Special Cells Protect Baby from Mom’s Immune System

You’ve probably been hearing a lot about the immune system lately, what with the ongoing pandemic. But the immune system, which is the body’s defense mechanism against invaders like bacteria, viruses, and cancer, also plays a role in pregnancy. It turns out that an entire person growing inside you can be a real trigger for your immune system, as the baby’s tissues come into contact with your tissues in the uterus. If your body isn’t able to discern what is your “self” and what is an invader, it can mean that you could get very sick. But in the case of pregnancy, where the growing baby is clearly not “self” but needs to be left alone to grow, the immune system needs help.

One of the most well-known immune complications of pregnancy is so-called Rh incompatibility, where baby’s blood is positive for the Rh factor (a small molecule that hangs out on the surface of red blood cells) and the pregnant person’s blood is negative. The presence of the Rh factor in baby’s blood means that the parent’s immune system will make antibodies (molecules that recognize other molecules and direct the immune system to attack the cells bearing those molecules) to the Rh factor, which can cause recognition of the fetus’s blood cells and severe anemia in the fetus during future pregnancies. This anemia can make for a sick baby in utero, but it can also lead to miscarriage. If you’ve been pregnant before, even if the pregnancy ended in a miscarriage or abortion, and you have a negative blood type, it’s possible that your immune system has already developed antibodies to the Rh factor.

In the case of Rh incompatibility, there is a shot you can get during pregnancy, called RhoGAM, which stops your immune system from responding to Rh factor in baby’s blood, but other immune system issues can come up during pregnancy. For instance, it’s possible that the immune system plays a role for people who have recurrent miscarriages (two or more miscarriages in a row). And in cases where pregnant people have an autoimmune disease, such as rheumatoid arthritis, sometimes pregnancy can improve symptoms.

It’s clear that there are multiple interactions between the immune system and pregnancy, but researchers don’t always understand how those interactions look and what effects they have. For example, there is some evidence that immunological incompatibility—when the mother’s immune system recognizes the fetus as non-self—is part of what can trigger preeclampsia. [1] It’s therefore important for researchers to try to understand how the immune system interacts with pregnancy to help prevent pregnancy complications.

In a study that was recently published in the journal Science Immunology, a team of researchers showed that there are special immune cells that teach the rest of the immune cells that the baby is “self.” [2] In a recent opinion piece in The Conversation, coauthors Eva Gillis-Buck, James Gardner, and Tippi MacKenzie, who are all physicians at the University of California, San Francisco, explain that these cells provide a kind of continuing education to teach the pregnant person’s immune system to recognize the fetus as self rather than a foreign invader. [3] While the researchers showed in mice that the educator cells are necessary for a healthy pregnancy, they don’t yet know how these cells do their job. And it’s likely that the cells work the same way in humans, but future research may show exactly how the cells work in people.

Learning more about how the immune system works in pregnancy is also relevant in a pandemic. It’s now known that pregnant people who contract COVID-19 are at higher risk having more severe disease. This risk is likely at least in part due to the suppression of the immune system that’s necessary for the health of the baby. Vaccines are therefore particularly important for pregnant people and also pass some protection along to the baby that they’ll be able to carry with them after birth.

  1. A. Inkeri et al., “The Immunogenetic Conundrum of Preeclampsia,” Frontiers in Immunology, doi:10.3389/fimmu/2018/02630, 2018.
  2. Gillis-Buck et al., “Extrathymic Aire-expressing cells support maternal-fetal tolerance,” Science Immunology, doi:10.1126/sciimmunol.abf1968, 2021.
  3. Gillis-Buck et al., “Specialized cells maintain healthy pregnancy by teaching the mother’s immune system not to attack developing fetus,” The Conversation, 2021.
Abby Olena
Dr. Abby Olena has a PhD in Biological Sciences from Vanderbilt University. She lives with her husband and children in North Carolina, where she writes about science and parenting, produces a conversational podcast, and teaches prenatal yoga.

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