Immunity

In fact, we even have a term for this: danger-associated molecular patterns (DAMPs).7 Danger comes from any change in our cells and tissues, such as damage or stress, and can even be from lifestyle-associated molecular patterns (LAMPs).8 The immune system’s smoke detectors sense something is awry. This triggers a series of molecular signals which bring about an immune response. One example of how this happens is when inflammation occurs in the absence of any germs.9 We call this sterile inflammation. You might have experienced this, as I did recently after tearing the ligaments in my ankle. No broken skin and no infection, but immediate swelling and visible inflammation as my painful ankle ballooned and bruised. The missing ‘danger’ link in this situation is in part due to the mitochondria in our cells. The sheer mechanical tearing up of tissues (like when I twisted my ankle) releases the contents of our cells into the blood, including their cellular battery packs, the mitochondria, which are distant cousins of bacteria. In terms of our immunity, this means they are molecularly ‘non-self’, despite being part of us. Why is this important? Well, inside our cells, mitochondria are shielded from our immunity, but when they leak out, they are recognised (by innate immunity) as patterns of danger. Their bacteria ancestry makes them exceptionally good at signalling to start inflammation, even though no infectious germs are present.

Sixth Sense: Immunity Beyond Infection Protection

Understanding infection protection was the first step in discovering how the immune system works, and it remains the main lens through which our immunity is viewed. But infection protection is only part of the story. Vigilantly patrolling, our health guardian is always on. Beyond just surveying for possible infections, immunity has many additional vital functions: it governs repair and healing, regulates body weight and metabolism, defines how we age and if, or when, we might encounter age-related disease. Immunity also determines the success of a pregnancy or a transplanted organ. And, crucially, using those NK immune cells you met earlier, it is our main cancer surveillance system. The immune system is so fundamental to our existence, it’s the essence of our species.

People often talk about having a ‘sixth sense’, a way of perceiving the world other than by the standard channels of seeing, smelling, tasting, hearing or touching. I’d like to propose that your body has such a sense: the humble and hard-working immune system deserves recognition as a sensory organ of sorts. Much like vision, hearing and touch, our immune system recognises challenges from our environment and signals from our emotions. Unlike other types of cells, immune cells can sense and respond to environmental, hormonal, nutrient and even brain signals. This dynamic ability makes the immune system both fairly unique and quite peculiar.

In fact, science has started to consider immunity as a kind of second brain: a specialised network of biosensors designed to pick up information from within and around the body and relay it to the brain, where it can motivate and manipulate us to behave in specific ways. This may be as simple as huddling, shivering or sleeping – actions that are typically considered general symptoms of illness or debilitation, but may, in fact, be highly specific and beneficial responses to infection. In other cases, the immune system may inspire behaviours not typically associated with illness at all, such as passivity, aggression or sexual attraction. The immune system, it would appear, has quite a bit to say not only about how we behave but about how we feel and even who we are.

Instead of recognising light, sound waves or taste, the immune system recognises molecular shapes of germs, damage or danger – perturbations to our status quo. Sampling the environment, immunity has evolved rigorous mechanisms enmeshed with all our other body signals to keep us well. No other system in the body places such a premium on adaptability (except, possibly, the brain – and why would nature disconnect two such vital systems from one another?). If our immune systems can’t counter the diversity in our ever-changing environment by adapting and responding, we’re dead ducks.

Although it may sound counterintuitive, immunity keeps you alive, but is also disease-causing. Tip it one way, and your immune system weakens, leaving you vulnerable to pathogens. Tip it the other way, and it becomes overactive, attacking your own healthy tissue or benign things in the environment. Or it becomes unable to regulate the daily inflammatory wear and tear. These are not things you want.

Modern Malaise

Illness is part of our natural history – a biological heritage, crafted by evolution, the greatest part of it prior to the antibiotic era. Pre-antibiotics, infectious disease had the potential to wipe out the majority of us. This created evolutionary pressure to mount strong immune responses. But now, mostly everyone in the Western world survives the childhood infections of times gone by. As we humans have evolved, so too have our diseases. Over the past hundred or so years, deaths related to infectious disease have been dramatically reduced. But the diseases that have challenged us have also shaped us and left us with deeply embedded evolutionary vulnerabilities. And while epidemics of diphtheria, plague, cholera and smallpox no longer sweep across the Western world, we now have other foes to fight.

Today, germs are no longer the enemy. In fact, 99 per cent of those that surround us at any given moment (and they are everywhere, all the time) do not cause disease. Rather, they are ‘good’ bacteria – our microscopic health allies. This pokes holes in the ‘all-germs-are-bad-and-should-be-avoided’ dogma. These microbes were here first and our long-shared history with germs has cultivated an enduring marriage of mutual exploitation (we’ll explore this further in Chapter 3). The spectrum of disease faced by our immunity today has changed considerably from the infectious ones that challenged our health in the past. Germs may no longer be the main enemy we face but the war on our health certainly isn’t over. We have merely delayed and mostly transformed it.

Of all the major health threats to emerge, none has tested the foundations of public health so profoundly as the rise of chronic non-communicable diseases (NCDs), which include autoimmunity, allergy, metabolic dysfunction and some cancers. Immunity has a central role to play across the spectrum of these chronic conditions that have quickly replaced infectious diseases as the leading cause of premature death and disability worldwide. We are getting sick in the absence of infection – the Western world is experiencing a rising tide of lifestyle-related illnesses, with immune-triggering danger signals rife and immunity going awry. This trend is deadly, carries crippling economic costs and cannot be easily reversed under the conditions of our 21st-century lifestyle. While an infectious disease can spread fast and far and kill irrespective of age, complex modern NCDs are long-term conditions that develop silently over years – even decades in some cases – ending the lives of people still in their prime, figuratively if not actually killing them. But we should remember that for all the ways in which we seem to be sliding backward, we’re lurching forward too. Since the 1980s, in Western countries we have sharply cut down on deaths from infections and malnutrition. Thanks to medical advances, rising wealth and much else, infectious diseases now kill fewer people than non-communicable ones. Sounds like great news, right? Well, it would be. But we have simply replaced one with the other, to the detriment of our health.

The good news? Doctors, scientists and the general public are increasingly aware that this is happening. Getting a handle on your health earlier in life might just be the key to better outcomes for these long-term chronic conditions. But although these modern-day health challenges are linked heavily to lifestyle, we cannot ignore how life in the 21st century also makes it difficult for people to change what they do. We can ban smoking, clean the air, build cycle lanes, tell people to eat ‘5-a-day’, but it’s not always easy for people to alter their behaviour, and this is a big part of foiling non-communicable diseases. It’s also one reason why these diseases don’t always generate the same level of concern: they’re often regarded as the sufferer’s fault.

Autoimmunity: Friendly Fire and a Case of Mistaken Identity

You may have heard of autoimmune diseases – but what exactly are they? And who gets them?

Autoimmunity is like friendly fire – a condition in which the immune system is too active, and unchecked T and B cells grow overzealous, wreaking havoc on the body they’re supposed to protect. The body has a variety of fail-safes to ensure that the immune system doesn’t attack itself, the guardian Treg cells being a mainstay. But sometimes these safeguards don’t work or get weakened and we get an unwarranted inflammatory response towards ourselves.

The incidence of autoimmune disease is increasing worldwide by up to 7 per cent every year. Autoimmune disease is a large umbrella term, and there are over 80 diseases within it that are linked in some way. Each of these can be terrible, frustrating, debilitating and hard to diagnose. They are driven by the adaptive immune system with its long-lived memory, making them impossible to cure. Some of the most common ones include type 1 diabetes, rheumatoid arthritis and lupus.

The causes behind autoimmunity remain broad and murky, but what we know for sure is that there is rarely a single cause. In fact, some research suggests that all of us have a little autoimmune potential as a trade-off for having over 100,000 unique T and B cells, each with the potential to detect a different molecule. This gives us a broad-spectrum infection protection but at a potential cost, in that some of these white blood cells might mistakenly recognise molecules on our own cells. Most of the time our specialised immune regulatory systems act as a firewall that keeps any rogue cells with autoimmune potential in check. Any issues with immune regulation leave us wide open to any counterintuitive attack. A big clue that this is the case lies in the fact that people who develop one autoimmune disease are more likely to develop another, indicating a global immune dysregulation is at play throughout the body.

Genetic predisposition accounts for roughly 30 per cent of all autoimmune diseases and currently there are more than 20 associated genes, many of which are in the ‘compatibility’ genes. This goes a long way towards explaining why autoimmune diseases tend to run in families. One family member might have rheumatoid arthritis, one might have thyroid disease and one might have lupus. It might be the same gene causing each of these different autoimmune conditions. But then identical twins are identical in genes, but they are not identical in developing autoimmune disease. This tells us that genetics is just part of the picture.

The remaining 70 per cent of autoimmune diseases are the result of environmental triggers and other situations we encounter – for example, toxic chemicals, diet, infections, digestive issues, stress and other lifestyle factors. Exposure to the perfect storm of non-genetic factors may actually flip the switch to push the immune system in the direction of an autoimmune condition. These factors are referred to as the ‘mosaic of autoimmunity’. And to complicate things further, each of us is different. So the particular combination of factors that causes one person to develop an autoimmune condition may not do so in another. In other words, there’s no one recipe for autoimmunity.

In the following chapters I will explore some of the ways that we can reduce our risk for autoimmunity. None of these lifestyle modifications is a guarantee to prevent or stop autoimmune disease. But together they may help to lower your risk.

A big issue with treating autoimmunity is that the slow-burning symptoms take so long to become apparent, and by the time they do, your immunity has silently been damaging your tissue for years. If you are unfortunate enough to be diagnosed with an autoimmune disease, you’ll probably be told that it’s incurable but manageable. Many of the current therapies for treating autoimmune diseases work by suppressing the entire immune system and are likened to using ‘a cannon to swat a fly’. Consequently, while these therapies can successfully block an inflammatory response, they have the unwelcome side effect of leaving patients vulnerable to infection. Though there are many essential conventional therapies now available, I’ll share some complementary approaches to treatment throughout the book.

Allergy – The Scourge of Modern Life

Allergies are the close cousins of autoimmunity. They are the result of the immune system overreacting – not to us, but to benign things in our environment like pollen (in the case of hay fever) or to a specific food (such as peanuts). Allergies are immunity overshooting, creating inflammation in the body in response to something that doesn’t really pose much of a threat.

Our ancestors didn’t suffer from allergies, and anyone from Generation X will recognise that they were extremely rare even a few decades ago. In fact, before the 1990s, peanut allergies were so rare that there was barely any data on them. Incidence of allergies is now steeply climbing, showing no signs of abating. Like autoimmunity, this happens partly through genetics. Our collective population genes have changed little over this relatively short period of time, so can’t be to blame. It is likely that these modern-day epidemics are due to an environment and lifestyle that do not allow our immune systems to properly calibrate.

ALLERGY: A HISTORY OF A MODERN MALADY

In the 1880s British doctor Morell Mackenzie noted that hay fever, with its tell-tale summer sneezing through the pollen season, went hand in hand with culture. Hay fever was an aristocratic disease, implying that the higher we rise on the socioeconomic scale, the more this allergic reaction tends to develop. Medical science at the time deduced that hay fever was the result of the stresses of modern life, the cry of an immune system struggling with its environment, and Mackenzie went on to conclude that the typical patient was ‘a delicate, upper-class only child who subsequently developed into an emotionally and socially maladjusted adult’. In fact, although there are many influences involved, levels of urbanisation may be one of the strongest predictors for the prevalence of allergy in a population, both historically and in the future. This has been shown time and time again. Allergies are more likely to affect people who are more distanced from traditional upbringings. The history of allergy is perhaps a metaphor for our physical, emotional and cultural responses to our changing environment.

Cancer – A Nasty Trick on Our Immune Defences

Cancer is a wide range of diseases with a common characteristic: something goes wrong in the way the cells regulate growth, resulting in uncontrolled cell expansion. This happens deep in the cell at the molecular level, in the cell’s genetic material.

Cancer is somewhat a matter of odds – an unfortunate by-product of the way evolution works. Large and complicated animals like us humans are vulnerable to cancer precisely because we are large and complicated. Each time our cells replicate, there is a chance of a mutation. Some of these mutations are benign, some are useful, but others are dangerous. Though it may seem flawed, over generations we pass on tiny mutations in our genes via this system. These mutations select out certain physical attributes, or phenotypes, to our offspring helping them better fit their environment. This is natural selection. But natural selection is not natural perfection. The more replications, the higher the chance of cancer. This is why our risk for some cancers increases with age. As previously mentioned, our immunity is our main cancer-surveillance system. But cancer is ‘self’. It is part of us. So it can easily slip under the radar of our immunity cancer patrol. This is the cruel trick cancer plays on our immune defences. Some cancer cells present ‘Don’t-eat-me’ signals on their surfaces, instructing our immune cancer killers not to attack our own tissues.

While there is much evidence that exercise and healthy living can reduce the risk of certain cancers, reducing is not preventing. You cannot remove all risk. Lifestyle can have a huge influence on the risk of cancer overall. My dad – an active man, a farmer, non-smoker, rare drinker, never overweight and having never eaten a takeaway in his life – was diagnosed 12 years ago with colon cancer, one of the most preventable lifestyle-associated cancers. With a colostomy and chemo (and a lot of faith in Mother Nature) my father survived the illness and has enjoyed good health since then. But, as I write, my family and I are anxiously awaiting more information on my dad’s second cancer diagnosis.

Other than hereditary risk (mutations passed down in your family), and certain exposures and behaviours (like smoking), cancer is still pretty unpredictable. The older you get, the more likely it is that you will have it, and you might not even know it. And not all cancers have known lifestyle components. Even with the ‘perfect’ diet and lifestyle you are still at risk. But this doesn’t mean that making healthy choices is futile. In fact, around 1 in 4 cases of cancer could be prevented in the UK each year largely through lifestyle changes including stopping smoking, maintaining a healthy weight, eating a healthy diet, enjoying the sun safely, protecting against certain infections and cutting back on alcohol.10

When it comes to cancer, the good news is that taking care of your health will help you get through treatment and recover in better shape than your less health-conscious peers. From the earliest days of my dad’s cancer diagnosis, my mother instinctively stepped up her game to prioritise his wellbeing. Not a lifestyle overhaul, but paying attention to the little details: tweaks to his diet to ensure as much variety as possible and plenty of protein, prioritising sleep and reflexology to aid with the stress of such a diagnosis.

Metabolic and Lifestyle Disease

Metabolic syndrome – a cluster of metabolic aberrations that results in conditions combining diabetes, high blood pressure and obesity – is rampant. This clustering of risk factors doubles the risk of heart disease and increases that of type 2 diabetes five-fold. Research also links metabolic syndrome to an increased risk of several cancers. The diseases associated with metabolic syndrome can be chronic, debilitating and lethal. Even though each metabolic condition is different, these diseases share common features below the surface. Metabolic disorders are caused by a multitude of factors, but the immune system plays a role. Metabolic syndrome has strong inflammatory underpinnings often associated with deregulated immunity and reduced infection protection.

Something in our lifestyles triggers immunity danger signals that feed into metabolic deregulation. Many people with metabolic syndrome are overweight. Being over your healthy weight does put you at risk of metabolic derailment. In our modern environments it’s easier to over consume calories, sending immunity slowly awry, as we will explore in Chapter 7. Studies suggest that this link reflects the influence of chronic inflammation and elevated levels of hormones involved in metabolic processes, like insulin. But weight doesn’t tell the whole story, as we will see. The modern Western lifestyle hasn’t just changed our diet, but every facet of our way of life. Epidemiological studies confirm that most people affected by metabolic syndrome have multiple common lifestyle characteristics or behaviours. These include smoking, poor diet, obesity and physical inactivity – all identified as leading contributors to overall mortality, working together to increase the risk of chronic conditions and other negative health outcomes in adolescence, adulthood and old age.

Brain Immunity

Until recently, the brain was thought to be cordoned off from the peripheral immune system. It’s carefully tucked away behind a barrier to give it extra armour and prevent germs from getting in. But that extra barrier means that while most germy threats can’t invade the brain, the body’s immune system can’t easily get in either. So it is reliant on its resident immune police-force cells called microglia. These cells patrol the brain. They swallow up invading germs, chow down on dead neurons and also trim the ends of healthy ones. (Neurons are specialised nerve cells in the brain, whose ends connect to each other, passing messages back and forth. These conversations help us to learn movements, store memories and much more, but the cellular connections change over time. Some become stronger. Others weaken. Eventually, some old connections aren’t needed any more. So microglia step in as the neurons’ personal barbers, pruning off old, less useful connections at the ends of cells so that new ones can emerge.) This single type of immune microglia in the brain exists in multiple flavours, working as versatile all-rounders, not specialists. So when they go rogue (following serious infections, injury or psychological trauma) they play a key role in mental-health problems and neurodegenerative diseases that rob people of their minds, memories and the ability to go about their normal lives.

Studying the relationship between mental health and the immune system is a hot area in psychiatry and neuroscience; so much so that new terms have been coined to define the field: psychoneuroimmunology describes the bidirectional communication between the brain and the immune systems and immunopsychiatry is the biological dominance of the immune system in the brain–body relationship. Inflammation was once considered a passive bystander in the health of brain function. Advances in science are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis. As we will explore, research suggests that for tens of millions of people, certain neurological disorders might be caused by a malfunction of the immune system. In other words, it is not ‘all in the mind’.

A New and Dangerous Form of Inflammation

The discovery in the 1990s of a ‘new’ form of inflammation present in many, if not all chronic diseases goes some way to explaining the surge in our modern-day malaise. A subclass of inflammation, often termed chronic or ‘meta-inflammation’, is now used to define a form of low, smouldering inflammation. Unlike the short, sharp assault acute inflammation delivers, meta-inflammation is a long-term slow burn. It is not local to any specific area, but widespread, silently surging through your veins. New links between inappropriate inflammation and seemingly unrelated disease or disorders emerge in the medical arena on almost a weekly basis.

When inflammation shifts from short- to long-lived, there is a breakdown in immune tolerance and regulation, and major alterations in the normal functions of all our cells and tissues, increasing the risk for all non-communicable diseases. Chronic inflammation can also impair normal immune system functioning, leading to increased susceptibility to infection, tumours and poor responses to vaccines.

When someone is experiencing chronic inflammation, the causes are insidious, the ‘danger’ triggers are so subtle and the root issues can be difficult to pinpoint. Shaped through evolution, in an environment in which sedentary behaviour was minimal and calorie surplus was rare, immunity is not optimised to our present lifestyle. One of the first red flags for chronic inflammation was its link with obesity. But this slow burn can also be present without someone being overweight – it’s just the cumulative effect of our overall modern lifestyle, comprising a plethora of psychosocial and environmental factors. Modern living has disturbed the balance of the immune system, setting off the ‘danger’ alarm bells in the form of an inflamed molecular cascade. This reaction is slowly undermining our health, constituting a cause or complicating factor in many diseases. We may not even realise, until slowly the cracks start to show.