at the implantation site. Their roles are important in directing a TH-1 cytotoxic or a TH-2 suppressive and growth-promoting response toward the placenta.25
Alloantibody Production
Maternal anti-paternal alloantibody production during pregnancy is well documented. In healthy pregnancies, paternal antigen, maternal antipaternal antibody complexes, and maternal anti-paternal antibodies are detected in the maternal serum from the earliest stages of pregnancy onward.103 The maternal alloimmune response is against some but not all of the mismatched HLA antigens of the fetus. These alloantibodies appear to be modulated by soluble HLA antigens and anti-idiotypic antibodies.103
IMMUNOMODULATORY PROTEINS
TJ6 proteins have significant immunomodulatory roles in both pregnancy-induced tolerance as well as thymic tolerance.90, 97 TJ6 is normally expressed within the uterus. Its expression is far greater in the decidual lymph nodes draining the uterus during pregnancy. Anti-TJ6 binding antibody destroys early pregnancy in mice.104 TJ6 has a definite role in the maintenance of the fetal allograft. TJ6 is a protein whose membrane form is regularly expressed on the B lymphocytes of women during a
CONCLUSION
The following summarizes the immune response during normal pregnancy:
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HLA-G, a polymorphic paternal antigen, is present on the implanting trophoblast cell and presents non–self-antigens (terminal peptides) to the mother (hidden self) (see Fig. 1).78
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The non–self-terminal peptides of HLA-G serve as adhesion molecules for CD8 antigen on decidual granular leukocytes that have already migrated to the decidua.108 These CD3− CD8+ CD56+ NK cells are functionally more inert to produce TH-1 related
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Cited by (12)
Enhancement of peripheral blood CD56<sup>dim</sup> cell and NK cell cytotoxicity in women with recurrent spontaneous abortion or in vitro fertilization failure
2012, Journal of Reproductive ImmunologyCitation Excerpt :While some believe that immune system suppression is necessary for a successful pregnancy (Beer et al., 1996), and a decrease in the percentage distribution in lymphocytes in peripheral blood or in the uterus has been shown (Baczkowski and Kurzawa, 2007). Increased activity of NK cells has been suspected to be involved in rejection of the fetus by the prevention of the trophoblast invasion of the endometrium (Lunghi et al., 2007), while others disagree (Beer and Kwak, 1998). Natural killer cells are an abundant population of human lymphocyte in the decidual, and are therefore expected to play a physiological role during the implantation process (Kwak et al., 1995; Matsubayashi et al., 2005).
Assays for the diagnosis of recurrent spontaneous abortion of immune origin
1999, Clinical Immunology NewsletterAn In Vitro Coculture Model to Study Cytokine Profiles of Natural Killer Cells During Maternal Immune Cell-Trophoblast Interactions
2006, Journal of the Society for Gynecologic InvestigationRisk factors associated with a new pregnancy loss and perinatal outcomes in cases of recurrent miscarriage treated with lymphocyte immunotherapy
2015, Journal of Maternal-Fetal and Neonatal MedicineAlloantibodies against blood cells in nuliparous pregnant women before and after induced abortions
2008, Revista Cubana de Hematologia, Inmunologia y Hemoterapia
Address reprint requests to Joanne Y.H. Kwak, MD, Reproductive Medicine, Women's Health Center, Finch University of Health Sciences/, The Chicago Medical School North, 3333 Green Bay Road, Chicago, IL 60064
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Departments of Microbiology and Immunology and Obstetrics and Gynecology, Finch University of Health Sciences/The Chicago Medical School North, Chicago, Illinois