Recurrent Early Pregnancy Loss - 5 - Introduction to Immunologic Causes
Under ‘normal’ conditions, our immune systems are designed to protect us from things that are foreign to our bodies and also to recognize that which is ‘self’ and allowing it to elude immune destruction (‘tolerance’). There are many components of the immune system. The first line of defense is the ‘innate’ immune system. This is comprised of cells (macrophages, neutrophils, natural killer cells), cytokines (chemicals produced by these cells), and one arm of the complement system that are capable of ‘recognizing’ something foreign, limiting its invasion, and eliminating it but without necessarily producing a specific memory for the immune response to the invader. This is sometimes referred to ‘nonadaptive immunity.’
The other side of the immune system results in the production of specific antibodies (made by B-lymphocytes) and clones of T-lymphocytes, also directed against the specific invader, that are capable of ‘remembering’ the invader and, therefore, can more quickly respond if they are attacked again by the same (or in some cases, a similar) organism. This ‘specific’ immunity is often termed 'adaptive immunity.’ When tissue destruction occurs, as the result of either a specific or a nonspecific immune response, the blood clotting system is often activated as well. This may help to ‘finish off’ the invading organism or limit its access to oxygen and spread throughout the body by clotting off the blood supply at the site of the battle. This is the ‘synergy’ between the immune system and the blood-clotting system referred to above in the first paragraph.
The implanting embryo inherits and expresses characteristics from both the mother and father. Although certain major ‘transplantation antigens’ are not expressed on the invading placental tissues, the maternal immune system, both nonadaptive and adaptive, appears to be able to recognize the fetal tissues as ‘foreign’, but in a way that facilitates, but limits, the invasion, permits remodeling of the spiral arterioles of the endometrium, and then 'tolerates' the persistence of these fetal tissues, lining the spiral arterioles and the placenta itself, throughout the duration of the pregnancy. It would appear that if the maternal immune response either under-reacts or over-reacts, the implantation, placentation, and ultimate survival of the fetus are in jeopardy. The balance is both remarkable and delicate. As we have mentioned in one of our earlier posts on the subject of miscarriage, a proper maternal immune response requires some degree of ‘education’ and this might only come at the expense of an otherwise ‘normal’ embryo, accounting for the high frequency of ‘first pregnancy’ miscarriages in early pregnancy and perhaps the higher incidence of pregnancy-induced hypertensive disorders (preeclampsia) more often seen in first pregnancies that survive the first trimester.
In the next post, we will address specific abnormalities of the maternal immune system and clotting system that may be related to recurrent early pregnancy loss…