Professor Carrock Sewell, University of Lincoln
Part of the show Allergies, the Immune System and Parasites
Chris - Allergies are obviously a manifestation of how the immune system works, but what actually is the immune system?
Carrock - The immune system isn't one thing, and we use the term 'immune system' as a short cut to avoid saying immune systems: there are loads of them. You can find them in everything from plants to insects to all sorts of animals. Through evolution we've adapted to cope with the onslaught of pathogens. All the germs, viruses and everything that tries to invade and kill us, we've evolved to deal with in various ways. Our immune systems are the tools that the body uses to do that with.
Chris - What are the bits and pieces that do it? What does it have in its arsenal?
Carrock - Well if you draw the immune system out, it makes the underground map look basic. So there's an awful lot to it. There are two key things that really help picture it in your mind. The first is that the immune system needs cells and there are a variety of cells in the immune system. Many of their functions are to go round, find a pathogen, and ingest it and kill it in some way, and there are a variety of ways in which it can do that. The clever part of the immune system is the eyes of the immune system. We often say that the immune system 'sees' a pathogen, but in fact it hasn't got any eyes, and even if it did, it's dark in there. So the immune system needs detectors, and the commonest type of detector, whihch everyone's heard of but doesn't really know what it is are antibodies. In our blood stream we have literally trillions and trillions of antibodies against almost anything conceivable.
Chris - But what actually are they? When you say and antibody, most people think of something that's alive in some way. I remember being at school when someone had written on the blackboard: 'Enzymes are not alive. They cannot be killed. They're bits of protein.'
Carrock - Well antibodies are other bits of protein as well. They're made by one of the cells in the body: the B-cell. They stick to pathogens very specifically, so an anti-polio antibody will only stick to polio and an anti-salmonella antibody will only stick to salmonella. But all antibodies come in one of nine flavours or isotypes. They, is you like, are the payload of the missile that is the antibody. So just as a bomb can be high explosive or armour piercing or whatever the captain has chosen that day, antibodies come in these nine different flavours and the effects of those are very very different.
Kat - So what are the antibodies responsible for allergies and things like that then?
Carrock - The antibody which causes allergy is called Ig, which is short for immunoglobulin. IgE: that's the nasty one but also probably an essential one and that has an unique property. IgE can recognise pathogens, but its payload is to stick it to a mast cell. The mast cell is stuffed full of histamine.
Chris - But why have that? Most people are only too aware of how nasty histamine is when it gets out of that cell. So why do we have it and what is its role?
Carrock - It's very poisonous to parasites.
Chris - Why? How does it work?
Carrock - I wish I knew!
Chris - So you have these cells that are like miniature hand grenades ready to be detonated and they have an IgE sitting on their surface. So what goes on to discharge that histamine? How does that work?
Carrock - The mast cell will be covered in IgE molecules against all different targets. It isn't that one mast cell is against this thing and one mast cell against that thing. Each of the mast cells in your body, and they live under the skin and in the blood vessels, each of those mast cells is coated in different IgEs. If a piece of pathogen or a piece of other protein comes past that mast cell and sticks to several IgE molecules at once, that sends a signal to the mast cell to burst and discharge. All the granules containing mainly histamine but also lots of other noxious molecules.
Kat - So that's what gives us the response:; the swelling and the hives and weepy eyes.
Carrock - Yes and that's probably quite a useful response. If you think about the types of things that are happening, many of them flush clear the area where the allergen, which causes an allergic response, has come into the body.
Chris - But the key question must be, everyone's got these IgEs, so why is it when I walk into a field of corn at this time of the year, get streaming eyes and feel a bit of a cough coming, but Kat might be fine?
Carrock - It's not just you, it's about 20% of the population that accidentally seems to make IgE flavour antibodies against harmless things like pollen rather that the IgG antibodies which the body mainly uses for fighting off bacteria.
Chris - So if someone is allergic, do they just have more of these IgEs or are they directed against things they shouldn't be? Do they pick up stuff they shouldn't?
Carrock - All the antibodies in your body are ultra-specific for a particular target. So you will have some IgE in your body against a;; sorts of things, but if you have enough of it against a certain type of pollen and you encounter a cloud of that pollen, it will send off the mast cells in your eyes and your nose and where you've breathed in those nasties.
Chris - So we've got to the stage where we understand how mast cells and the IgE is activated by something that provokes the symptoms. Do we know what's going on to provoke that in the first place? Do we understand anything about why some people do develop this mess up of the immune system and others don't?
Carrock - Well we understand parts of it and the picture's beginning to come together, but it's a rapidly developing field. One of the key things is how does your immune system decide to make IgE the allergic antibody versus IgG the other type of antibody. A lot of factors seem to be involved in this but one of the concepts which came about a few years ago is the TH1/TH2 hypothesis. What this means is the cells which control the type of antibody which is produced do so by making communication chemicals called cytokines, and they come in a number of families, one of which is called TH1 and the other is called TH2. The TH2 type of cytokines drive the immune system to making IgE instead. So it's often thought that the reason why people start to develop allergies is because their immune system has become more TH2 than TH1.
Kat - We hear a lot in the papers that maybe growing up in a very sterile environment has something to do with allergies and allergies are apparently on the increase in the UK. Is this actually true and is there any scientific evidence for this?
Carrock - There are a whole load of papers about this and this isn't actually the subject of my personal research, but when I've read large overviews of the field, it seems that there's this idea running through them that clean living somehow predisposes you to allergies. It is true that allergies are on the increase but actually when we look at people's homes, there are just as many germs there as there used to be. The only things that seem to make a difference in the predisposition to allergies in terms of the environment are the birth order: are you a first child, a second child or a third child?
Chris - Who's worse off in the birth order?
Carrock - Me, the responsible older one I'm afraid. My brother got the bike and a skateboard and I got the allergies.