Ebola and the immune system

I’ve often wished the immune system had a different name. One that sounded a lot more grand and complicated. It slips easily off the tongue and gulls people into thinking that it’s no more complicated than their central heating system. And that the equivalent of a tweak of the thermostat (in the form of a pill or a foot massage) can give “it” a quick boost. When researching my book I realised that it’s a system of a very different kind – more like, say, the complexity of a city like London with its workers, businesses, buildings and transport networks.

There are two main divisions to the immune system. The emergency “innate” division kicks in the minute you have a wound. On a much slower timescale the “adaptive” division learns about all the bacteria, viruses and proteins in your environment – which to ignore and which to attack with antibodies the next time they crop up. There are many different types of immune cell (“white blood cells”) and new sub-types are discovered regularly. They produce a vast array of complex proteins called cytokines that also play a role in attacking pathogens. Part of what we mean by “immune system” is this interacting mass of cells and proteins that flow through blood and tissues during health and illness. But there is more. The permanent structures of the immune system are the bone marrow, which is the production unit for replacement immune cells, and the lymphatic system that monitors threats throughout the body.

As in cities, balance is important. You don’t need a rail system that varies its timetable unpredictably. Neither do you need an immune system that is over- or under-active. Everything has to be modulated to keep things running smoothly so as to prevent not only infection but also self-damage. Diseases associated with an over-active immune system include all the auto-immune diseases, allergies and inflammatory conditions. Toxic shock, sepsis and the cytokine storm (which can occur in pandemic flu) are more sudden and much more deadly over-reactions.

Some illnesses are not just attacked by the immune system – they directly infect immune cells and interact with them in complex ways. It’s well known that the HIV retro-virus directly attacks immune cells, using them as a base and slowly undermining their work. TB, caused by a bacterium, also infects immune cells – the ones that normally engulf and destroy bacteria entering the lungs. Ebola too infects immune cells, and progresses far more swiftly than HIV or TB. It does so by using infected immune cells to spread the virus throughout the body. Ebola is also able to damp down aspects of the immune function. But that is not all. The high fever and inflammation of the later stages of the disease are part of a massive immune over-reaction that contributes to death. 

There are various scientific initiatives attempting to tackle this unusual virus but the solutions are not simple.

There are some anti-viral drugs undergoing accelerated trials but it would be surprising if they make a significant impact. The might of the pharmaceutical industry has yet to produce a range of wonder-working anti-virals for other diseases. Anti-retrovirals, used for HIV, are probably the biggest success, despite all their limitations. Vaccine development is a long and difficult road and vaccines in current development are a while away from any prospect of a  mass roll-out. The experimental biological treatment ZMapp is a product of immunological research. It’s a combination of artificially produced antibodies that lock on to specific targets on the Ebola virus, disabling it. It is to be hoped that ZMapp works, and that one day it can be produced in large enough quantities to be useful in bringing outbreaks under control. However production methods are complex involving a lot of careful work by technicians and the growth of cloned cells in laboratory conditions. This process is not at all like the factory production line that produces conventional chemical drugs. My feeling is that science is very unlikely to come up with any quick answers, with mass impact, in the next few months.

In the meantime though, simple nursing measures like infection control and putting up a drip can save lives. As Christmas looms we are asked to contribute to a wide range of charities but this year many of us will perhaps consider that paying for some nursing supplies for Ebola stricken areas is the most urgent call on our generosity.

http://www.bbc.co.uk/news/health-30217573

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

Undercover Inflammation?

There is increasing mention of the word inflammation these days - in relation to diabetes for instance. Put the word into Google and you get 66 million hits. Many of them will be talking in alarmist terms, claiming that inflammation causes nearly every worrying disease you can think of. They go on to recommend anti-inflammatory diets or supplements. It's a typical sales pitch: create concern; convince customers they have a need and then offer a solution.

But scientists also seem interested in chronic inflammation, so what is behind this increasing interest?

Inflammation is the emergency response of the immune system. If you scratch your hand in the garden, within 24 hours it will be red and swollen. Around the scratch, tissues are flooded with fluid. This contains a potent mix of immune chemicals whose main role is to disable bacteria by attaching themselves, in a kind of chemical rugby tackle. They will also send out an alarm call to millions of immune cells (white blood cells). When they arrive on site they destroy the immobilised bacteria. Within a couple of days the redness and swelling is subsiding and the inflammation starts to disappear as the immune system stands down. Inflammation is nature's way of protecting the body against bacterial invasion and it saves lives on a routine basis.

The problem comes when there is inflammation without any invading bacteria.

Unwanted inflammation can cause damage to healthy tissues. In the absence of an enemy, the troops (the immune cells and chemicals) start picking a fight with the civilians. A vivid demonstration of this is seen in rheumatoid arthritis in which inflammation gradually causes permanent damage to a joint. 

Recent research has been unpicking the complex links between obesity and raised levels of inflammation chemicals in the body. These chemicals are referred to a “inflammatory markers” in research papers.

When someone gains weight, they don’t grow more fat cells. Instead, their fat cells store more and more fat, like balloons filling with water. When they get to a certain size they start to trigger tiny amounts of inflammation. This may be because they start to leak, or start interacting with immune cells in abnormal ways. Recent research has revealed that they can even start behaving a bit like immune cells when they become over-filled with fat. The net result is that there are more inflammation-related chemicals sloshing around the body than you would want. These chemicals can cause slow and subtle damage to tissues and play their part in chronic diseases. They are a link in the chain between increased body fat and the increased risk of heart disease and diabetes.

There is lots of research going on into the exact mechanisms. This is fascinating for those involved but the immune system is unimaginably complicated and therefore difficult to tweak. Science is unlikely to come up with any miraculous, seise-effect-free drugs that will protect obese people from diabetes and heart disease.

If you are overweight and concerned about your health then pills and potions will not “reduce inflammation”. They will just waste your money and make supplement sellers rich. The solution, I'm afraid is to eat a better diet, lose weight and shrink those fat cells.

"Obesity makes fat cells act like they’re infected." Science Daily article.

http://bit.ly/10aMgRR