How Parasites Evade The Immune System
Chris - Parasites have to evade our immune system, don't they. So how have they worked out how to do that?
Mark - If you look at parasites, they are incredibly varied in the ways that they can evade the immune system. Don't forget that we've co-evolved with parasites over millennia. The eggs of helminth infections, which is a type of very successful worm infection, have been found in the faeces of animals living in the lower Pleistocene era.
Chris - So how long ago is that?
Mark - That's billions of years ago. So they've been around a very long time. They've adapted to our immune systems and we've learned to live with them to a large extent.
Chris - There's evidence that people who don't have parasites are less healthy than those who do in some respects.
Mark - Generally not. Parasites are defined as being pathogens that cause harm to their host. So generally people who are infected with a parasite will experience ill health as a result. However, the essence of this discussion is whether parasites are associated with allergy, and there is some evidence that that is the case.
Chris - Because haven't people compared, say, Ethiopia and the UK in terms of allergy, and if you look at parts of Africa you just don't find people with asthma and other allergies, as Carrock was saying.
Mark - Indeed and within Ethiopia, you will find that people living in urban areas have a higher incidence or prevalence of allergic diseases compared with people in rural areas. So there's certainly a strong ecological correlation.
Chris - So what do you think is going on?
Mark - There could be many things going on. People living in urban areas have more televisions and they live a different lifestyle. They're exposed to a number of different stimulants of the immune system to that of people living on farms. However in terms of parasites, it appears that as people move from a rural environment to an urban environment, they lose their parasites. People who live in the countryside certainly have higher levels of parasites.
Chris - Now what does that actually mean to the immune system though? If you've got a body full of these things, how do they create a kind of cloaking device so the immune system just doesn't see them? What are they doing?
Mark - Well that's a good analogy. Let's take a specific example: the schistosome worm or bilharzia as it's also known. This is a worm parasite that lives in the mesenteric vein, which is between the gut and the liver. They live there for several years and there are even examples of the worm living there for 20 or 30 years. It does this in a variety of ways. One of the ways in which it can evade the immune system for long periods of time is by coating itself in proteins that actually belong to the host. So it's a stealthy or invisible cloak. One of the other ways in which it can evade the immune system is by getting rid of its outer skin so it replaces any damage that's occurring on a regular basis. The other important way, which ties in nicely with allergy, is that it induces these T-regulatory cells in particular. We think it's up-regulating certain responses that dampen down the horrific allergic responses that are associated with it.
Chris - If you look at the levels of IgE that Carrock was talking about that drive the allergic response in someone like me with hayfever, in someone who's infested with the type of parasite you're talking about, schistosomiasis, aren't their IgE levels through the roof? So why don't they have allergies?
Mark - Indeed it's an interesting apparent paradox. I say apparent paradox because it's not a true one. In fact, what we think is happening is that the parasite is a potent up-regulator of these TH2 responses. So you might ask the question why don't people with parasites have allergies, but the key thing is that as the TH2 responses are also harmful to the parasites, the parasite combats that by producing lots of these T-regulatory cells.
Chris - You're also part of the Matangini Project. What's that all about?
Mark - That's a charitable venture that we've started within our research group. The main idea is that we wish to support the communities where we've been working. The group's been well established in East Africa for the last 25 years and we feel like every time we go there we want to give back something because of their cooperation. So what we're doing is trying to raise money for community projects. We talk to people in the communities about what's relevant and liaise with them. They identify projects that are important to them and then we try and raise funds for them here.
Chris - And what are you working on and what is the key thing to try and understand how you can borrow from biology and nick what these bugs have learnt how to do, which is to switch off allergy from the body's immune system?
Mark - That's one of the things that we're interested in. We work in Kenya and in Uganda and we're involved in trying to see what happens when we treat people for their parasitic infections. One of the things you might expect to happen is if you remove the regulation that the parasites are using to protect themselves then you may find a rise in allergic responses, histamine levels and so forth.
Chris - Does that happen?
Mark - That does happen but there are a few big buts! First of all, because the parasites have been very successful during their existence and kept your histamine levels very low, when you remove the parasite, the histamine takes a very long time to reach European control levels. This means that you don't actually die of anaphylactic shock when you suddenly take the parasite away.
Chris - So are people doing trials now to see if it's possible to simulate that effect?
Mark - Yes. If we understand the idea that if you have a parasitic infection then you're protected from certain types of allergy, then we can look at the work of someone like Professor David Pritchard up in Nottingham. He's actually involved himself in a clinical trial using hookworms to protect against asthma.
Kat - We had him on the show a couple of months ago, and it's not just about things such as asthma, but also diseases such as rheumatism and other autoimmune diseases.
Mark - That's right. Parasites have been used therapeutically in trials against Crohn's disease and ulceratice colitis.
Chris - How does that actually work? Are they producing factors locally or is this manipulating the body's entire immune system? Because for diseases like joint disease it's in very focussed tissue. So is it just having the worm physically in contact with the bowel wall that has some effect or is it something coming out of the worm into the blood stream?
Mark - The worm appears to be mediating local events at the bowel because it will be inducing the up-regulation of cytokines and that just calms everything down so you don't get this over-active immune response in the gut.