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Reproductive immunology: immunity and the developing foetus

Fiona M. Menzies, University of Glasgow, UK

A unique problem

Pregnancy presents a complex immunological problem for the mother. Cells and molecules of the immune system interact in such a way as to prevent the rejection of the semiallogenic foetus (i.e. sharing only 50% genetic relatedness with the mother, the remainder being with the father) and support its growth and development. In 1953 Sir Peter Medawar, a pioneer in the field of transplantation biology, presented a lecture in which he asked the following question:

“The immunological problem of pregnancy may be formulated thus: how does the pregnant mother contrive to nourish within itself, for many weeks or months, a foetus that is an antigenically foreign body?”

To this day, this question remains relevant and, as yet, incompletely answered and is the foundation of the field of reproductive immunology.

Immune cells at the maternal-foetal interface

A number of immune cells have been identified within the maternal-foetal interface, including uterine Natural Killer cells (70%), macrophages (20%), T cells (including CD4+, CD8+, gd T cells, regulatory T cells) (10%), dendritic cells and B cells (few). The numbers of these cells and roles that they play differs throughout the various stages of pregnancy.

Protection of the conceptus

Several factors have now been found to be involved in protection of the developing foetus from attack by the maternal immune system, mainly:

  1. The anatomical barrier between baby and mother,   through separate circulatory systems within the placenta (Figure 1).
  2. The  antigenic  immaturity of the fetus. Major histocompatibility (MHC) antigen expression is reduced  on trophoblast cells on the foetal side of the placenta.
  3. Development of an immunosuppressive environment within the uterus. Immune  cell reactivity  within the uterus is substantially reduced during pregnancy, thus preventing adverse immunological responses against the conceptus. Several mechanisms are involved including the skewing of both the local and systemic immune environment towards a Th2 profile, due to the influence of the female sex hormones (oestrogen and progesterone). In addition, the expression of certain molecules (HLA – G, E, C) on trophoblast cells inhibit the activation  and  proliferation of uNK cells and CD8+ T cells.
Reproductive immunology - figure 1

Figure 1. The Placenta: The Maternal-Fetal Interface

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