The Role of the Immune System in Pregnancy

The Role of the Immune System in Pregnancy 

Pregnancy is an extraordinary biological process that requires the body to perform a delicate balancing act. One of the most fascinating aspects of this process is how the immune system adapts. Normally, the immune system is designed to identify and attack anything that appears foreign such as viruses and bacteria. Yet during pregnancy, the body must tolerate the presence of an embryo, which carries genetic material from both parents and is therefore partly “foreign.” 

Over the last 10 years, at the CHR, we learned that when an embryo implants into the uterus and starts digging into the endometrium and starts growing, for at least ten days and maybe even longer, this embryo does all this preprogrammed genetically without any support from the mother. Only after the embryo has invaded deep enough to establish contact with the maternal vasculature does it begin to receive nutrients and information from the mother. 

This is important because every embryo that implants is like a small organ transplant that the mother receives. If a woman were to receive a renal transplant from her husband, in almost all circumstances her body would reject it unless she were treated with immunosuppressive drugs. Yet the tiny “transplant” called an embryo usually does not get rejected. 

This is because nature has developed a system that allows humans to tolerate this kind of invasion under certain circumstances, though not always. Nature essentially created a mechanism that enables the mother’s body to accept something that is partially foreign. 

Symbolically speaking, an embryo makes its way into the endometrial cavity. In a spontaneous pregnancy, the embryo travels there from the fallopian tube. Sperm and egg meet at the far end of the fallopian tube where fertilization occurs. Over the next few days, the developing embryo slowly moves into the uterus and floats around in the uterine mucus for about 48 hours before implantation. In IVF, the process is very similar, except the embryo does not come from the fallopian tube. Instead, it is introduced through the vagina and cervix, and doctors place it into the uterine cavity using a catheter. Once there, the embryo again spends roughly 48 hours in the uterine environment before it either implants or fails to implant. 

However, not every embryo that reaches the uterine cavity implants. The embryo must first send specific signals to the mother’s immune system through certain cells in the endometrium. In a sense, the embryo is signaling, “I’m here - please let me in.” The maternal immune system then evaluates the embryo through these endometrial cells. If the embryo appears to be viable, the immune system does something remarkable: it reprograms itself. 

Normally, the immune system’s job is to reject anything foreign that enters the uterus. Yet when this tiny invader arrives, a properly functioning immune system can allow it to enter. This permission is extremely selective. If the system were not highly specific, the embryo could bring bacteria or viruses with it, and infections would occur regularly. Instead, the maternal immune system undergoes a very precise reprogramming process that makes the embryo immunologically “invisible.” After this reprogramming, the immune system no longer recognizes the embryo as foreign, which allows the embryo to implant and continue growing, eventually developing into a baby. 

What makes this process so fascinating is that the immune system is capable of such a transformation. Once implantation begins, the embryo essentially digs into the uterine lining for about 10 to 14 days on its own. During this time, the mother contributes very little except for one factor: her immune system must respond appropriately to the signals from the embryo and reprogram itself. 

This immune reprogramming is the very first critical step. If it does not occur completely independent of any other factors in the maternal system, the embryo would simply be rejected. Long before maternal hormones influence the success of a pregnancy, the mother’s immune system must function properly. At its core, pregnancy starts with a highly specialized immunological adaptation that allows the mother’s body to tolerate and support a genetically distinct embryo.