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

Nature's best cold cure

It’s been years since I suffered from a “flu like illness”, years since I’ve had a cold at all in fact. But this week my luck has run out and I’m distracting myself by writing about the way the immune system reacts to viral infections.

As soon as a virus starts invading your respiratory membranes the innate division of your immune system detects the problem and swings into action. It produces chemicals known as cytokines that cause the symptoms we associate with a cold: mucus production, sneezing, stuffy nose and cough. Cytokines also affect your brain, making you feel lethargic. The body’s temperature control centre (also in the brain) may be affected, causing a  “temperature”. Inflammation is another feature of the innate immune system, hence the sore throat and pink eyes. It’s not the virus itself that causes all these effects – it’s the innate immune system reacting to it. In some viral diseases, such as pandemic flu, the immune system reaction can be so severe as to cause death.

While all this is going on and you’re struggling to carry on working, or flopped around apathetically watching daytime TV, the adaptive branch of the immune system is also working hard in the background. A swollen gland or lymph node can accompany this activity. A production line is being set up for B lymphocytes that will release antibodies against this particular virus along with a flood of uniquely-targeted T lymphocytes that will destroy the virus-infected cells. The process of getting this second-wave attack off the ground takes 4 - 7 days.

Sometimes the innate system does the trick and you “shake off the cold” quite quickly. On other occasions you just have to wait until the adaptive system is in full swing and has cleared the virus from your system.

Ibuprofen and paracetamol are helpful for relieving many of the symptoms. They are not cures however - nothing is, apart from the immune system itself.

Doctors call these viral infections “self-limiting illnesses”. Sit them out and your immune system will make you better. The body in this case is its own healer, rolling out an incredibly sophisticated dual-phase 100% successful cold cure.

In a few cases there are complications caused by bacteria which like to breed in the soggy, congested corners of the respiratory system. Babies and toddlers are more susceptible and chest infections are the most worrying. The immune system changes throughout life and as people move into their 60s and beyond they too also more likely to get a chest infection.

A bacterial chest infection that needs antibiotics is something more than just a cough. For symptoms, when to worry and other vulnerable groups see:

http://www.nhs.uk/conditions/Chest-infection-adult/Pages/Introduction.aspx 

http://www.nhs.uk/conditions/pregnancy-and-baby/pages/spotting-signs-serious-illness.aspx#close

The adaptive immune system remembers each virus it has encountered and will deal with it swiftly in future. However there are many viruses that can cause these annoying infections and because they keep mutating you will never, however long you live, be able to fend off every one.

The one I’m grappling with this week is rather persistent – but 5 days in now and I’m beginning to feel a slight lifting of the inertia that has consumed my week. I have, at least, finished writing this blog. But my patience is wearing thin, so do your stuff now, adaptive immune system, bring on those lymphocytes and bring me relief.

Scientists synthesise antibodies

This week scientists at Yale University have announced one of those game-changing achievements that could change the future of medicine. And, probably, win a Nobel prize. They have synthesized mini-antibodies that can function within the body and attack both cancer cells and disease-causing agents.

An antibody is a highly complex macro-molecule, produced by the adaptive division of the immune system. It’s a powerful bespoke weapon that will only attack a single type of bacterium, a particular strain of virus or a cancer cell with a particular genetic signature. They lock on to receptors on the surface of the pathogens and disable them. Imagine them as tiny wheel clamps that are individually designed for each new make of car that comes on the market. One of the problems with antibody production is that it is not instant. It takes the immune system several days or weeks to get its production line up to speed and in a serious disease like Ebola, the patient can die before enough antibodies are produced. Once the antibody template has been produced, it can be used more swiftly whenever the particular threat re-appears.To work on cancer cells the immune system first has to identify them as alien.

Antibodies are tiny and these new synthetic antibodies even smaller. Picture a bespoke wheel clamp on a jumbo jet. But that might make them easier to produce.

Currently there are just a few ways in which medicine can use antibodies:

Vaccines – in which the body is induced to create a new type of antibody without becoming ill. New vaccines are hard to develop.

Extracting antibodies from blood of those previously infected. This is being tried currently to treat Ebola.

Snake bite serum – produced by injecting animals with small amount of venom and then extracting antibodies from blood serum.

Monoclonal antibodies – producing an individual antibody type in the lab, using a complex biological system.

If simpler synthetic antibodies could be produced by a less laborious process than monoclonal antibodies it would open the door to a wide range of options in treating infectious diseases and cancers.

A ground breaking moment in immunology without a doubt.

http://bit.ly/13kPg4T

The immune system cleans up

The immune system is a teeming mass of interacting cells and complex organic chemicals that enable our bodies to deal with microbes. Immunologists have been toiling away for decades now and their research is, these days, at the level of individual molecular pathways. There are millions of these pathways – the circuit diagrams in an unimaginably complex computer.

One of the less well-known roles of the immune system is to identify and remove faulty, worn out or cancerous body cells. In other words it doesn't just fight off intruders, it declutters the house as well. It is fundamental to the immune system that it must, every day, make millions of judgements about what is ‘self’ and ‘not self’ so that it knows whether or not action is needed. It seems that cells that don’t pass its quality control process become re-classified as no-longer-self and dispatched for recycling.

Research into the molecular mechanisms of this decluttering process is beginning to lead to new medical treatments. 

In one recent report, a drug has been used (on a small group of patients) to block a molecule that enables bladder cancer cells to prevent an immune attack. The results are looking promising. The cancer cells disguise themselves as ‘self’ and the immune system ignores them. But the compound whips away the disguise and enables the malignant cells to be identified and destroyed. Treatments based on discoveries like this could eventually replace chemotherapy, which uses cytotoxic chemicals that inevitably damage healthy tissues.

http://bbc.in/1HQDMGv

In another study, a potential new treatment for malaria has been discovered and is ready to progress to safety trials in humans.

The malaria parasite makes its home inside healthy red blood cells. A couple of million red blood cells are produced every second by the bone marrow, so an equivalent number of worn out cells must be efficiently destroyed and removed from circulation. After detailed research into the genetics and cellular mechanisms of the parasite and into the way the immune system disposes of blood cells, a compound has been discovered that seems to hasten the disposal of malaria-infected cells and clear the parasite from the blood of mice. This is hopeful news when you consider the toll that malaria takes, particularly on young children.

http://bit.ly/1yovBcB

There is an enormous amount of fundamental research that has brought immunology to this point - mountains of Ph D theses and thousands of careers bent over the laboratory bench. This kind of research is not funded by drug companies and the fact that it is now, finally, beginning to produce treatments highlights the need to maintain public funding for pure science.

"Immune Boosting" Alcohol?

Everyone wants to promote the idea of “boosting the immune system” these days. Those who sell supplements lead the charge, with a regiment of alternative practitioners following closely behind. Immune boosting is also a favourite phrase with journalists, It’s a cheap and easy way of writing headlines. Scientists and science journalists succumb to its lure as well. This reported experiment with Barbary apes and alcohol is a good example.

Eight monkeys were allowed free access to alcoholic drinks for 7 months. Four of them were deemed heavy drinkers and the other four, moderate drinkers, depending on their freely chosen intake. There was a comparison group that was allowed no alcohol. The monkeys’ response to smallpox vaccine was tracked. It is not surprising that the heavy drinkers showed impaired immune function. Alcohol is toxic and large amounts of it will damage just about any bodily function you care to name.

What was more interesting is that the moderate drinkers had a better response to the vaccine than either of the other groups. We should, though, be skeptical about the size of the groups and the fact that the comparison groups were self-selecting rather than randomly allocated. Maybe the immune systems of those drawn to heavy drinking were different in some way to the more temperate beasts. We should also, always, be skeptical about making direct inferences from animal studies to human health.

For scientists, or science journalists, to talk about “boosting the immune system” is a bit like the mayor saying that some free-to-use bikes will boost the economy of the city, just because a few more energy drinks were sold in a few local kiosks. Like a city, the immune system is an immensely complex and intricate set of interlocking sub-systems. Millions upon millions of immune cells interact with billions of immune molecules to keep a body in a finely-balanced state of health. There are many different types of these cells and molecules - they are incredibly small and incredibly numerous. Strength of response to a single vaccine does not tell us anything about how the same immune system might cope with other vaccines, with TB, MRSA or the common cold. You cannot “boost” the whole thing – it’s a crazy concept. And we should never forget that an over-active immune system can be just as harmful as an under-active one – in allergies and the many auto-immune diseases for instance.

It’s New Year’s Eve – if you drink heavily you might be more likely to get an infection of some kind in the next few days. But if you exercise restraint and only have a glass or two, there are no promises that this will serve to actively improve your health. But drunk or sober, I hope you have a happy and healthy 2014.

Moderate Alcohol Consumption Boosts Body's Immune System

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