Immunity

NK cells are our bodies’ main cancer-surveillance tool. With specialised receptors, they patrol the body inspecting each cell. They respond to newly formed tumours and abnormal growth of our own cells. And they also decide the fate of a pregnancy. NK cells represent 10 per cent of white blood cells but are also found dotted around the body in various places including the liver, lungs and lymph nodes – like your very own Special Forces regiment, with a smaller number of troops but just as deadly as an entire infantry division.

Really Tolerant T Cells

Military metaphors can be a useful way to describe our immune defences, but only when we use them in a nuanced way. The immune system is more sophisticated than a ruthless defender using brute force. It is, perhaps, more of a peacekeeping force, seeking a steady, harmonious state, not a constant battleground. Although it focuses on tossing out the bad guys, it must do this while causing as little damage as possible. This is to avoid damaging our precious tissues.

So who guards the guards? At the top of the peacekeeping chain are T regulatory cells, known as Tregs. Tregs control or suppress other cells in the immune system, fighting substantial fires and making sure the other cells toe the line. Tregs are designed to send a signal that immunity should withdraw, pause an attack and stand down.

Without these regulatory cells and molecules, the state of inflammation that helps destroy threats would lay our bodies to waste. Tregs are crucial to the overall balance of our immunity. They maintain tolerance to ‘good’ germs, prevent autoimmune diseases and limit inflammatory ones. But they can also suppress the immune system, preventing it from doing its job against certain infections and tumours. For optimal health, we require sufficient but not excessive regulation by Tregs. Imagine a small proportion of your immune system is reserved for regulation. Some of that is genetically determined, but some can be shaped by life choices like diet and exercise, stress and sleep. The system therefore operates on a constant tightrope: insufficient immunity (too many Tregs) may increase incidence of infections and cancer, while excessive ‘friendly fire’ (too few Tregs) may lead to damage to our own cells and organs.

Vaccination – The Great Teacher of Community Immunity

Vaccination is one of public health’s greatest success stories. Yet it also has become one of the most contentious areas of health policy over the past two decades and few things are more divisive in immunity than vaccinations (see Chapter 2 for more on this).

Vaccines work on the same principle as acquiring an infection naturally. When you acquire an infection naturally, your adaptive immunity, T cells, B cells and antibodies, are primed to fight off the germ. Then, a residual immunological memory remains, patrolling your body for decades (perhaps even a lifetime), ready to protect you if that germ ever tries to infect again. Your immune system reacts to the vaccine in a similar way to being invaded by the disease itself. Introducing a bit of weakened virus or bacteria teaches the immune system how to deal with it. It generates a memory response so when the real germ comes along, an army is at the ready. Just as each germ is unique, each vaccine is too. The memory produced by vaccines is different for each type. This is why some require booster shots – because vaccines don’t 100 per cent replicate the natural course of an infection, they (mostly, depending on the vaccine) don’t all provide the same degree of immunological memory.

Why Do Some People Never Seem to Get Sick?

In my job I like to practise what I preach. Most of the time I pretty much have my health nailed down, but each year I still catch the odd cold or bug. The average adult will get two to four colds a year, but some lucky people claim never to catch a cold or take a day off sick. We’ve all met them, whether it’s through family or at work – they breeze through cold and flu season without so much as a sniffle. What is their secret? How can we be more like them?

Your immunity is unique to you and determined by several factors. Genetics plays a part, but not in the way you might think. We each have around 25,000 genes, but your genetic code only differs by about 1 per cent from that of the person next to you. You might think that the majority of these differences are related to why we all look different, varying our hair colour, height or personality. But, aside from our brains, the genes that vary most between us are, in fact, a tiny cluster that plays a disproportionately large part in our health. This gene cluster is called the human leukocyte antigen (HLA), also known as the major histocompatibility complex (MHC). Let’s call these genes the ‘compatibility’ genes for short.

Our compatibility genes encode our immunity, yet they are as changeable as the pathogens (bacteria or viruses) they aim to prevent. These molecules have evolved to come in a variety of shapes and sizes. They mutate with each generation, unlike any other genes in our bodies, in an effort to track the ever-changing infectious threats we face. Our immunity depends on their combined performance. Our compatibility genes flag viruses and bacteria, and present them to the immune system for eradication. The fact they come in a range of shapes and sizes, prevents a virus or bacteria from mutating and then evading the immune system in every person they infect.

These special genes tell us a lot about the intricate balancing act essential for not only our health, but the survival of our species. Humans are incredibly similar but also fundamentally diverse, and compatibility genes are the key to our individuality. Simply put, if all our immune defence systems were identical, a single deadly disease could come along and wipe us all out. But this ingenious process comes with certain trade-offs. For example, we can’t easily exchange our body parts; if you have ever received an organ transplant, you will be familiar with the lifelong challenges involved in stopping your body rejecting the new tissue. In fact, immunity that works wonders for protecting one person can be quite deadly in the life of another.

Compatibility genes are the reason why we all fare differently when faced with the same infection. You may have inherited a set of compatibility genes that are expert at dealing with one particular virus – the common cold, say. This does not mean that your immune system is better or worse than mine; just that yours would deal better with fighting the seasonal lurgy. But when it comes to a different type of germ, I may fare better. And it’s not just our individual susceptibility to infection that is affected by our own unique combination of compatibility genes. For example, there are genetic variants in immune compatibility genes which protect some people from the HIV virus but leave them with an 80 per cent chance of getting a horrible autoimmune disease called ankylosing spondylitis.

Like our fingerprints, immunity makes us truly individual. The inherent diversity in how our immune systems respond to different diseases is an entirely deliberate design by mother nature without hierarchy. While the world is busy arguing over the physical, visible differences between people, our immune compatibility genes don’t discriminate. No one has a better or worse set. It’s the collective diversity that’s crucial. This diversity has been carefully crafted by evolution. Millions of years of evolution have more or less tuned our immune system to be running optimally. We might not be able to become completely resistant to disease, but it’s why we haven’t all been wiped out already.

Our immunity has been in place for around 500 million years. Its history goes so far back that we share it with other jawed vertebrates. And it has remained largely the same ever since it first evolved. Our immunity is millennia old, shaped and polished by evolution, and, by virtue of this, it is very good at what it does. The fact that our immune system is largely untouched by evolution is a testament to how important and effective it is and always has been. Evolution is not a predetermined design process; rather, it is one that advances in fits of trial and error as well as chance and necessity. Your successors will carry in them not only the final product of these efforts, a one-and-only perfect immune system, but also the marks and remnants of many immune systems.

If the Immune System Protects Us, Why Do We Still Get Sick?

Most of the time, our bodies win the fight against germs, but sometimes they lose. People who ‘never get sick’ may catch a slight cold now and again or suffer an occasional ache and pain. This makes sense when you realise that we live in a microbial world, and the microbes were here first.

Microbes haven’t only threatened our health, they have shaped it. They were the first traces of life to appear. And much later on, from within those early microbial ecosystems (and never separate from them), larger multicellular organisms evolved. Including us. And we have never quite separated from them.

Now we know that there are up to 1 trillion microbial species on Earth, and only a minute fraction of them cause disease. So vilifying all microbes for the sake of a few is a mistake, and possibly one of our biggest (you’ll discover why in Chapter 3). Nevertheless, much of the fear of microbes lingers in the public consciousness. As I mentioned, it’s quite normal to get up to four minor infections (like a cold) each year. But as infections are beaten back by modern-day sanitation, vaccination and antibiotics, we now have huge increases in ‘non-infectious’, lifestyle-related diseases. As you will read, this is no coincidence.

Let’s look at how infection spreads. Take rhinovirus, the cause of the common cold, for instance. Roughly one in five people carries the rhinovirus at any given time in the tissues of their nasal passages (the prefix ‘rhin’ in Greek literally means ‘the nose’). To infect you, these germs need three things:

 A way to get out of the reservoir (the person sitting near you who is sick)

 A mode of transportation to a new home (that person sneezing – a sneeze produces 40,000 droplets and you can get infected by inhaling just one)

 A way to get into their new home (you)

Another classic route for the spread of germs is poor hygiene, especially inadequate hand-washing. Bacteria are passed to everything we touch. But simply being a thorough hand-washer with good personal hygiene helps you stay healthy and avoid illness-causing bacteria. And while we can’t account for how infected people behave around us and we can’t control for the immunity genes that we have inherited, we do have some control over the various lifestyle levers we can pull to get the best out of our defences.

Nature Versus Nurture

Like fingerprints, immune systems vary from person to person. We all inherit a unique set of immunity genes – but this is just an instruction manual, and while the code can’t be changed it can be interpreted in many ways. You can help train and maintain it. Epigenetics (the study of how our genetic code is interpreted) is manipulated by many lifestyle factors. An example of epigenetics might be the changes in something called DNA methylation. (Essentially, methylation is like handcuffs for a gene, marking that gene as not to be used. If certain genes are methylated, then a cell might not be able to turn on critical functions and could become a cancer cell, for instance.) Various environmental factors can alter our methylation pattern, such as smoking, poor diet, air pollutants and alcohol. Adjustments in our epigenetic patterning can derail some of our vital immune responses. The metaphor used by scientists is: ‘Your genes load the gun, but environment pulls the trigger.’ Just a little immunity TLC from time to time can, for most people, keep all components functioning more smoothly.

Despite the prominent role played by genetics, immunity is not fixed by our genes. It’s continuously nurtured by our encounters and adventures, shaped by our changing emotions and surroundings, responding to how we live our lives.1 As mentioned, our immunity even has the capacity to learn and develop a memory. Collectively, this plethora of influences accrued across a lifetime determines, at any given point, if we get sick and for how long. This human ‘exposome’ is our immunobiography (more of which later), the culmination of everything that challenges our health throughout our lives, including infection, our diets, lifestyle factors and social influences. In short, it’s what we refer to as nurture (nature being the genetic part). This holistic view of health and disease goes some way to explain why some people end up being more susceptible to getting sick.

INFECTION – THE FACTS AND THE FICTION

It starts with a sniffle. Next thing you know, the whole household is sneezing, coughing and passing tissues. Before long, the common cold, or worse, the seasonal flu, is upon you all. Wondering how you can dodge those germs or ‘boost’ your immunity? With so much conflicting advice out there, it can be difficult to know what to believe. So let’s start by putting myths to rest with a simple guide.

No. 1 Tip to Avoid Infection

In the mid-19th century, a Hungarian man called Dr Ignaz Semmelweis made an important discovery. He linked childbed fever among women who had just delivered their babies in the hospital to the failure of the doctors who delivered those babies to wash their hands after performing anatomical dissections of the dead. The key to reducing infection was simple: wash your hands. Semmelweis died before his theory gained support, but hand-washing remains a cornerstone of modern-day infection control.

Most People are Infectious Before They Get Symptoms

Before the onset of symptoms, a person may already have an infection. How this works depends on the germ in question. Respiratory viruses are best engineered to spread when you have physical symptoms; the more symptomatic you are, the more you sneeze and cough, the more likely you are to spread an infection. But sometimes you can infect others with a virus even when you are asymptomatic. For influenza, you are infectious one day before symptoms and five to seven days after their onset. Young children and patients with altered immune systems can spread the virus for longer periods of time.

It’s Just a Mild Cold – Am I Less Infectious?

Just because you have mild symptoms doesn’t mean the virus is mild. It may just mean that you lucked out with your compatibility genes for that particular germ and your immune system is able to control the infection. For this reason, it’s important to remember that even with minimal symptoms, you can still infect others and potentially make some people really sick, especially those who are vulnerable, including the elderly and very young.

Why Do Colds and Flu Strike in Winter?

The flu season in the UK starts in October and is in full swing by December, generally reaching its peak in February and ending in March. For our Antipodean cousins, the season is flipped. Put simply, whenever and wherever there is winter, there is flu. Even the word ‘influenza’ may be a clue – its original Italian name, ‘influenza di freddo’, means ‘influence of the cold’.

A common misconception, however, is that flu is caused by cold temperatures. This is not quite true. Flu is caused by the influenza virus. Cold temperatures simply create conditions that make it easier for the virus to spread. Scientists now know that the influenza virus is transmitted best at cooler temperatures and low humidity. So the viruses that cause the flu survive better in winter and are able to infect more people. Another reason is the lack of sunlight and the different lifestyles we lead in winter months: days are colder and shorter during the winter, so we spend more time indoors and are more likely to share air with someone who’s infected. Lack of sunlight leads to low levels of vitamin D, a key immune-nourishing nutrient. Having less vitamin D decreases our immunity’s ability to fight the virus.2

You’ll Catch a Cold from Being Cold

‘Put on a jacket or you’ll catch a cold.’ I’m sure you were told this as a child, but nowadays it is usually dismissed as an age-old misconception. Much like the previous point, it’s the virus, not the temperature, that makes us sick, right? Well, yes. But it turns out that this advice contains a kernel of truth too. It has been shown that when you are exposed to the cold for a prolonged time you may not be able to launch the most robust immune attack. While this effect might be marginal in most healthy people, older people, young kids or those with underlying health issues may have an even harder time fighting off the virus. So, best heed your parents’ advice and bundle up when heading out in the cold! Wearing a scarf in winter does warm the air in the back of your throat, making it less hospitable for those seasonal viruses that prefer cool air.

Disease Symptoms Are Sometimes the Immune System Doing Its Job

You might have heard that bacteria, viruses and fungi are the cause of disease symptoms, but often this is technically incorrect. Disease symptoms mostly occur because your immune system is at work reacting to trespassing micro-organisms with inflammation.

Take the example of the common cold. Your immune system jumps into action when the cold virus (rhinovirus) invades the epithelial cells that line your airways. Immune system chemicals dilate your blood vessels and increase their permeability, allowing proteins and white blood cells to reach the infected tissues in your nose, sinuses and throat. However, this causes nasal congestion. Additionally, you may get a runny nose because of the increased fluid leakage from your permeable capillaries, combined with increased mucus production triggered by the immune response itself. Then there is fever.

Through evolution, we developed fever as a response to infection. Raising your temperature makes most germs less efficient at multiplying and helps your immune cells work more effectively. There is evidence too that fever even improves the ability of antibiotics to kill bacteria.3 Awareness of this phenomenon has given rise to two appealing, but conflicting, schools of thought. One theory is that fever is a natural part of the immune response to infection, so we shouldn’t interfere with it. The other is that fever is a potentially harmful consequence of infection, so we should suppress it to minimise any complications.

What does science have to say about these conflicting theories? There is actually little evidence that fever itself, even a high one, is harmful.4 Unless you are really uncomfortable, have difficulty breathing or have a fever lasting more than a few days it’s normally wise to avoid fever-reducing medications like paracetamol or ibuprofen as they are not without side effects. The immune system can still get its job done if you take medicine to reduce fever, but slightly less effectively – and taking it won’t speed up the process.

Over the Counter

No one wants to stay at home feeling miserable with a cold or the flu. And sometimes you just can’t. So what about all those over-the-counter (OTC) cold and flu medications? Most OTC cough syrups are not effective for adults or children,5 and the NHS now recommends honey rather than cough syrup. OTC cold and flu medications won’t ‘cure’ or even shorten your cold or flu, but there is some evidence that they may provide some symptom relief in adults. Each time my husband catches a cold, he treks to the pharmacy, spending (wasting) lots of money searching out a cure. Perhaps the idea that he is proactively looking after himself makes him feel better about the situation, which may create a little placebo effect. But the pills he buys won’t cure his cold.

Reducing symptoms is, however, often desirable, or necessary if life demands that you function. So if work really can’t wait, which product is best for your symptoms? Here’s the lowdown:

Antibiotics definitely don’t help and shouldn’t be used for the viruses that cause colds and flu. Cold and flu tablets may contain decongestants, pain relievers, antihistamines and cough suppressants. So think carefully about your main symptoms when selecting a product and read the label carefully – avoiding taking medicine you don’t need reduces the risk of side effects. Decongestant tablets can have effects beyond the nose and may exacerbate other medical conditions such as high blood pressure. Speak to your pharmacist before taking these medicines.

When it comes to immunity there are few quick fixes. The minor benefits from certain treatments need to be weighed up against the risk of side effects and the cost of the medicine. There are a few nourishing ways to ease a cold without pharmaceuticals but rest really is the best medicine. If only you can step off the treadmill of life for long enough.

DO YOU NEED AN IMMUNE ‘BOOST’?

If a well-functioning immune system is key to living a longer and healthier life, then the idea that you can boost your immune system is certainly enticing. Searching ‘immunity’ online or walking through the aisles of any health-food store reveals an abundance of nutritional supplements, cold remedies and fortified foods all promising to ‘boost’ your immune system and, by doing so, to stave off colds and flu. But is there any scientific truth in these claims?

Sadly for consumers of these ‘immune-boosting’ products, the notion of the immune system as some kind of internal force field that can be easily ramped up makes little sense scientifically and is one of the biggest misconceptions about immunity that I come across in my work.

Because of the way your immune system is designed to work, you definitely wouldn’t want it to be boosted. Taken literally, the term ‘immune-boosting’ is an unfortunate one. Rather than a single binary on/off switch, the immune system is more like a series of switches – a rheostat requiring constant tweaking to get it just right. Attempting to ‘boost’ the cells of your immune system is complicated. There are so many different kinds that respond to so many different microbes in so many ways. Which should you boost? And how much? So far, there is no single answer.

Researchers have looked at whether things like echinacea, green tea, garlic and wheatgrass supplements can help us see off germs, but existing evidence in support of a single immune-boosting nutrient or superfood is not strong. If you are looking to strengthen your immunity, the best way is through a combined approach based on the information in the following chapters’.

NOT ALL GERMS CAUSE INFECTION AND NOT ALL DISEASE IS FROM GERMS

Not all germs are bad and not all disease is caused by germs. Although germ theory still dominates how we think about immunity, we know that things are more complicated than that.

The Danger Theory of Disease

It would be nice to have a simple, clean separation: immunity doesn’t react to our own harmless ‘self’ molecules, but only to things that are not us – i.e. harmful ‘non-self’ germs. But is this the case? Are all harmful, non-self, immune-triggering molecules from infectious germs? To complicate matters further, not all diseases are caused by foreign germs (take allergies, for example). And not all germs in the body warrant destruction (the microbiota say, that you will meet in Chapter 3). Various aspects of our day-to-day lives involve interaction with something non-self – and many are things that we don’t want our immune systems to reject: mothers don’t reject foetuses; we tend not to attack the food we eat; and we don’t reject the millions of microbes living harmlessly, and often helpfully, on and in us. All these are examples of foreign ‘non-self’ things that somehow evade the immune system’s wrath. Yet non-infectious immune diseases related to modern lifestyles are rampant. Until relatively recently the field of immunology was agnostic as to how this happened. Then, along came Polly.

While for decades we wrongly assumed that the immune system could simply spot self and differentiate that from non-self, a 20th-century immunologist rewrote the script. Born in 1947, Polly Matzinger blazed an unconventional trail. Following stints as a bass player, a dog trainer, a carpenter, a biology student – and later a Playboy bunny – she went on to change our understanding of how disease happens, poking holes in the dogma and becoming one of the most influential thinkers in the field. It turns out that immunity is not just concerned with whether the thing it is reacting to is self or non-self; rather, it is also hard-wired to detect patterns of danger.6 Why is danger relevant? We can get sick in the absence of an active ‘non-self’ infection. Which means that something is still triggering the immune system when germs are absent. This trigger, Polly discovered, is a pattern of danger signals from our own cells and tissues.