Special Topics in Immunology:
Reproductive Immunology
Figure 1 - Screenshots from Shared Journey and Reproductive Immunology Associates websites. |
Figure 2 – Model for immunological basis of Recurrent Spontaneous Abortion. From www.rialab.com/miscarriages_prevented.php
Reproductive immunology is an important and expanding science that addresses many medical issues as stated in the introduction. The Clinical Cases that are presented in the next section, portray some classical examples of diseases know by the general public that are finally being understood and in some cases treated with success. But these diseases are only a fraction of conditions that are studied in the field of reproductive immunology.
Clinical Correlations
Recurrent Spontaneous Abortions
One factor related to miscarriage is the natural killer (NK) cells which seem to have a role in recurrent spontaneous abortions (RSA). The major role of NK cells is to cause an inflammatory response mainly by the release of IL-10 in the endometrial layer thereby increasing angiogenesis in the decidua. Thus, NK cells normally assist in early fetal development. Studies show that women with RSA have increased NK cell counts.[vi] Hyperactive NK cells probably cause RSA by damaging maternal endocrine cells responsible for producing and secreting the hormones essential for pregnancy. Another hypothesis that is gaining much acceptance is that involvement of the complement system, causes an inflammatory reaction that produce placental hypoxia eventually leading to abortion.[vii] (See figure 2)
Gestational Diabetes
Reproductive immunology has many areas of study, including women’s diseases related to pregnancy. For example Gestational Diabetes (GD) is an insulin intolerance that is recognized during pregnancy without previous diabetes history. Studies show that GD is related to fetal monocyte activation by the mother’s immunoglobulins against paternal HLAs, as is the case of Rh Hemolytic Disease of the Newborn and Pre-eclampsia (hypertension and generalized edema in the pregnant woman).[viii] Scientist hypothesized that by some defect in the barriers dividing the mother and fetus, the mother’s immune system come in contact with antigen particles that are really biological structures from the fetus.
Anti-Sperm Antibodies
As part of fertilization and conception problems, one of the targets in recent studies is the Anti-Sperm Antibodies (ASA). These antibodies can impair the fertilizing capacity of human spermatozoa, acting negatively on sperm motility, cervical mucus penetration and in vitro gamete interaction. These have also been linked to semen hypersensitivity, a condition in which the woman experiences the symptoms of any other allergy. Few treatments are thought to be successful. Treatment options focus on decreasing ASA production and removing ASA already bound to sperm. The first is based on a treatment with corticosteroids, and the other by in vitro capacitation of sperm where it is possible to remove the entire immune complex without damaging the cell.[ix]
However, some cytokines are released within the sperm that help to regulate the immune system preventing a response against the embryo. Studies conclude that TGF is a potent immune-deviating cytokine with pivotal roles in inducing active immune tolerance in mucosal and peripheral tissues. Seminal TGF deposited in the female tract at insemination is activated and interacts with female tract cells to elicit an inflammatory cascade. It is reasonable to postulate that seminal antigens are shared by the conceptus, seminal TGF may act to facilitate induction of maternal immune tolerance to conceptus antigens and thereby promote implantation success.[x]
Discussion Questions
- What is the role of antisperm antibodies in infertility?
- What other immune related conditions or cytokines might cause infertility?
- What about immunosuppression in pregnant women? How are women immunosuppressed and why is this important to the health of the fetus?
Multiple Choice Questions
- What is true about NK cells function in pregnancy?
- NK cells play an important role in the 3rd trimester.
- NK cells are hypersensitive in pregnant women.
- NK cells have no role in normal pregnancy
- NK cells are important in preparing the endometrial layer for implantation.
- According to the CDC, what percentages of people in reproductive age are affected by infertility?
- 15
- 7
- 39
- 12
- What article would you find classified as a study of reproductive immunology?
- Toll like receptor signaling and pre-eclampsia
- Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients
- Women with Multiple Implantation Failures and Recurrent Pregnancy Losses have Increased Peripheral Blood T Cell Activation
- CD57+ Cells and Recurrent Spontaneous Abortion
References
[i] About Journal of Reproductive Immunology. Journal of Reproductive Immunology: The International Journal for Clinical and Clinical Reproductive Immunobiology. Available at: http://www.journals.elsevierhealth.com/periodicals/jri. Accessed April 11, 2010.
[ii] Assisted Reproductive Technology: Home. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/art/. Accessed April 11, 2010.
[iii] Shared Journey. Shared Journey: Your path to fertility. 2010. Available at: http://www.sharedjourney.com/index.html. Accessed April 11, 2010.
[iv] Reproductive Immunology Associates. 2010. Available at: http://www.rialab.com/ Accessed April 11, 2010.
[v] Berek, Jonathan, & Novak, Emil. (2007). Berek & Novak's Gynecology. Hong Kong: Lippincott Williams & Williams.
[vi] Kwak-Kim, J and Gilman-Sachs, A. Clinical Implication of Natural Killer Cells and Reproduction. Am J Reprod Immunol. 2008; 59: 388-400.
[vii] Hahn, Sinuhe, Anurag Kumar-Gupta, Carolyn Troeger, Corinne Rusterholz, and Wolfgang Holzgreve. "Disturbances in placental immunology: ready for therapeutic interventions?." Springer Semin Immun. 2006.27 (2006): 477-493. Print.
[viii] Steinborn A., Saran G, Schneider A, Fersis N, Sohn C, Schmitt E. The Presence of gestational diabetes is associated with increased detection of anti-HLA-class II antibodies in the maternal circulation. American Journal of Reproductive Immunology, 2008: 56, 124-134.
[ix] Lombardo, F, L Gandini, and A Lenzi. "Antisperm immunity in assisted reproduction." Journal of Reproductive Immunology. 2004.62 (2004): 101-109. Print.
[x] Robertson S.A., Ingman Wendy V., O’Leary Sean, Sharkey David J., Tremellen Kelton P. "Transforming growth factor β—a mediator of immune deviation in seminal plasma"
Journal of Reproductive Immunology, Volume 57, Issue 1, Page 109
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