The Online Medical Dictionary (2008) defines pregnancy as the condition of having a developing embryo or fetus within the body, following the union of an ovum and a spermatozoon. This, however, is more complex to a woman’s body than it seems, from an immunological standpoint. The body has anatomic or physiological barriers that protect it from chemicals and other potentially dangerous molecules. The so-called placental barrier, is one of such barriers, it impedes certain chemicals, while allowing fat-soluble chemicals to cross it. (Britannica Encyclopedia, 2008) Besides the placenta, there are other complex mechanisms occurring throughout a woman’s body for her to successfully support her pregnancy, despite considering the fetus as an allograft. Nonetheless, the body’s immune system sometimes identifies the fetus as a foreign agent, because of the genetic influence of the father’s chromosomes and creates autoantibodies that “attack” it, thus the importance of alloimmunity.
One of the previously mentioned mechanisms directly relates to immunoglobulins, especially IgG. IgG is the only immunoglobulin capable of crossing the placenta to provide protection for the fetus. It is part of a chain of events that suppress the immune system while activating protection for the fetus. When the immune system is not suppressed, there will be lethal consequences for the unborn child, or the child could suffer of an autoimmune disease. Some of the factors involved in autoimmune disease include: fetal factors, such as properties in trophoblast cells (outermost layer of cells of the blastocyst that attaches the fertilized ovum to the uterine wall and serves as a nutritive pathway for the embryo), and altered MHC Class I expression (group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances). There are also maternal factors such as specialized uterine natural killer cells and a shift of T-helper cell cytokine profile from Type T- helper I to T-helper II. Helper T cells do not directly kill infected cells, as cytotoxic T cells do. Instead they help activate cytotoxic T cells and macrophages to attack infected cells, or they stimulate B cells to secrete antibodies. Helper T cells become activated by interacting with antigen-presenting cells, such as macrophages. When these systems are activated against the fetus, a spontaneous abortion can occur, however, if the fetus successfully developed and subsequently born, there is a possibility for the fetus to suffer of an autoimmune disease later in life.
Alloimmunity is responsible of alerting the mother to react to the fetus (an allograft), as a baby, not as an infection, thus facilitating the synthesis of necessary antibodies and general support of the fetus. Since a father puts HLA (human leukocyte antigens), which are different from the mother’s on the placenta, it must be recognized as a foreign being. When this happens the mother makes an antibody called a “blocking antibody” that attaches to the placenta and makes it look to her like a “good invader”. In this circumstance, the antibodies that the mother produce do not kill the fetus; instead it protects the baby and makes the placental cells grow faster, thus providing continued support for the pregnancy. (Beer, 2008)
Medical Application
Reciprocal cell traffic between mother and fetus during pregnancy gives rise to postpartum fetal–maternal lymphohematopoietic microchimerism (the presence of two genetically distinct and separately derived populations of cells), which is frequently detected in blood or tissue from healthy individuals. Microchimerism has been implicated in the pathogenesis of autoimmune diseases and tissue repair, recent clinical experiences have suggested the association of microchimerism with acquired immunologic hyporesponsiveness to non-inherited maternal HLA antigens (NIMAs) or inherited paternal HLA antigens (IPAs); T cell-replete HLA-haploidentical hematopoietic stem cell transplantation from a microchimeric IPA/NIMA-mismatched donor confers relatively lower incidence of severe graft-versus-host disease, thus fetal cord cell transplantation an effective way to avoid transplant rejection.
Questions:
Multiple choice questions:
1. A couple is planning to have their first child, but their main concern is that the father's HLA is different from his wife's. Why is alloimmunity necessary?
a. to protect the fetus
b. to attack the fetus
c. to allow certain chemicals to cross the placenta
2. All immunoglobulins can freely penetrate the placenta.
a. True
b. False
3. During pregnancy, the maternal immune system reacts towards the foreign tissue, but instead of triggering rejection, it tolerates, supports and regulates its development. The immunological mechanisms allowing the fetus to grow and survive are complex, and sometimes may identify the fetus as foreign. How is the fetus perceived by the women’s body?
a. as an xenograft
b. as an holograph
c. as an allograft
d. as an autograft
Discussion Questions:
1. A 25 year old woman is trying to get pregnant and through each attempt she has had three miscarriages. What can be a possible cause for the three miscarriages?
2. A 28 year old woman is four months pregnant; she went to a prenatal visit where her physician completed some test. In one of the results it showed low levels of IgG. What is the possible clinical application for such value towards the fetus?
3. A couple is trying to have a baby for a couple of months now. State the name of the process that helps the mother reacts negatively against the baby and prejudiced the pregnancy and what it consist of?
- Janeway CA, Travers P, Walport M, Shlomchik MJ. Immunobiology. 6th ed. New York, NY; Garland Science Publishing; 2005.
- On-line Medical Dictionary. The Dept. of Medical Oncology. Available at: http://cancerweb.ncl.ac.uk/cgi-bin/omd?action=Home&query=lactose+intolerance.html. Accesed April 29, 2008.
- Garland Science. Taylor and Francis Group. Available at: http//www.garlandscience.com. Accesed April 30, 2008.
- Encyclopedia Britannica Online (2008). Accessed May 18, 2008.
- Beer A., Consequences of Recurrent Pregnancy Loss: An Introduction to Categories 1-5 Immune Problems.
- Ichinone T., Teshima T., Matsuoka K., Maruya E., Saji, H., Fetal-maternal microchimerism: impact on hematopoietic stem cell transplantation. Science Direct – Current Opinion in Immunology (2005). Accessed May 18, 2008.
