The immune system is in charge of protecting the body against foreign bodies. This task is modulated during pregnancy since a maternal immune response at this stage could prove fatal for the fetus. Immunosuppression is a down regulation of the components of the immune system, which leaves the organism in state of susceptibility to infections.
During pregnancy, several factors contribute to a full term pregnancy. We need to take into consideration that the fetus is not fully compatible with the mother, which theoretically makes the baby a target for the immune system. One of the major reasons an immune response toward the fetus does not occur is that fetal trophoblast cells do not express MHC Ia antigens. These antigens are responsible for acute rejection of an allograft in humans (Veenstra van Niewenhoven et. al, 2003). Since the fetus does not express them, paternally-inherited MHC antigens will not be recognized as an incompatible allograft by the mother.
Another important factor during pregnancy is thymic involution. As a consequence of this involution, the amount of naïve T cells and thymus secretory factors decreases, thus promoting the survival of the fetus. The few thymocytes available during the pregnancy oversee the integrity of the mother’s immune system. However, the mechanism for this process still remains unknown.
Innate immunity is the mechanism that initially recognizes and responds to the presence of a pathogen; it does not increase with repeated exposure and does not discriminate between groups of similar pathogens. This system is neither specific nor precise, and its most important aspect related to pregnancy is that it does not create an immunological memory. Lack of such a memory benefits the fetus because it prevents future attacks of the immune system during the gestation period. Another factor that contributes to the tolerance of the non-compatible fetus is the shift away from type 1 cytokine production during pregnancy.
One major concern during pregnancy is the blood type differences between fetus and mother. Alloimmunization most often results from Rhesus (Rh) incompatibility between mother and fetus. If the fetus has a different type of blood, the mother may recognize it as a pathogen and in the following pregnancy with Rh factor incompatibility, the mother’s immune system will attack the red blood cells of the fetus. If the mother is Rh negative, she will not tolerate an Rh positive fetus and can create antibodies against the fetal blood. These antibodies will attack the RBC’s of the next Rh incompatible fetus, and the fetus will develop anemia. This hemolytic anemia can cause mental retardation, illness and in extreme cases newborn death. It is a type 2 hypersensitivity that involves an antibody-mediated reaction, which involves IgG antibodies against cell surface receptors.
Our entire discussion is focused on how the fetus survives during pregnancy. Consequently, it is not surprising to see decreased aggressiveness of autoimmune diseases in immunomodulated pregnant women. Thus, many of the mechanisms of immunosuppression remain unknown, yet they have proved to be highly efficient in protecting the fetus.
Clinical Applications:
An important clinical application in pregnancy immunology is immunotolerance, the basis for successful implantations. Pregnancy is not a classical graft vs. host reaction; however, it involves specific compounds derived from the embryo which modulate the immune response. This concept has been very important in the success of egg donation programs. However, it has its risks because egg donation is associated with a high incidence of pregnancy complications such as pre-eclampsia and intra-uterine growth restriction. Pre-eclampsia in mothers that participate in egg donation programs may occur mainly because the mother may lack the receptors for the proteins the placenta is using to down regulate the maternal immune system's response, therefore, lack of established immunological tolerance, resulting in an immune response against paternal antigens from the fetus and its placenta. However, gene sharing (HLA sharing) results in a more effective immunotolerance, decreases complications, and aids in avoiding miscarriage.
Multiple Choice Questions:
1. Expression of which of the following cytokines is correlated with impairment of embryonic and fetal developments(Choose best answer):
a. IL-1
b. IL-2
c. IFN-α
d. IL-17
2. One of the major reasons an immune acute rejection (similar to that of an allograft) toward the fetus is avoided is the fact that:
a. Involution of maternal thymus during pregnancy
b. Innate immune response of the mother is downgraded
c. Fetal trophoblast cells do not express MHC Ia antigens
d. Increase in the amount of naïve T cells and thymus secretory factors
3. Rhesus incompatibility is a type of ____________ that involves the attack of _____________.
a. Alloimmunity, red blood cells of fetus with same Rh as mother
b. Autoimmunity, red blood cells of fetus with different Rh than mother
c. Alloimmunity, red blood cells of fetus with different Rh than mother
d. Autoimmunity, white blood cells of fetus with same Rh as mother
Discussion Questions:
1. What would happen if the mother was not immunosuppressed during pregnancy?
2. How is an immune response towards the fetus avoided?
3. What is innate immunity, and how does it benefit the fetus?
Images:
Alloimmune hemolytic anemia, Rh incompatibility. Blood film. Note the polychromatophilic macrocytes (reticulocytes), the nucleated red cells, and the ejected erythroblast nuclei. Spherocytes are present. The intense erythroblastosis (nucleated red cells in the blood) is characteristic of Rh-mediated alloimmune hemolysis.
A: Rh-negative woman before pregnancy. B: Pregnancy occurs. The fetus is Rh-positive. C: Separation of the placenta. D: Following delivery, Rh isoimmunization occurs in the mother, and she develops antibodies (S) to the Rh-positive antigen. E: The next pregnancy with an Rh-positive fetus. Maternal antibodies cross the placenta, enter the fetal bloodstream, and attach to Rh-positive red cells, causing hemolysis.
Thymic involution and loss of functional thymic tissue. (A) With increasing age, functional thymic tissues (medulla and cortex) are replaced by fat.
References:
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