How does an allergic reaction happen?

The effects that allergies can have on people can be life changing - but what exactly happens inside the body during an allergic reaction, and how has our understanding of allergies changed in the last few years? The University of Manchester's immunologist Sheena Cruickshank...

Sheena - What's happening is that you've already been sensitised to that allergen and you've made a particular type of antibody called IgE, immunoglobulin E. And that's stuck to these special white blood cells that are found in loads of our barrier sites like our skin, our lungs, or our gut. Depending on where those are, is where you're going to get the symptoms. Now, when the IgE sticks to it means your mast cells are armed, they're ready to go. And when you meet the allergen, that basically causes your mast cell to spew out its contents and it's like it's full of little weapons, these little packages of little chemical weapons, and they're what causes your symptoms. So one of the chemicals it makes is called histamine. And of course that's why we take antihistamines and it causes things like you to make mucus for you to sort of contract your muscles. So it's hard to breathe, for example, you to start getting these itchy eyes. It's all those sorts of symptoms and it's those naughty mast cells.

Chris - It seems strange that the body should do something so destructive in this way. Why do we have cells capable of unleashing this kind of maelstrom in our tissues at all? What's their intended role and why do they do this?

Sheena - Well, if you look back in history, particularly perhaps not always relevant to how we live now in a lot of countries, we have an ability to distinguish between lots and lots of different infections. And the arm of the immune response that is particularly associated with allergy, is the type that's really good at dealing with big parasitic worms and any kind of pathogen that sits outside our cells, what we call an extracellular pathogen. And worms were incredibly common all throughout the world, and they still are in many parts of the world. And in fact, you know, we've done research, in Quarry Bank Mill, which is just outside Manchester, and we found that that mill workers there clearly had evidence of worms back in the 18th century.

Chris - So these mast cells, which are in these, you mentioned them as barrier sites where our insides meet the outside world. Those are places where, historically, parasites like worms would've tried to get into us. And so these cells were a line of defense.

Sheena - Absolutely. They're there to be rapid defenders, but they also have a role in other types of infection. It's really important that we have cells that can act really, really quickly if we meet any kind of threat. And mast cells are brilliant at that.

Chris - Why does it go wrong and they become pro allergy then?

Sheena - Ah, that's the 10 billion question. We don't fully know the answer to that, but part of it is all in our genes. So some people are genetically more likely to develop an allergy, and we can see that when we look at family studies where we see, for example, if your parents have an allergy, you are more likely to develop an allergy as if you're a child of that parent and so on. And some of those genes that are associated with being more susceptible to allergy, they will affect the way that we respond. So they'll affect the way that we recognise an allergen, they'll affect the way that we then react to it. So often it's sort of centered around things around the response to IgE and how it sticks to cells or the response and barriers that would normally stop things getting in. But basically it's an immune response gone wrong. The other thing is that our world is changing and the things around us are changing. So climate change is changing how long and how intense the pollen seasons are. That has a real impact on us. And we know, and we and others have shown, that pollution has a really big impact and it can make the severity of your symptoms much, much worse. And also it means you have longer symptoms as well. So there's all sorts of factors that are coming into play.

Chris - I must admit to being surprised when I first read that, that people who live in cities, particularly ones with high traffic and therefore high pollution burden, often have worse allergy problems than people who live in the countryside.

Sheena - Absolutely. And we don't fully understand the reason for that. There's a lot of different hypotheses as to why that happens. But one idea is the way that our immune system gets trained and whether we have a really kind of nice diverse surroundings and microbes and different things that are in the air, our environmental microbiome, as well as the food that we, and the way that we develop our internal microbiome. So those microbes that live inside us and on us and around us seem to be really important in how our immune system develops. And it's been shown, for example, that babies who get a lot of antibiotics when they're very, very young and their immune system is developing, that changes the microbiome and that's been correlated then with them being more likely to develop an allergy. So there's something around that kind of relationship with the environment and our food and all sorts of things that is quite important.

Chris - This gets dubbed the hygiene hypothesis as well, doesn't it? The claim that our lives are so sterile in the modern era because of various cleansing agents that allegedly remove 99.9% of microbes and so on, that this leaves the immune system almost twiddling its thumbs. So it skews the way it develops and matures down a path that leads to allergy more often.

Sheena - I think that was the original idea. And this was coined by David Strachan, back in I think the eighties. And he noticed this observation that smaller family groups and people who lived in the city were more likely to develop an allergy, and he thought it was because they were getting less exposure to germs around them. But this idea of thinking about the types of infections that we get, for example, whether or not we get worm infections or the type of microbes that live inside us and on us has sort of overtaken that original idea. So now we think of the old friend's hypothesis and the idea that it's just that all that environment that's shaping the development of our immune system rather than how sterile we have been

Chris - When we try to manage allergy people usually reach for a box of antihistamines. How does that actually work and does it really work? Is there a better strategy?

Sheena - Well, there's lots of different strategies that you can use, but I think for most of us, antihistamines are very accessible and that's one of the main chemicals that those mast cells release, and it's one of the main effectors that cause the symptoms of allergy. So by blocking the action of the histamine, you should be able to block the system, the kind of the impacts that it's having. But you have to take those things regularly. You can't just take them and then leave it for a few days. It does sort of build up. But then there's other ideas about, well, could we just try and dampen down the inflammation? And that's things like taking steroids and inhalers. They're about dampening down more, sort of more generally that inflammatory response and relieving the symptoms and the effects that those chemicals are having. Or you know, there are more preventative treatments that are being investigated as well.

Chris - I had hay fever when I was little. I got enormous benefit through being desensitised, a sequence of injections that apparently made my body a lot more tolerant of the things that I was originally allergic to. Is there any merit in that?

Sheena - Yes, there is. There's been some fantastic studies, particularly in food allergies and I think it's, what's really happening is it's about redirecting the immune system so that you do not make IgE anymore. That you're either making a different type of antibody which won't stick to mast cells, or you're making a regulatory response and that stops you getting inflammation.