Mechanical Barrier

The concept of mechanical barrier was proposed to explain the lack of immune response in organs such as the brain, cornea, testicles and kidneys. We refer to these tissues as immune privileged sites where an immune response represents a dangerous condition for the tissue. Immune privilege sites are also organs or tissues of the body which, when grafted to conventional (nonprivileged) body sites, experience extended or indefinite survival. Whereas foreign grafts placed at nonprivileged sites are rejected promptly. The pregnant uterus is an example of an immune privilege site.

The first reasonable explanation of immune privilege was proposed by Peter Medawar in the late 1940s.3 Medawar proposed that organs such as the anterior chamber of the eye and the brain resided behind blood:tissue barriers. The existence of a mechanical barrier, (in the brain the blood brain barrier [BBB]), prevents the movement of immune cells in and out of the tissue.4 This barrier created a state of "immunologic ignorance" in which antigens within were never detected by the immune system without. The pregnant uterus was proposed to have a mechanical barrier formed by the trophoblast and the decidua, which prevented the movement of activated T cells from the periphery to the implantation site. Similarly, this barrier would isolate the fetus and prevent the escape of fetal cells to the maternal circulation.

Challenging the mechanical barrier effect theory are studies showing that the trophoblast-decidual interface is less inert or impermeable than first envisioned. Evidence for traffic in both directions across the maternal-fetus interface includes the migration of maternal cells into the fetus and the presence of fetal cells in the maternal circulation.

This is the case of almost all the immune privilege tissues, including the brain's BBB. Conclusive evidence has shown that immune cells circulate through all parts of the brain,5 indicating that immune cells are not deterred by mechanical barriers.

The studies described by Adams and Lee Nelson in this book further demonstrate the bi-directional traffic across the maternal-fetal interface.

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