The womb is a sterile environment and thus no antigens, so the fetal immune system does not need to function. Thus, it is safely suppressed to reduce any potential reactions to the mother’s cells which could be interpreted by the developing fetus as foreign (non-self). Meanwhile, fetal cells are crossing the placenta and can be detected in Mom between the fourth and fifth week of pregnancy, and will remain for years, even decades, after she has given birth. The presence of these genetically distinct fetal cells from baby to Mom is called microchimerism (thought to enhance mother’s milk). This exchange of cells from the fetus to the pregnant woman provides a possible explanation as to why a mother’s immune system does not reject the growing fetus.
It’s fascinating to realize that the immune system is intimately involved in the association of the mother and the fetus during pregnancy. The immune system of the mother and fetus are precisely timed to achieve the best outcomes for both. The mother’s innate immune system response is aggressive during the first 12 weeks of the pregnancy to support and establish successful implantation of the embryo. The womb is lined with the mother’s immune cells and that creates a process called “passive immunity” where chemicals (particularly things like immunoglobulins IgG and IgM which we’ll be talking about in a moment) help the fetus get fully established. After that, during the following 15 weeks of the pregnancy, the mother’s immune system suppresses itself to allow for the fetal cells to grow as the fetus develops its own immune system (virtually two immune systems functioning in one body). Finally, an aggressive immune system response by the mother returns near delivery, when certain chemicals Mom produces called proinflammatory mediators (more to come on those) help with the labor response.
The majority of unique genes in human holobionts (defined in Blog #6) are found in microbiomes, and mothers are responsible for transferring most of these to their offspring during birth, breastfeeding, and physical contact. Thus, mothers are likely to be the primary providers of the majority of genetic information to offspring via mitochondria and the microbiome. It’s also an interesting phenomenon where the DNA of those fetal cells, male or female is detectable in the mother (especially her brain) for the rest of her life. This is referred to as “pregnancy brain” and is believed to have lifelong effects (positive, like added protection, and negative, like lifelong potential autoimmune effects in the mother).
The distinctions and superiority of the female immune system begin even earlier than its ontogenetic evolution. Through the process of passive immunity, maternal-derived IgG antibodies are transferred and shared in fetal circulation prior to birth, through the placenta and through mother’s milk following birth. While the risk associated with pathogenic exposure is attenuated by passive immunity, the infant's immune system begins to “learn” about the local disease ecology and acquires specific immune defenses that will endure beyond the period when passive immunity is no longer operative. In a sense, since the development of specific immunity is a time-dependent Darwinian process, passive immunity can be conceptualized as a transient Lamarckian process of inheritance of acquired characteristics, whereby the mother shares her knowledge of the local disease ecology to provide a period of buffered pathogen exposure while the infant builds its own repertoire of defenses through a Darwinian process of somatic evolution. Thus, to minimize the potential for off-spring infection, natural selection has evolved an increased antibody production in females.
Beyond the embryology, after birth the immune system continues to develop robustly until about age seven to eight when it reaches its strongest levels. At that point, general health, proper diet, and exercise will maintain a strong immune system for many years thereafter. But as we age, to be expected as with so many things, the system will begin to slow down a bit in response time and of course, it can be dangerously impaired with any form of immunocompromising disorders. But, by and large, the immune system continues to be our principal defense mechanism throughout life, notwithstanding increased risks of certain diseases (e.g., cancers) due to its slower response times with aging.
Discussion Questions:
Microchimerism is a possible explanation as to why a mother’s immune system does not reject the growing fetus. There are numerous others as well. Can you identify some of them?
There are numerous elements of Darwinian natural selection and Lamarckian inheritance influencing pregnancy. Which would you consider the most significant examples?
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