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Monday, 27 May 2013

Border Security in the Gut

A couple of weeks ago, when I was returning to the UK, I chose the electronic passport queue, instead of the normal one. You put your "biometric" passport into a machine and stare into a camera. The computer checks whether your travel-weary features match the ones in the passport. It was extremely slow compared to the human immigration officers in the adjacent queue, who were whipping through British passport holders many times faster. To pass the time, I thought about a comparable process that happens in the gut, in which the immune system checks the identity of passing microbes.
The immune system in the gut is very powerful and there are two reasons. Firstly, the gut is such an inviting, food-rich niche. Millions of microbes have evolved to move in and either live in partnership with us or cause unpleasant intestinal diseases. Also the gut wall has a large, vulnerable surface area that microbes can use as a route to infect other regions of the body - typhoid and polio are examples.
All along the gut lining, defence forces are lined up, ready to repel invaders. Huge numbers of immune cells patrol and antibodies are present in vast quantities. Specialised patches of cells take samples of everything that passes, shuffling their catch of the day inwards for scrutiny. 
This facet of the immune system may remind us of immigration control but it's a lot more complex. The billions of molecules scrutinised daily are much more numerous and varied than human faces. They include:

·      Harmless food molecules
·      New, dangerous microbes encountered for the first time
·      Dangerous microbes that have been previously encountered, for which an antibody has already been manufactured
·      Harmless microbes both familiar and unfamiliar
·      Cells belonging to your own body (cheek cells for instance)

This is a monumental task. Far more demanding than devising an immigration system that could  identify every person on the planet without holding up the queue.
It is very important that the gut does not over-react to the millions of friendly bacteria, because such a reaction could cause inflammation. When there is good cause, inflammation is literally a life-saver, reacting rapidly to bacterial invasion of wounds. Longer-term inflammation, on the other hand, is harmful because the powerful chemicals released cause tissue damage.
It has long been suspected that some kind of imbalance in the way the immune system reacts to friendly bacteria lies behind inflammatory diseases of the gut. Immunologists in the University of Pennsylvania have made an important discovery about how the delicate immune balance in the gut can be disturbed. It seems that some very specialised immune cells known as ILCs are needed to keep other immune cells - T cells - under control in the gut, and prevent them from causing inflammation. When ILCs in mice were disabled, inflammation of the gut developed. It seems that ILCs are the ones that can determine the difference between dangerous and harmless bacteria. So under-performing ILCs may be an important cause of gut inflammation.
Work like this furthers our understanding of inflammation in the gut and may eventually lead to new treatments for a range of chronic inflammatory diseases. Or it may not. Tinkering with one aspect of a complex system like the immune system is fraught with difficulty. However it is undoubtedly another intriguing jigsaw piece that contributes to our understanding of how the immune system does its work.