Foetal immunity protects females

06 March 2011
Posted by Chris Smith.

The female genital tract uses a foetal gene to protect itself from infection during adulthood, new research has found.

Mucosal surfaces, like the genital tract, mouth, gut and eyes, are important portals of entry for pathogens attempting to penetrate our immunological defences.  They are known to be defended by a class of antibodies known as IgG as well as a number of other chemical armaments, but exactly how the IgG antibodies reach the skin surface where they can neutralise attacking microbes, no one was sure.

Foetus in ultrasoundNow, writing in PNAS, University of Maryland researcher Xiaoping Zhu and his colleagues have discovered that adult cells use a gene normally found working in the placenta to do the job.  The gene in question is called FcRn and it's role during pregnancy is to grab antibodies from the mother and add them to the baby's bloodstream.  This temporarily provides the newborn with so-called "passive protection" from the mother while its own immune system gains momentum after it is born.

Reasoning that the same gene might be at work in the genital tract, the Maryland team tested a range of cultured cells include uterine, cervical and vaginal lines, confirming the presence of high levels of FcRn activity.

Next, to confirm that the gene was actually functional, they incubated cultured cells that were expressing FcRn with IgG-class antibodies.  Intriguingly the antibodies were picked up and passed from one side of the cell to the other, a process which ceased when the researchers disabled the FcRn gene.

They were also able to confirm the same results in mice, including demonstrating that chemically-labelled antibodies are transported onto the mucosal surfaces of the genital tract by the FcRn gene.  When this was genetically "knocked out" from the mice, the antibody movement was arrested.  These knockout animals were also highly susceptible to infection with a strain of herpes virus that transmits genitally.

Knowing how this process now works, the researchers argue that it may be possible to exploit this system to produce better vaccines capable of boosting immune defences at mucosal surfaces and hence better protect patients against a range of infections, not least HIV and other sexually-transmitted diseases.

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