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.

http://bit.ly/10ouz0l

Immune System Even Cleverer Than We Thought

In any branch of science there are moments when conventional wisdom is overturned. One of those moments has just occurred in immunology as a result of research at Stanford University. Our previous understanding was too simplistic. Things are even more complicated than we thought.

For years now everyone has believed that lymphocytes can learn to recognise specific molecules but that each type of lymphocyte can only learn a single lesson. One kind of lymphocyte can learn to recognise measles virus, another can learn to spot whooping cough bacterium on sight and another can only be activated by a particular protein made by prawns. Once a lymphocyte has had its initial exposure it will produce memory lymphocytes (CD4 cells) that will hang around for the rest of your life, waiting patiently to deal with a second encounter. This is how adaptive immunity and, of course, vaccination works. 

But the one lymphocyte = one lesson theory has just been blown out of the water. It seems that lymphocytes can generalise their learning.

The human brain can generalise easily. Learner drivers are taught to negotiate road junctions. Once the basic skill is there, they will be able tackle all kinds of road junctions. No two junctions are identical but nevertheless the competent driver tackles them all confidently. The learning has been generalised.

Now it seems that memory lymphocytes have some ability to do the same kind of thing. They are even cleverer than we thought. They can recognise not only the microbe that first activated them, but some other types as well.

We knew the immune system was magnificently complicated and now we have to acknowledge the existence of a whole new level of complexity. This new knowledge may shine a light several aspects of how the immune system learns about its environment, such as how benign bacteria help the immune system to develop in childhood.
http://www.sciencedaily.com/releases/2013/02/130207131602.htm

Hygiene Hypothesis out and "Old Friends" are in

For some years now, increased rates of childhood asthma and eczema have been observed and the finger of suspicion has pointed to a lack of microbes in overly-clean homes. This idea is known as the hygiene hypothesis.

A recent report from the International Scientific Forum on Home Hygiene has concluded that this hypothesis is not correct.

It seems that microbes - or rather a lack of them - may well be implicated in the increase of allergies but it is not a reduced quantity of bacteria, viruses and intestinal worms that seems to be the problem.

We all have a vast population of "friendly" microbes that live on our skin and in our body cavities - nose, mouth, gut and so on. The bacteria alone are said to outnumber our body cells by ten to one. Without exposure to this vast array of microscopic life, we cannot be healthy. We know this, in part, because mice brought up in a sterile environment reliably fail to develop normal, healthy immune systems.

These "friendly" microbes stimulate the immune system in many interesting ways. They train it in infancy and help to keep it finely tuned throughout life.

There is a further range of microscopic life that lives in our homes – on surfaces, on dust flakes and so on. Living alongside these familiar life forms is normal and healthy. Of course there are also occasional pathogens that can cause illness. But every day babies and toddlers get away with licking floors and other household surfaces without picking up diseases.

The report concludes that the hygiene hypothesis should be replaced by the "Old Friends" hypothesis. This states that allergies are on the increase because the mix of microbes on and around us bodies has changed. It is no longer the same rich brew that co-habited with our ancestors and is no longer quite what the developing immune system needs.  Our immune systems evolved alongside these old friends, developing  complex and subtle symbiotic partnership.

My grandmother grew up in the country, playing on the dung heaps in the yard, in a home that teemed with rural bacteria. When she had ear infections, the treatment was to pour her own urine into her ear. As her young immune system dealt with this environment, it learned to deal with a mix of bacteria that had probably changed little through the millennia.

My grandchildren, growing up in an urban environment, have encountered a different range of microbes. If you could analyse their microbe population it would not be smaller, but would certainly be different to that of their great, great grandmother. There will be an absence of some of the "old friends" that evolved alongside their ancestors for millennia.

It is not just an absence of dung heaps that has caused this change. It has become normal for children to have several courses of antibiotics for chest or ear infections. This will have affected their blend of gut bacteria. Hygienic caesarian birth probably has an effect and so might bottle-feeding from a sterilised teat instead of a mother's microbe-rich breast. Factors like this are probably far more significant than how often their parents clean the bathroom.

You may say this is not a revolutionary change of hypothesis, so does it matter? Should we worry about hygiene, and if so where and when?

Well yes, food and kitchen hygiene are important if we want to avoid food poisoning. Hand washing can reduce the number of “tummy bugs” and colds we contract. If someone in the family has a compromised immune system, then extra vigilance is needed. And if someone in the family is already asthmatic, then reducing house dust exposure might be helpful.

But we still have a lot to learn about friendly bacteria and intestinal parasites. We don’t know the identity of these old friends and whether it would be helpful to hold a reunion or not. It is a branch of science that is relatively new and is only just starting to yield interesting information. It will be a while before it comes up with any practical suggestions.

So if you were worried about your house being too clean, then you can indulge in a bit of anxiety-free cleaning. And if you were worried about a degree of household squalor, then worry no more. The friendly bacteria will carry on doing what they do, and cleaning, or not cleaning will probably have no effect whatsoever. 

To read more, here is a link to Science Daily

http://www.sciencedaily.com/releases/2012/10/121003082734.htm