Immunology of the genital tract - a review

The objective of this work was to systematically review and discuss recent studies and articles dealing with the subject of the immunology of female genital tract mucosal tissue. The emphasis hereby lies on the evaluation of studies concerning the basics of female reproductive immunology, research on immunology of the most important genital infections and vaccination strategies, immunologic principles at the fetomaternal interface during normal pregnancy and its complications as well as on immunologic data on infertility and immunocontraception. It is now established that the mucosal immune system is a distinct and separate component of the host`s immune apparatus and differs from the lymphoid tissues in peripheral sites. Furthermore, despite some common features, the female genital tract mucosal system displays some distinct characteristics which outlines its special role. Analysis of the female genital tract indicates that the key cells of the innate and adaptive immune systems are present and functionally responsive to antigens; however, there is a certain degree of compartmentalization within the tract. The identification of TLRs in the fallopian tubes, uterus, cervix, and vagina and the presence of ECs, macrophages, DCs, NK cells, and neutrophils throughout the reproductive tract along with their responsiveness to selected PAMPs indicate that the female reproductive tract has evolved to meet the challenges of STDs, while at the same time supporting an immunologically distinct fetal placental unit. To meet these diverse challenges, innate and adaptive immune system in the female genital tract are precisely regulated not only by a network of cytokines and chemokines, but also by the sex hormones estrogen and progesterone. Understanding the specialty of the genital tract immune system is of critical importance, because STDs are and will be a major worldwide health problem. Despite extensive efforts, only limited success has been achieved in dealing with a growing list of STDs. The role of immune factors in the control of genital viral and bacterial infections appears complex and needs further studying, also with respect to creating vaccines. Despite the recognition that innate immunity as the first line of defense and adaptive immunity, especially Th1 immune responses, play a critical role in preventing infection and in limiting viral replication, factors such as antimicrobials and TLRs that contribute to the mucosal response in the female genital tract have only recently begun to receive attention. Further studies are also needed to elucidate the relationship between mucosal immunity, the hormonal environment, and response to pathogen challenge. More data must be collected on the mechanisms of immune evasion by several pathogens such as HSV, N. gonorrheae or Chlamydia. While considerable information can be obtained from animal experiments, important differences in the physiology of reproduction and the immune sytem result in the need for studies in humans. Further knowledge on female tract immunology will also impact on immunological approaches to contraception, immunological infertility and the immunological aspects of pregnancy. This does not only involve new options for diagnostics but also for treatment of pregnancy complications such as preeclampsia, preterm birth and early pregnancy loss as well as for infertility. Pregnancy involves maternal tolerance of the semiallogenic histoincompatible fetus and is characterized by the enhancement of the innate immune system and suppression of the adaptive immune response, probably with progesterone as the important regulator. In opposite to normal pregnancy, improper immune responses and an unbalanced cytokine network may characterize implantation failures, pregnancy loss and obstetric complications. These are the presence of elevated Th1/Th2 cell ratios, high concentrations of Th1 cytokines, elevated NK cell cytotoxicity and levels, and emergence of various autoantibodies. These immunological approaches needs to be investigated and evaluated further with respect to widening of treatment options by modification of immune responses.