What Is Maternal Immune Tolerance?
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Maternal Immune Tolerance - Placental Health and Miscarriage

Published on Feb 01, 2023 and last reviewed on Jun 26, 2023   -  5 min read


The immune tolerance shown by a pregnant woman towards the fetus and placenta is known as maternal immune tolerance. Read the article to know more.


Pregnancy is a natural process that poses an immunological challenge because the body must accept the fetus. Maternal immune tolerance counters the immune response that could result in the rejection of the fetus, as the body considers it foreign. During the pregnancy period, the fetus inherits maternal and paternal antigens. For a successful pregnancy, the fetus is tolerated and nurtured, enjoying immune privileges that minimize the risk of being rejected by the maternal immune system. Multiple mechanisms contribute to tolerating the fetus, and the maternal immune system actively collaborates to maintain the immune balance and maternal-fetal tolerance.

What Happens In Maternal Immunity Tolerance?

Pregnancy is a unique condition where the maternal immune system continuously adapts to the stages of fetal development and signals from the environment. Some features can explain what happens:

  • The placenta is a key mediator of the fetal interaction that provides signals regulating the function of the maternal immune system and provides protective mechanisms to prevent the fetus from exposure to danger signals.

  • During pregnancy, the bacterial or viral infection induces a unique immunological response by the placenta. Type one interferon is one of the crucial signals providing pathways in the trophoblast cells.

  • Some useful mechanisms and physiological functions maintain the homeostasis of pregnancy and provide the placenta with adequate awareness to respond to infections.

  • Any disruption or disturbance in the type one interferon signaling in the placenta will lead to pregnancy complications and compromise fetal development.

  • The important role of placenta-derived type one interferon is focused much, which is responsible for regulating maternal immune homeostasis and protecting against viral infection.

  • This approach provides a new perspective on understanding placental immunological functions and protects the mother and fetus during infections.

What Are the Conditions in Which There Is Reduced Maternal Immune Tolerance?

The conditions in which there is reduced immune tolerance in pregnancy are:

  • Rh Disease: It is a condition when the mother produces antibodies against the Rhesus D antigen against her baby's red blood cells. It occurs if the mother is Rh-negative and the baby is Rh-positive. A small amount of Rh-positive blood from one of the previous pregnancies can enter the mother's circulation to make her produce IgG antibodies against the D antigen. Maternal antibodies can pass through the placenta into the fetus. If it is sufficient, it will destroy red blood cells leading to the development of the anti-Rh type hemolytic disease of the fetus and newborn.

  • Pre-Eclampsia: It is an abnormal immune response toward the placenta. In preeclamptic pregnant women, an increased inflammatory response at the maternal-fetal interface results in an infarct of the placenta. This can predispose to pre-eclampsia.

  • Pregnancies That Result From Egg Donation: They are associated with a greater risk of pregnancy-induced hypertension and placental pathology. This occurs due to a major genetic difference between the carrier and the biological mother. It has been studied that a higher incidence of certain conditions after egg donation is due to a reduced immune tolerance by the mother.

  • Recurrent Spontaneous Abortion (RSA): Recurrent spontaneous abortion is three or more miscarriages. It can occur due to various factors like anatomical, endocrine, or immune dysfunction at the maternal level.

  • Endometriosis: Endometriosis is the implantation of endometrial tissues outside the uterus. It can occur due to an alteration in the immune mechanism that results in implantation and proliferation of the tissue at an ectopic site.

  • Advanced Maternal Age: An advanced maternal age disrupts the T-cells at the maternal-fetal interface. This poses a risk of reduced fetal survival or an intrauterine growth restriction.

  • Viral Pathogenesis: There is a shift in immunity during pregnancy due to the suppression of cell-mediated immunity. This increases the risks of abortion, low birth weight, prematurity, and neurological benefits in the fetus.

What Does the Placenta Do?

The placenta nourishes the fetus during pregnancy. It develops in the uterus. Its function is to provide oxygen and nutrients to the developing baby. It also removes waste products from the baby's blood. It is attached to the uterus wall, and the baby's umbilical cord is attached. It can be present in the uterus, like the top, side, front, back, or lower area. It is called a low-lying placenta when attached to the lower part of the uterus.

What Affects the Health of the Placenta?

Various factors can impact the health of the placenta during pregnancy.

  • Maternal Age - Placental problems are more common as the age of the mother increases. Women above 40 are at an increased risk.

  • High Blood Pressure- High blood pressure can affect the placenta.

  • Twin or Other Multiple Pregnancies- Mothers carrying more than one baby are at an increased risk of placental problems.

  • A Break in the Water Before Labor- Placental problems increase when the water-containing sac that surrounds the baby (amniotic sac) breaks before labor.

  • Previous Uterine Surgery- Previous uterine surgery, a C-section or surgery to remove fibroids, increases placental issues.

  • Blood-Clotting Disorders- Conditions that either impair the blood's ability to clot or increase its likelihood of clotting can increase the risk of certain placental problems.

What Can Cause a Miscarriage?

Maternal health history can sometimes contribute to a miscarriage. Causes like blocked fallopian tubes caused by past infections or surgical scarring can result in ectopic pregnancies. Some of the common reasons include:

  • Chromosomal abnormalities due to genetic factors.

  • Drugs like non-steroidal anti-inflammatory drugs (NSAIDs) like Ibuprofen and Naproxen, if taken during pregnancy.

  • Uterine abnormalities.

  • Medical conditions like thyroid diseases and diabetes.

  • Certain infections can spread to the reproductive system.

  • Hormonal imbalance.

  • Immune system responses.

  • Cervical insufficiency, where the cervix is weak and cannot hold a pregnancy, causes a miscarriage in the second trimester.

  • The older the woman is, the higher the risk.

  • High blood pressure.

  • Certain uterine or cervix problems.

  • Smoking and alcohol consumption.

  • Being underweight or overweight can create problems in conceiving.


As per the studies above, maternal immune tolerance works on a mechanism that is helpful for the fetus. It develops the baby's immune system through the placenta, which takes nutrition and the ability to fight the foreign bodies of the mother. The mother needs to maintain a healthy lifestyle for the proper growth of their baby, including a healthy diet and exercise without drug abuse.

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Last reviewed at:
26 Jun 2023  -  5 min read




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