This blog has been created partly as a companion to Chemistry for the Biosciences, the textbook that I co-author with Tony Bradshaw, and to act as an archive of posts I write for other sites (particularly the OUPblog). Like the book itself, it explores how life on the scale of atoms and molecules has an impact on biology - at the scale of cells, tissues, and organisms - and seeks to demystify a range of biological and chemical concepts.

The blog's name takes as its inspiration the cover of the first edition of Chemistry for the Biosciences, which depicts a gecko seemingly clinging to its surface. To find out what links geckos to chemistry, read this.

Sunday, 9 October 2011

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.