Placental Immune Defences – Protection against Rejection and Infection

Abstract

The placenta is well recognised for its role as the gateway for provision of nutrients to and removal of waste products from the foetus. The placenta also needs to protect the foetus from maternal immunological attack and provide it with rudimentary immune defence mechanisms through the passage of maternally derived immunoglobulin G in particular. There are multiple cellular and soluble mechanisms that have evolved to prevent rejection of the foetal semi‐allograft by the mother's immune system. These mechanisms also contribute to key physiological processes within the placenta, mother and foetus to ensure pregnancy success. Poor development of the placenta is associated with adverse pregnancy outcomes such as miscarriage and preeclampsia. The placenta is also recognised increasingly for its role in determining longer‐term health of the offspring.

Key Concepts

  • Placental development is tightly regulated and leads to a highly structured organ that supports the growth and development of the foetus.
  • Numerous cellular and soluble mechanisms control the maternal immune response to the foetal semi‐allograft.
  • The placenta enables immune defence of the immunologically immature foetus that persists for some months after the baby is born.
  • Perturbations of placental development are associated with early pregnancy loss or later adverse pregnancy outcomes.
  • The placenta is central to the developmental origins of health and disease that determine lifelong health of the offspring.

Keywords: placenta; trophoblast; pregnancy; foetus; immunoglobulin; cytokine; innate immunity

Figure 1. Schematic picture of the attachment (a) and implantation of the blastocyst (b). Liljander et al. . Reproduced with permission of John Wiley and Sons.
Figure 2. Schematic drawing of the human placenta and organisation of the foetal membranes. The tree‐like structure of the villi constitutes the part of the placenta where maternofoetal exchange of nutrients and waste occurs. The yolk sac can be observed between the amnion and the chorion in early pregnancy. By the end of the third month, the amnion and chorion have fused. Liljander et al. . Reproduced with permission of John Wiley and Sons.
close

References

Aghaeepour N, Ganio EA, Mcilwain D, et al. (2017) An immune clock of human pregnancy. Science Immunology 2: eaan2946. DOI: 10.1126/sciimmunol.aan2946.

Barker DJP (2007) The origins of the developmental origins theory. Journal of Internal Medicine 261: 412–417. DOI: 10.1111/j.1365‐2796.2007.01809.x.

Burton GJ and Jauniaux E (2015) What is the placenta? American Journal of Obstetrics and Gynecology 213: S6.e1–S6.e4. DOI: 10.1016/j.ajog.2015.07.050.

Chamley LW, Holland OJ, Chen Q, et al. (2014) Review: where is the maternofetal interface? Placenta 35: 74–80. DOI: 10.1016/j.placenta.2013.10.014.

Conrad ML, Ferstl R, Teich R, et al. (2009) Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. The Journal of Experimental Medicine. DOI: 10.1084/jem.20090845.

Fu B, Zhou Y, Ni X, et al. (2017) Natural killer cells promote fetal development through the secretion of growth‐promoting factors. Immunity 47: 1100–1113.e6. DOI: 10.1016/j.immuni.2017.11.018.

Gamliel M, Goldman‐Wohl D, Isaacson B, et al. (2018) Trained memory of human uterine NK cells enhances their function in subsequent pregnancies. Immunity 48: 951–962.e5. DOI: 10.1016/j.immuni.2018.03.030.

Girardi G, Bulla R, Salmon JE and Tedesco F (2006) The complement system in the pathophysiology of pregnancy. Molecular Immunology. DOI: 10.1016/j.molimm.2005.06.017.

Gomez‐Arango LF, Barrett HL, McIntyre HD, et al. (2017) Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant Women. Scientific Reports 7: 1–10. DOI: 10.1038/s41598‐017‐03066‐4.

Gomez de Agüero M, Ganal‐Vonarburg SC, Fuhrer T, et al. (2016) The maternal microbiota drives early postnatal innate immune development. Science 351: 1296–1302. DOI: 10.1126/science.aad2571.

Guttmacher AE, Maddox YT and Spong CY (2014) The human placenta project: placental structure, development, and function in real time. Placenta 35: 303–304. DOI: 10.1016/j.placenta.2014.02.012.

Jennewein MF, Abu‐Raya B, Jiang Y, Alter G and Marchant A (2017) Transfer of maternal immunity and programming of the newborn immune system. Seminars in Immunopathology 39: 605–613. DOI: 10.1007/s00281‐017‐0653‐x.

Kinder JM, Jiang TT, Ertelt JM, et al. (2015) Cross‐generational reproductive fitness enforced by microchimeric maternal cells. Cell 162: 505–515. DOI: 10.1016/j.cell.2015.07.006.

Lapaire O, Holzgreve W, Oosterwijk JC, Brinkhaus R and Bianchi DW (2007) Georg Schmorl on trophoblasts in the maternal circulation. Placenta. DOI: 10.1016/j.placenta.2006.02.004.

Liljander M, Arvola M and Mattsson R (2007) Placental immune defences – protection against rejection and infection. In: eLS. DOI: 10.1002/9780470015902.a0001438.pub2.

Monsivais D, Matzuk MM and Pangas SA (2017) The TGF‐β family in the reproductive tract. Cold Spring Harbor Perspectives in Biology 9. DOI: 10.1101/cshperspect.a022251.

Munn DH, Zhou M, Attwood JT, et al. (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. DOI: 10.1126/science.281.5380.1191.

Nair S and Salomon C (2018) Extracellular vesicles and their immunomodulatory functions in pregnancy. Seminars in Immunopathology: 1–13. DOI: 10.1007/s00281‐018‐0680‐2.

O'Donoghue K, Chan J, De La Fuente J, et al. (2004) Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem‐cell trafficking in pregnancy. Lancet: 16631–16632. DOI: 10.1016/S0140‐6736(04.

PrabhuDas M, Bonney E, Caron K, et al. (2015) Immune mechanisms at the maternal‐fetal interface: perspectives and challenges. Nature Immunology. DOI: 10.1038/ni.3131.

Prescott SL (2013) Early‐life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases. Journal of Allergy and Clinical Immunology 131: 23–30. DOI: 10.1016/j.jaci.2012.11.019.

Regal JF, Gilbert JS and Burwick RM (2015) The complement system and adverse pregnancy outcomes. Molecular Immunology. DOI: 10.1016/j.molimm.2015.02.030.

Robertson SA, Care AS and Moldenhauer LM (2018) Regulatory T cells in embryo implantation and the immune response to pregnancy. Journal of Clinical Investigation 128: 4224–4235. DOI: 10.1172/JCI122182.

Romero R, Dey SK and Fisher SJ (2014) Preterm labor: one syndrome, many causes. Science 345: 760–765. DOI: 10.1126/science.1251816.

Ross KMK, Miller G, Culhane J, et al. (2016) Patterns of peripheral cytokine expression during pregnancy in two cohorts and associations with inflammatory markers in cord blood. American Journal of Reproductive Immunology 76: 406–414. DOI: 10.1111/aji.12563.

Tang MX, Hu XH, Liu ZZ, Kwak‐Kim J and Liao AH (2015) what are the roles of macrophages and monocytes in human pregnancy? Journal of Reproductive Immunology 112: 73–80. DOI: 10.1016/j.jri.2015.08.001.

Tessier DR, Yockell‐Lelièvre J and Gruslin A (2015) Uterine spiral artery remodeling: the role of uterine natural killer cells and extravillous trophoblasts in normal and high‐risk human pregnancies. American Journal of Reproductive Immunology 74: 1–11. DOI: 10.1111/aji.12345.

Thornburg KL and Marshall N (2015) The placenta is the center of the chronic disease universe. American Journal of Obstetrics and Gynecology 213: S14–S20. DOI: 10.1016/j.ajog.2015.08.030.

Trowsdale J and Betz AG (2006) Mother's little helpers: mechanisms of maternal‐fetal tolerance. Nature Immunology. DOI: 10.1038/ni1317.

Yockey LJ and Iwasaki A (2018) Interferons and proinflammatory cytokines in pregnancy and fetal development. Immunity 49: 397–412. DOI: 10.1016/j.immuni.2018.07.017.

Further Reading

Chang RQ, Li DJ and Li MQ (2018) The role of indoleamine‐2,3‐dioxygenase in normal and pathological pregnancies. American Journal of Reproductive Immunology 79. DOI: 10.1111/aji.12786.

Deshpande SS and Balasinor NH (2018) Placental defects: an epigenetic perspective. Reproductive Sciences 25: 1143–1160. DOI: 10.1177/1933719118766265.

Fleming TP (2018) The remarkable legacy of a father's diet on the health of his offspring. Proceedings of the National Academy of Sciences 115: 9827–9829. DOI: 10.1073/pnas.1813731115.

Fleming TP, Watkins AJ, Velazquez MA, et al. (2018) Origins of lifetime health around the time of conception: causes and consequences. The Lancet 391. DOI: 10.1016/S0140‐6736(18)30312‐X.

Heerema‐McKenney A (2018) Defense and infection of the human placenta. APMIS 126: 570–588. DOI: 10.1111/apm.12847.

Schumacher A and Zenclussen AC (2014) Regulatory T cells: regulators of life. American Journal of Reproductive Immunology 72: 158–170. DOI: 10.1111/aji.12238.

Singer JR and Weaver CT (2015) Daughter's tolerance of mom matters in mate choice. Cell 162: 467–469. DOI: 10.1016/j.cell.2015.07.030.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Thornton, Catherine A(Jun 2019) Placental Immune Defences – Protection against Rejection and Infection. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001438.pub3]