Sunday, 1 July 2018

New Scientist: Immune Retune.

Immune Retune - Jessica Hamzelou,  New Scientist 03 April 2012 

"ACHOO!" A sniffling friend is sneezing just inches away. You would love to cover your face or run away, but in the interests of politeness all you can do is try not to inhale in their direction and hope your immune system is on the case.
Some people seem to catch everything that is doing the rounds, from coughs and colds to stomach bugs. Other people never seem to get ill. What's their secret?
A lot is down to dumb luck. There are some things affecting the performance of your immune system that you cannot change: your age, your gender, your genes, and most importantly, whether or not you have had a previous brush with an invading bug.
But there are plenty of factors you can control. I'm not talking about downing supplements sold as "immune boosters"; the claims for most such pills are not based on hard evidence. But there are plenty of other ways you can keep your immune system revved up and raring to go.
It's not all about boosting activity, though. Many common conditions are caused by the immune system reacting to things it shouldn't. When it attacks parts of the body the result is autoimmune disorders like multiple sclerosis, type 1 diabetes and inflammatory bowel disease. When it responds to molecules that are foreign but harmless, like those from pollen or peanuts, the result is asthma, eczema or allergies. Again, there are ways of encouraging your immune system to behave. So help it out by following these tips.
From an old-fashioned faith in the healing powers of chicken soup to more modern obsessions with so-called superfoods, we like to think some things we eat can help ward off infections. The vast majority of these beliefs have little evidence to back them up, but there are dietary interventions that appear to work.
Numerous supplements are sold on the basis of supposed immune-boosting powers, but their health claims usually stem from tests done on cells in the lab. That is just the first stage of gathering evidence, though; the only way to know for sure if something will work is a randomised, controlled trial done on people, preferably several trials.
By that measure, zinc supplements probably come out best, with evidence they can both prevent colds and shorten their duration if started within 24 hours of the symptoms first appearing (Cochrane Database of Systematic Reviews, DOI: 10.1002/14651858.CD001364.pub3). Zinc may work by stopping the cold virus from replicating or preventing it from gaining entry to cells lining the airways.
That old favourite vitamin C doesn't seem to prevent colds, although as a treatment it might reduce symptoms slightly. The only other supplement with any credibility is echinacea, an extract of the purple coneflower - although again only as treatment, not prevention, and even then the evidence is mixed.
Vitamin C boosts immune cell activity in theory so why does it perform so poorly in practice? It seems that while vitamin supplements help people who are malnourished avoid diseases caused by vitamin deficiency, such as scurvy, there is no extra benefit to exceeding the recommended levels, which most people in the west hit anyway. In fact, popping vitamin pills - including vitamin C - may even be harmful overall (New Scientist, 5 August 2006, p 40).
If you really want to support your immune system the best approach is simply to eat a plentiful supply of fruit and vegetables. They contain not just vitamins but thousands of other compounds called phytochemicals, which have numerous beneficial effects we are only just starting to understand.
It is also important to focus on the quantity of food, not just its quality. People who are obese are more likely to get a range of infections, including respiratory, skin and urinary ones (The Lancet Infectious Diseases, vol 6, p 438). Piling on the pounds not only makes it harder to breathe, which predisposes people to colds and flu, but the excess fat releases chemical signals that interfere with immune functioning.
Think carefully about how you shed the pounds, though, because yo-yo dieting is also harmful. Frequent cycles of weight loss and regain seem to reduce the performance of natural killer cells, an important branch of the immune system that targets cancerous cells and those infected with viruses (Journal of the American Dietetic Association, vol 104, p 903).
The human gut is riddled with bacteria. That is a good thing - as well as helping you to digest food, these friendly bugs are essential for a healthy immune system.
The gut flora, as it is known, competes with harmful microbes for nutrients and physical space. It also releases antimicrobial compounds and communicates with the immune system in complex ways that we are only just starting to unravel.
Given all this, it is not surprising that damaging your gut flora can leave you prone to bacterial infections. That's why when you take antibiotics for one infection, you are sometimes hit by another; the friendly bacteria are collateral damage. The superbug Clostridium difficile, for example, often strikes hospital patients after a round of antibiotics and is arguably just as big a medical headache as antibiotic-resistant species such as MRSA.
Instead of nuking your friendly bacteria you should nurture them. That is the aim of probiotics, daily yogurt drinks designed to boost the number of goodguys. After initial doubts that this approach would deliver enough microbes to do anything useful, studies now support the idea that probiotics can help treat gut infections, including diarrhoea associated with C. difficile, and even ward off coughs and colds (Cochrane Database of Systematic ReviewsDOI: 10.1002/14651858.CD006895.pub2).
As well as probiotics there are prebiotics. The idea here is to feed up your existing friendly bacteria with certain nutrients, often forms of soluble fibre. In one study, people in hospital who took prebiotics were less likely to succumb to further bouts of C. difficile infection (Clinical Gastroenterology and Hepatology, vol 3, p 442).
For people whose gut flora is beyond help, there is another option: a faecal transplant. Unappealing as it sounds, transferring someone else's faeces into a bowel severely infected with C. difficile has produced some striking successes. This is one immune booster, however, that you won't consider unless you are seriously unwell.
Close your eyes. Count to 10. Whatever you do, stay calm. Stress can weaken the immune system transiently but significantly.
Despite its New-Age associations, studying the links between mind and body is now a respectable field of research, sometimes termed "psychoneuroimmunology". Some of the classic studies have looked at immune responses after getting a vaccine. For instance, one of the pioneers in this field, Ronald Glaser at Ohio State University in Columbus, showed that people stressed out by looking after a relative with Alzheimer's disease had worse antibody and T-cell responses to a flu vaccine. Their wounds were slower to heal, and they also caught more throat infections (Annals of the New York Academy of Sciences, vol 840, p 649).
While there are myriads of signalling pathways between the brain and the immune system, the key players seem to be the stress hormones cortisol and noradrenalin. These bind to receptors on immune cells and interfere with their ability to respond to antigens, leaving us more susceptible to infections.
On the other hand a little of the bad stuff might be beneficial. A recent analysis of over 300 studies found that a short stressful experience, like public speaking, boosted blood levels of immune cells (Psychological Bulletin, vol 130, p 601). "A slight elevation of stress hormones is good for you," says Bruce Rabin at the University of Pittsburgh in Pennsylvania.
He doesn't recommend setting out to get stressed, but instead advises learning how to cope better with any stress that comes along. "Be optimistic,fit, have a sense of humour," he suggests. Most important of all is to keep your friends. "Loneliness is the killer."
This could be why women cope with bereavement better than men. "Women have friends that they talk to about personal issues," says Rabin. "It's a buffer."
How much shut-eye did you get last night? Even a moderate lack of sleep can put you at greater risk of catching a bug. In a seminal study, the sleeping habits of 153 healthy adults were recorded before they were given a sniff of a cold virus. It turned out that people who slept for less than 7 hours a night were almost three times as likely to catch a cold as the rest of the group (Archives of Internal Medicine, vol 169, p 62). It suggests people should make sure they are well rested before getting vaccinated, says Mark Opp, a neurobiologist at the University of Washington.
Opp recommends at least 8 hours and 20 minutes a night. That sounds a lot, but he reckons it is what everybody would get if left to their own devices. "If you take healthy subjects and let them sleep as long as they like, they sleep a little more each night, until it levels off at this duration," he says.
Sleep quality is also important, and that means making sure you are snoozing in a cool, dark and quiet place, says Opp. Living near a noisy place such as a train station is no good, even if you think you are used to the clatter. "People will say they're accustomed to the noise, but studies show that their sleep has been disturbed," says Opp. "If I put electrodes on their head, the brain activity would change to an awake pattern every time a train went by."
Having a healthy immune system isn't all about cranking up the dial to maximum. There is a large class of conditions caused by immune cells attacking things they should leave in peace - namely the body itself. Known as autoimmune disorders, the list includes type 1 diabetes, inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis.
These conditions have been linked to a lack of vitamin D - the so-called sunshine vitamin. Some foods such as dairy products and fish contain vitamin D but most is made in the skin when it is exposed to the sun's ultraviolet rays.
Vitamin D appears to play a key role in keeping the immune system in check so that it doesn't react to things inappropriately. The first clue that this was the case was the higher rate of autoimmune disorders in parts of the world with less sunlight. Since then, researchers have found that vitamin D suppresses the immune system by inhibiting the proliferation of immune cells and the signalling factors that spur them into action. The compound is even being investigated as a way of stopping people rejecting organ transplants.
Sunshine's effects stretch beyond those of vitamin D. Melatonin - a hormone secreted by a gland in the brain in response to changes in light - stimulates certain kinds of immune cells.
Vitamin D is also vital for calcium absorption and bone health. Unfortunately, growing awareness of the risks of skin cancer has led some people to shun the sun, hence a recent resurgence in childhood rickets.
Skin cancer aside, vitamin D appears to protect against many other common types of cancer, including those of the breast, prostate and colon. One research group has calculated that in the US, more people die from internal cancers caused by lack of sun exposure than from skin cancer itself - possibly four times as many (New Scientist, 9 August 2003, p 30).
So how much time should you spend in the sun? Michael Holick, a vitamin D researcher at Boston University in Massachusetts, reckons you should expose your hands, arms and face for a quarter of the time it would take to cause reddening two to three times a week.
Dermatologists tend to argue in favour of taking supplements instead, but multivitamin pills may not provide a high enough dose.
It can be hard to motivate yourself to exercise, but now there is yet another reason to do so: even short bursts of exercise give your immune system a temporary boost.
When 500 adults were tracked for 12 weeks, those who were the most physically active - five sessions or more of aerobic exercise a week - spent nearly half the number of days sick with an upper respiratory tract infection such as a cold or tonsillitis (British Journal of Sports Medicine, vol 45, p 987).
As your heart gets pumping, immune cells usually stuck in the blood vessel walls are washed into the circulation where they can do their stuff, says Mike Gleeson, an immunologist at Loughborough University in the UK. Levels of these cells in the blood double during exercise, upping the immune system's ability to respond to pathogens, says Gleeson. "Exercise increases immunosurveillance."It is possible to overdo it, but you would have to be extremely dedicated. Last year, Gleeson's team looked at how many colds athletes got compared with people who just kept fit in the conventional sense. Those who trained for 11 hours or more a week got more infections than those who worked out for between 3 and 6 hours per week (Scandinavian Journal of Medicine and Science in Sports, DOI: 10.1111/j.1600-0838.2011.01422.x).
Too much exercise has a similar effect to stress, raising levels of stress hormones such as cortisol that alter the functioning of immune cells (see "Take a deep breath"). "Even though there's an increase in cells, their function is depressed," says Gleeson.
He recommends exercising little and often, for no more than 2 hours at a stretch: "Restrict yourself to moderate exercise such as jogging or swimming."
What better way to engineer the perfect immune system than to start from scratch? While you can't do that for yourself, you can with your children. In the womb, babies automatically share their mother's antibodies, which cross the placenta. This antibody donation can continue after birth through breastfeeding.
Breast milk is chock-full of immune-boosting ingredients. There is lactoferrin, for instance - a protein that inhibits the growth of bacteria - and sugars that block bacteria from binding to the body's cells. Breastfeeding reduces infection rates, particularly in the developing world.
There is another way of furnishing a child's immune system with first-class defences that is quick, relatively cheap and arguably one of medicine's greatest achievements: vaccination against a dozen or more fatal diseases, available at a clinic near you.
Unfortunately, some anti-vaccine campaigners claim this amounts to "overloading" the immune system - an idea that has no basis in fact considering the millions of microbes we face down in every speck of dirt. The few antigens within a vaccine, even multiple vaccines given at once, are a hardly appreciable added burden, according to the World Health Organization.
Some childhood diseases, though, are caused by immune defences going into overdrive, including asthma, eczema and allergies to pollen or foods. We know that children are less likely to get such allergic conditions if they grow up on farms or have pets, lots of siblings or spend time in daycare.
Like most parts of the body, the immune system weakens with age. That is why older people catch more infections, are more likely to get cancer, and are more prone to shingles, a painful rash caused by the chicken pox virus reactivating after lying dormant for years.
You can't stop yourself from growing older but that doesn't mean you have to just sit there and take it. At the moment the only option is to take a leaf out of the kids' book and get fully vaccinated. As well as annual flu shots, older people can get a one-off vaccine for pneumococcal disease, which causes pneumonia and meningitis, and the "childhood" jab against diphtheria, tetanus and pertussis. A vaccine giving partial protection against shingles has also recently been developed.
In future there may be more high-tech countermeasures, such as rejuvenating the thymus - a gland in the chest where an important class of immune cells called T-cells mature. From puberty onwards the thymus gradually shrinks and is taken over by fat, and then it is downhill all the way.
There may be ways to reverse this decline, though. One candidate is injections with growth hormone, which has shown promise in people whose immune system has been depleted by AIDS.
Visible ageing is also seen at the cellular level. Every time immune cells multiply in response to a bug they recognise, parts of their chromosomes called telomeres shorten until there are none left. At this point they lose the ability to divide and become useless. As people age, more and more of their circulating immune cells approach the end of their lifespan.
This is unavoidable, but there is one microbe it might be particularly helpful to steer clear of: cytomegalovirus (CMV). Most people have a long-standing dormant infection with CMV which reawakens every so often, perhaps due to stress. This causes unusually widespread activation of immune cells, so hastening their decline. One theory is that CMV plays a key role in immune ageing. If that's true, then there is good news - a vaccine against CMV is on the cards (The Lancet, vol 377, p 1256).
Jessica Hamzelou is a science writer based in London