Why's my virus lingering?

In my previous post, written while in the gloomy grip of a viral illness I was eagerly awaiting the arrival of legions of lymphocytes and antibodies, all perfectly honed to deal with this particular virus. I am now at the “lingering” phase.

Disabling lassitude and gloom receded as my innate immune system retired from the field. My energy levels are nearly recovered but my sinuses are sensitive and my nasal passages and larynx are still decidedly damp.  And everyone I speak to who has had a winter virus seems to have the same complaint – it’s gone, in the main, but not yet forgotten. “It’s lingering” seems to be the common theme.

We should nod with respect to the complex interaction that helps us move into phase two. The innate system obviously “knows” when it can let up with those darn cytokines and let the adaptive system do its work. Hence the big leap forward after 4-7 days.

But why does the miraculous and ultimately effective adaptive immune system take so long to finally get rid of coughs and catarrh?

We have to imagine a numbers game. Viruses “breed” by invading cells and using material in those cells to make a new batch of viruses. The numbers produced are very, very large. Every time an infected cell bursts open they are releasing many thousands of virus particles with the potential to infect nearby cells.

The lymphocytes and antibodies are numerous too, but as they start to do their work, the virus production line is well-established so there is a massive amount of catching up to be done. It’s a bit like weeding a large patch of land on which the weeds are already producing seeds and the seedlings are sprouting almost as fast as the gardener can work. In the end the adaptive immune system always eliminates the last few viral particles. And the bonus prize is that it remembers the unique signature of the virus, so if you encounter it again next year it will be despatched without causing a single symptom.

I have just read a long and detailed account of the interaction between the immune system and the virus during flu (see link, below). As I sit here coughing I am slightly cheered by the thought that the sticky cough-inducing mucus in my larynx is the result of the wholesale death of infected cells.

This little episode has reminded me that influenza and other flu-like illnesses do nothing to enhance life. They can wipe out a week, or three while you wait for them to go. At least when it comes to influenza itself it’s easy to reduce the chances of picking it up by having a flu jab every autumn. It won’t prevent every possible virus – but it increases your chances of having a flu-free winter, and that’s worth having.
http://bit.ly/19yZ5jr

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

T Cell Therapy for Leukaemia - Why is this news?

In a recent report in The New England Journal of Medicine, the authors explain how two child patients were treated with a new technique. In both, their leukaemia was cleared and one of them remains in remission. The technique has previously had some success on a small group of adults.

News of medical research does not usually cover successes in just one or two patients - so why did the researchers go public on this?

In solid cancers you can never be sure that there are no cancer cells left in the body but in leukaemia you can be much more certain. It is no longer a case of looking at slides through a microscope - the latest techniques and equipment can scrutinise large numbers of blood cells and detect the presence - or absence - of cancerous cells.

There are many different kinds of leukaemia, each relating to a particular kind of blood cell. The nursery for blood cells is the red bone marrow and it is here that leukaemia cells are produced before they are released into the circulation. This red bone marrow is essential to life. It not only replaces red blood cells but all the white blood cells that make up the immune system. Without it, fatal anaemia and infection are inevitable.

Doctors can categorise the various leukaemias very accurately these days. For some patients the prognosis is good. For others, the only hope is a stem cell (bone marrow) transplant. These two young patients were suffering from relapsed Acute Lymphoblastic Leukaemia (ALL).

A stem cell transplant is usually the treatment of last resort. It uses brutal chemotherapy to kill all the red bone marrow, diseased and healthy. Then there is an infusion of blood stem cells, gathered from a closely matched donor. These then set up home in the bone marrow cavities and rebuild the blood producing tissue. It is a risky and arduous process. For some it fails to work and for others the treatment itself proves fatal.

Medical researchers sometimes use what they call translational research, which they also refer to as "bench to bedside research". Scientific advances in the lab are tried out on small groups of volunteers. These are patients who have little to lose - maybe a stem cell transplant has already failed - and they are willing to take the risk of acting as guinea pigs.

Translational research is quite different to a controlled trial - it is, literally, trying out something that they think should work to see what happens. This paper is an example of translational research - hence the tiny numbers. The progress of research like this is slow. Suitable patients are rare. By publishing this early success, researchers can share knowledge and perhaps find other patients who would benefit.

 We have long had the tantalising knowledge that immune cells known as T cells (or T lymphocytes) can destroy cancer cells in the lab - but often fail to do so in the body. One of the reasons for this failure is that the immune cells cannot recognise the cancer cells as something alien to the body. Store detectives deal with a similar problem: shoplifters tend to look like honest shoppers.

In the experimental treatment two child patients were treated with a kind of gene therapy in which T cells were genetically altered in the lab and put into the patient's body. The technique teaches the T cells the exact molecular pattern they need to attack and harnesses their killing power. It's like giving store detectives a photograph of a professional shoplifter.

There was a serious reaction to the treatment - the children's immune systems reacted violently to the rapid dying-off of cancer cells (tumour lysis syndrome). But both went into remission with no trace of the ALL cells. One of them subsequently started producing a slightly different kind of leukaemia cell but the other seemed to be remaining clear.

Such new forms of treatment may in time prove to be less dangerous and more effective than the current approach, which involves strong chemotherapy drugs. For sick children and their parents in particular, a shorter and less arduous course of treatment would be a great step forward.

Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia," New England Journal of Medicine, Online March 25, 2013. To appear in print April 18, 2013.

Science Daily article: http://bit.ly/ZoAuE6