What happens when our immune system doesn’t work as it should?

I consider myself lucky: I don’t wait for the onset of summer with trepidation, knowing that it will bring days of itchy eyes and sneezing. For others, though, the blossoming of our natural world through spring and summer is less a time for marvelling at the wonders of nature, and more a time for an annual battle with hay fever. But why do some people have to suffer such afflictions while others don’t? What’s going on?

As I’ve mentioned in earlier posts, our immune system protects us from attack from potentially dangerous alien invaders in our surroundings. But sometimes even the best systems can go awry, as hay fever demonstrates so clearly.

The symptoms of hay fever – the itchy eyes and runny noses – are a consequence of the reaction of our bodies to pollen in the air. On the one hand, pollen is an alien invader (after all, it’s not a natural part of our body), so you might think it’s a valid target for attack by our immune system. However, it’s a harmless intruder, whose presence won’t actually cause any damage if left alone. So, in fact, there is no real benefit to be had from our bodies mounting an attack against it. Indeed, this is why, for many people, no attack is mounted. (It’s a bit like having both a neighbour’s cat and a poisonous snake wandering into your garden: the cat might not belong there, but at least it won’t do much harm. You’d struggle to feel the same about the snake. It’s a question of knowing which battles are worth fighting.) For others, though, the lack of danger posed by the intruding pollen isn’t recognised by their immune system, and the familiar response I’ve noted above is triggered.

Hay fever is an example of an allergy – the inappropriate response by our body to something that isn’t actually a threat. This inappropriate response takes the form of our immune system over-producing a particular type of antibody – but it is the knock-on effect of this antibody over-production that we really notice. As I mentioned in a previous post, antibodies can summon other parts of our immune system into action. When we suffer an allergic reaction, the overabundant antibodies sound a call-to-arms that triggers inflammation – localised swelling as the white blood cells of our immune system rush in to mount an attack on the perceived intruder. 

Sometimes this over-sensitive response is little more than an annoyance, as in the case of hay fever (though I should note that it’s a significant annoyance for hay fever sufferers); other times, an over-sensitive response can be life-threatening, as in the case of asthma, where the network of tiny tubes that form our lungs swell up, making breathing very difficult. 

It’s not just invaders from outside that can trigger an inappropriate response by our immune system, however. Sometimes, our immune system can turn inwards and start to attack components of our own body, wrongly considering them to be a threat. Such a response is called an autoimmune response. For example, rheumatoid arthritis – the painful swelling and degeneration of our joints – is caused by the white blood cells of our immune system attacking the cells in our joints, as if they were dangerous intruder cells. 

Similarly, a certain type of diabetes, in which an individual’s body fails to control the level of sugar in their blood, is also associated with the misbehaviour of our immune system; in this instance, the immune system attacks a certain type of cell found in the pancreas, the part of the body that manufactures insulin. Insulin is a chemical ‘messenger’, which travels round the body, controlling how much sugar is taken up from our bloodstream. When the pancreas is damaged by attack from our immune system, its production of insulin is impeded and, with it, the vital control of our blood sugar levels.

So what causes our immune system to malfunction in these ways? While we don’t yet understand enough to have all the answers, allergies, in particular, seem to stem from the way the immune system is ‘trained’. It may seem odd to say that the immune system needs to be ‘trained’. After all, our heart doesn’t need to ‘learn’ to pump blood; our skin and nails aren’t educated in the art of growth. But our immune system does need to learn – and one way is for it to be exposed to germs and the like during childhood. Increasingly, however, this isn’t happening. 

As a child, growing up in a relatively rural part of the UK, I spent much of my time outdoors, playing in the garden, or tramping over local fields, and getting exposed to plenty of old-fashioned dirt in the process. Now, however, children spend much of their time in dirt-free zones, slumped in front of the TV, or huddled round games consoles. And this clean living comes at a price: we are seeing a significant increase in the incidence of asthma in countries of the Western world, where children are growing up in increasingly germ-free surroundings. It seems possible that, by being exposed to too sterile an environment, our immune system may not be encountering a sufficient number of potential threats to learn how properly to differentiate between harmful and harmless, and risks becoming overly-sensitive to things that are, in fact, harmless. (This is a possibility set out in the so-called ‘hygiene hypothesis’ – but is something that remains a hypothesis, rather than an irrefutable fact.)

There are also lots of questions around how our immune system fails to ignore ‘self’ – that is, why our immune system wrongly turns against the cells and tissues of our own body. Early in life, our immune system is ‘trained’ to ignore self: those white blood cells (the B cells and T cells that I mentioned in my last post) that recognise self are eliminated. But, for reasons that are still being explored, this process of education clearly isn’t quite enough. Sometimes it seems that the information stored in a person’s genes makes them susceptible to autoimmune diseases; in other cases, environmental factors such as certain bacterial and viral infections seem to be a contributory factor.

Whatever the answers prove to be, it remains the case that we would live in constant peril if we had no immune system at all, as by those with severe combined immunodeficiency (SCID). These individuals have such severe defects associated with their T cells and B cells that they can only survive, without treatment, if kept in a completely germ-free environment, as so heart-wrenchingly demonstrated by the case of David Vetter, whose childhood spent living in a plastic, sterile bubble led him being known to the world as the ‘bubble boy’. The rest of us have a lot to thank our immune systems for – even if they don’t behave quite as intended 100% of the time.

How are bacteria and viruses different?

In my last post I discussed how our bodies protect us from the threat of attack from our surroundings. Two of these threats take the form of bacteria and viruses. But is there any major difference between these two invaders? In short, yes – and we’ll explore what this difference is during the rest of this post.

Let’s start by thinking about bacteria, and how they differ from the cells from which our bodies are made. By contrast with the sprawling metropolis of cells that form our body, a bacterium (we talk of a single bacterium, but many bacteria) is just a single cell. And unlike the cells of our body, which rely on each other for survival, a bacterium is a self-contained living entity. Inside that single cell is all the machinery needed for the bacterium to survive, along with that all-important element of life: a genome; the genome contains all the information needed to instruct the formation of a new bacterium, allowing the continuation of life. A bacterium feeds, grows, reproduces and dies, mirroring our own existence, but at the level of a single cell. However, bacterial cells have distinct differences from other cells, the cells of our bodies included. For example, the building materials used to construct a bacterial cell wall are quite different from the materials that encapsulate each of our cells. These differences are important, as we’ll see a little later.

So what of a virus? In short, a virus is nothing more than a neatly-packaged instruction manual. A bacterium contains its own instruction manual – its genome – but also all the molecular machinery needed to read and make use of that instruction manual: it can use its genome to maintain its own existence (and does so very effectively). By contrast, a virus simply contains a set of instructions – its own genome – but none of the machinery to bring those instructions to life. So how does it survive? Well, in the absence of its own set of molecular machinery, it steals a set from elsewhere – namely, from a living organism like us. When a virus infects us, it hijacks the molecular machinery found in each of our cells; this machinery stops reading the information stored in our own genome, and starts to read the viral genome instead.

When a viral genome is ‘read’ by a cell, two things happen: the cell makes more copies of the viral genome, and more packaging to wrap it in. The virus is basically hijacking a living cell and using the cell as a photocopier to generate multiple copies of itself. So why is this such a problem? In some cases, it isn’t: some viruses infect us without there being any adverse effects – and, indeed, without us ever being aware that the infection has happened. Others, however, are much less forgiving. In some instances, once the hijacked cell has made copies of the viral genome and new packaging to wrap it in, the cell bursts, releasing its newly-built viral cargo, but also killing the cell in the process.

By contrast with viruses, bacteria seem almost to be tame, and certainly don’t hijack our cells to drive forward their existence in the same ruthless way that some viruses do. Indeed, some bacteria are entirely harmless to humans: we have 1.5 kilos of bacteria in our gut alone, which carry out a range of useful functions. Other bacteria are less accommodating, however, and release toxins, substances that our bodies find poisonous. It is these toxins that cause our bodies to react in ways we associate with ‘being ill’ – for example, the bouts of diarrhoea and vomiting that we could all live without.

So how do we defend ourselves against these particularly harmful invaders? The key issue for our own wellbeing is that we want to eliminate the alien intruders without damaging our own cells. A bottle of bleach might well do serious damage to some invading bacteria, but it would do just as much damage to our own cells too. Not an ideal solution. The problem is compounded when it comes to viruses: the ideal solution would be to switch off their means of reproducing – but as that means of reproducing is us – our own cells – we’re left having to find other solutions. The key is to find a way of discriminating between ‘them’ and ‘us’. So what options are there?

I mentioned earlier how bacteria are encased by cell walls that are made from different building materials than those that are used to build our own cells. This is just the kind of difference that can be exploited to our benefit. Some antibiotics – naturally-occurring or man-made chemicals that destroy bacteria – can selectively target and destroy bacterial cell walls (having much the same effect as a sledgehammer on a brick wall) while leaving our own cells intact.

Viruses are somewhat trickier beasts to overcome; as I mention above, if we were to target the machinery they use to reproduce, we’d be targeting our own cells. Instead, we need to find ways of stopping the virus getting into the cell in the first place. Typically, the first step in a virus attacking a cell is its attachment to the outside of that cell. If we can prevent the virus from clinging on to the cell surface, we can stop it from subsequently getting inside to wreak its usual havoc. And this is exactly what some vaccines do: they stimulate the production of antibodies, which essentially act as cellular bodyguards, getting in the way of the virus and its intended target.

We don’t have antibiotics and vaccines to protect us against infection by all bacteria and viruses, but only those that have the potential to do us particular harm, and which could overwhelm our immune system before it had chance to respond. Other bacteria and viruses – the ones that cause us merely some annoyance and discomfort (such as the viruses that cause the common cold) – are removed through the protective action of our immune system, as explained in my previous post.

The eagle-eyed amongst you will have noted an important point above: antibiotics and vaccines attack bacteria and viruses in different ways. This is why there’s no point taking antibiotics to treat a viral infection: the antibiotic just won’t work; they’re designed to do a completely different job. You wouldn’t eat a peppermint and expect it to relieve a headache; equally, you shouldn’t take an antibiotic and expect it to cure a viral infection. So, your GP diagnoses you with a viral infection, don’t think they’re neglecting you if they don’t immediately write you a prescription for an antibiotic; to do so will be of no benefit to you at all. In fact, taking antibiotics unnecessarily can do more harm than good, as I’ll explain in a future post. 

How does our immune system work?

Each day of our lives is a battle for survival against an army of invaders so vast in size that it outnumbers the human population hugely. Yet, despite its vastness, this army is an invisible threat, each individual so small that it cannot be seen with the naked eye. These are the microbes – among them the bacteria and viruses – that surround us every day, and could in one way or another kill us were it not for our immune system, an ingenious defence mechanism that protects us from these invisible foes.

Our immune system is a multi-layered operation, much like the fortifications mounted to protect medieval castles. Our first line of defence – the equivalent of a castle moat – is our skin, a physical barrier that separates the hordes of microbes in our environment from the cells of our bodies that lie beneath. However, our skin does not keep us sealed off completely from our surroundings; indeed, some gaps in our defences are essential for our survival. And two gaps are very obvious: our nose and mouth. 

Every minute of every day we inhale air deep into our lungs. But along with the oxygen molecules we so desperately need come other less desirable particles, including viruses and fungal spores. Fortunately, we have another barrier in place to prevent these less desirable particles getting where we don’t want them. The lining of our lungs is covered by a layer of mucus, which traps many of these particles. Under this layer of mucus lie millions of tiny finger-like protrusions that bend from side-to-side, generating a Mexican wave-like movement that wafts this detritus-laden mucus up and out of our lungs, to be expelled (to put it as delicately as I can) every time we cough up phlegm or blow our noses.

Our requirement for food also leaves us exposed to the threat of invasion, this time via our digestive system. Once again, though, we are primed to defend ourselves. The inside of our stomach isn’t the most hospitable of places: it is highly acidic – perfect for aiding the digestion of food, but not a great place for many bacteria to set up home.

Despite the best efforts of these first lines of defence, however, the most determined invaders succeed in their mission and infect us. But this isn’t the end of the fight as far as our bodies are concerned: when our outer defences are breached a whole army of cells are in place to protect us. These cells are our white blood cells. 

The white blood cells operate as two separate battalions. One battalion is on the constant look-out for any general signs of trouble. In this respect, it acts a bit like a bouncer in a nightclub, who is primed to respond quickly and decisively to any one of a number of general ‘alarm’ signals - be it signs of a scuffle on the dance floor, or signs of inebriation from a late-night reveller. Whenever the alarm is raised inside the body, our first battalion is called to arms, and responds equally quickly and decisively, often simply by ‘eating’ whatever intruder first raised the alarm. 

This approach lacks what one might call any refinement: it is a fairly indiscriminate one-size-fits-all strategy. By contrast, the second battalion acts in a much more specific way, more akin to a group of snipers, each waiting for their particular target. This second battalion has two regiments – the B cells and T cells: B cells police the areas of the body outside of individual cells, including the blood; by contrast, T cells monitor the inside of cells. So how is the specificity of this second battalion achieved?

To answer this question, let’s focus on the B cell. B cells produce special Y-shaped molecules called antibodies. An antibody is like one half of a two-piece jigsaw: its specific shape allows it to recognise – and bind to – something with a complementary shape (just like neighbouring pieces of  a jigsaw fit together because their shapes are complementary). In the case of antibodies, however, the other piece of the jigsaw is a foreign object, such as a bacterium. The binding of an antibody to a foreign particle is one of the general alarm signals that call our first battalion to arms. So, the two battalions of white blood cell work together, with the second ‘sniper’ battalion often helping to focus the activity of the first on a particular invader.

Of central importance to the operation of our immune system is the fact that each B cell produces a uniquely-shaped antibody. Consequently, each antibody will recognize something different. This is important when we consider that our bodies face many different sources of danger, including many thousands of different microbes: we need lots of different antibodies to recognise them all. 

When we get infected by a specific type of bacteria, however, our bodies won’t be facing just one or two cells, but a whole army. We need lots of antibody to tag all of these invaders for destruction – but there’s no way we can always keep in circulation enough B cells to produce all the antibodies we need to destroy all the different microbes we might ever encounter. Instead, our immune system has a clever way of ensuring that large numbers of a particular antibody are only produced when actually needed. So how does this happen?

B cells circulate throughout our bodies in a continual surveillance mission, waiting until they encounter a foreign particle that can bind to their particular antibody (which, at this point in time, is protruding from the B cell like a probe). As soon as recognition happens, the B cell rapidly proliferates, stimulating the production of many copies of its particular antibody, which is now available in sufficient quantities to ‘tag’ many members of the invading army. This rapid proliferation is the reason why it feels like our ‘glands are up’ when we’re fighting infection: these ‘glands’ are our lymph nodes, specific areas around our bodies where B cells accumulate while they undergo proliferation; this accumulation occurs to such an extent that the lymph nodes actually swell.

The ingenuity of our immune system doesn’t end with the way it can detect many different foreign particles: it ‘remembers’ if it has encountered a particular invader before, and responds all the more rapidly (and effectively) if it encounters the same invader again. This memory is exploited by various vaccines, which ‘trick’ the immune system into thinking it is being attacked by a fully-fledged threat (when, in fact, it isn’t). When the body is subsequently exposed to the real threat, however, our immune system can mount a full-scale attack on the invader much more quickly than it could have done if encountering the invader for the first time. Indeed, the priming of our immune system by vaccines is essential to defend us against particularly nasty invaders, which could kill us if the immune system hadn’t already been primed.

This post leaves a number of questions unanswered. For example, is there a difference between bacteria and viruses, and what does this mean for how we defend ourselves against them? We’ll explore these questions in my next post.