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.