Reproductive immunology

Reproductive immunology refers to a field of medicine that studies interactions (or the absence of them) between the immune system and components related to the reproductive system, such as maternal immune tolerance towards the fetus, or immunological interactions across the blood-testis barrier. The concept has been used by fertility clinics to explain the fertility problems, recurrent miscarriages and pregnancy complications observed when this state of immunological tolerance is not successfully achieved. Immunological therapy is the new up and coming method for treating many cases of previously "unexplained infertility" or recurrent miscarriage.[1]

Between mother and fetus
Main article: Immune tolerance in pregnancy

The fact that the embryo's tissue is half foreign and unlike mismatched organ transplant, it is not normally rejected, suggests that the immunological system of the mother plays an important role in pregnancy. The placenta also plays an important part in protecting the embryo for the immune attack from the mother's system. Studies also propose that proteins in semen may help woman’s immune system prepare for conception and pregnancy. For example, there is substantial evidence for exposure to partner's semen as prevention for pre-eclampsia, largely due to the absorption of several immune modulating factors present in seminal fluid, such as transforming growth factor beta (TGFβ).[2][3]

Maternal Immune System Changes

The maternal immune system, specifically within the uterus, makes some changes in order to allow for implantation and protect a pregnancy from attack. One of these changes are to the uterine natural killer (uNK) cells. NK cells, part of the innate immune system, are cytotoxic and responsible for attacking pathogens and infected cells. However, the number and type of receptors the uNK cells contain during a healthy pregnancy differs compared to an abnormal pregnancy.[4] Despite the fetus containing foreign paternal antigens, uNK cells do not recognize it as “non-self”.[4] Therefore, the cytotoxic effects of the uNK cells do not target the developing fetus.[4] This provides evidence of fetal-maternal communication regarding immune response during pregnancy.

Sperm cells within a male
Main article: Testicular immunology

The presence of anti-sperm antibodies in infertile men was first reported in 1954 by Rumke and Wilson. It has been noticed that the number of cases of sperm autoimmunity is higher in the infertile population leading to the idea that autoimmunity could be a cause of infertility. Anti sperm antigen has been described as three immunoglobulin isotopes (IgG, IgA, IgM) each of which targets different part of the spermatozoa. If more than 10% of the sperm are bound to anti-sperm antibodies (ASA), then infertility is suspected. The blood-testis barrier separates the immune system and the developing spermatozoa. The tight junction between the Sertoli cells form the blood-testis barrier but it is usually breached by physiological leakage. Not all sperms are protected by the barrier because spermatogonia and early spermatocytes are located below the junction. They are protected by other means like immunologic tolerance and immunomodulation.

Infertility after anti-sperm antibody binding can be caused by autoagglutination, sperm cytotoxicity, blockage of sperm-ovum interaction, and inadequate motility. Each presents itself depending on the binding site of ASA.

Immunocontraceptive vaccine
Main article: Immunocontraception

Experiments are undergoing to test the effectiveness of an immunocontraceptive vaccine that inhibits the fusing of spermatozoa to the zona pellucida. This vaccine is currently being tested in animals and hopefully will be an effective contraceptive for humans. Normally, spermatozoa fuse with the zona pellucida surrounding the mature oocyte; the resulting acrosome reaction breaks down the egg's tough coating so that the sperm can fertilize the ovum. The mechanism of the vaccine is injection with cloned ZP cDNA, therefore this vaccine is a DNA based vaccine. This results in the production of antibodies against the ZP, which stop the sperm from binding to the zona pellucida and ultimately from fertilizing the ovum.[5]

Another vaccine in investigation is one against HCG. This immunization would produce antibodies against hCG and TT. Antibodies against hCG would prevent the maintenance of the uterus for a viable pregnancy therefore preventing conception. Another vaccine that is utilized is the peptide β-hCG that is more specific to hCG and a more rapid and effective response occurs in the absence of LH, FSH, and TSH.[5]

See also

References
  1. Pearson, H. Immunity’s Pregnant Pause. Nature Publishing Group.2002; 420: 265-266.
  2. Sarah Robertson. "Research Goals --> Role of seminal fluid signalling in the female reproductive tract". Archived from the original on 2012-04-22.
  3. Sarah A. Robertson; John J. Bromfield & Kelton P. Tremellen (2003). "Seminal 'priming' for protection from pre-eclampsia—a unifying hypothesis". Journal of Reproductive Immunology. 59 (2): 253–265. doi:10.1016/S0165-0378(03)00052-4. PMID 12896827.
  4. Acar, N., Ustunel, I., & Demir, R. (2011). Uterine natural killer (uNK) cells and their missions during pregnancy: A review. Acta Histochemica, 113(2), 82–91. doi: 10.1016/j.acthis.2009.12.001
  5. Markert U. Immunology of gametes and embryo implantation. Switzerland: Karger; 2005.
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