In honour of the annual hoards of bleary-eyed hayfever sufferers, we are joined in the studio by Professor Carrock Sewell from the University of Lincoln, who describes how the immune system works, what causes allergic reactions and how we might be able to cure them, and Dr Mark Booth from Cambridge University discusses parasites, how they suppress and evade the immune system and how the Matangini Project attempts to provide parasite-free water in Africa. Sticking with the African continent, Derek Thorne travels to Tanzania to learn how to make ugali in this week's Kitchen Science.
In this episode
A Pill To Prevent Ovarian Cancer?
Ovarian cancer is often known as the "silent killer" as the disease is very difficult to detect until it has spread throughout the body, and more than 4,600 women die from it every year in the UK. In fact, Cancer Research UK are carrying out a large screening trial involving 200,000 women, to test whether a simple blood test or ultrasound scan can pick up ovarian cancer. But this week saw the publication of some interesting news. Researchers at the University of Athens in Greece have found that the humble drug paracetamol may help to prevent ovarian cancer, pointing towards new ways to prevent the disease. The team carried out what is know as a meta-analysis - pooling all the results from eight studies to include around 750,000 women. They found that for women who took paracetamol on a regular basis (for example, around a tablet every day), their risk of ovarian cancer dropped by a third compared to women who didn't take the drug regularly.However, long-term use of paracetamol can also have side effects, such as kidney and liver damage, and it may even increase the risk of other cancers, so it's not a good idea to rush out and start taking them if you're worried. But this research may pave the way for a large scale controlled clinical trial to test paracetamol's effectiveness. We also don't know how paracetamol might actually work to prevent ovarian cancer. It is likely that it works in a similar way to drugs such as aspirin, which can cut the risk of bowel cancer, by interfering with atype of enzyme called COX.
Haemophilia Treatment Researchers Cut To The Chase
Researchers at the Medical College of Wisconsin, Milwaukee, have developed a new approach to treating the bleeding disorder haemophilia, which also promises to get around one of the most common problems associated with the disease. Haemophilia occurs when a patient inherits a defective copy of a gene coding for Factor VIII, a lynchpin in the blood's coagulation pathway. The gene is bourne on the X chromosome, which explains why men, who only have one X chromosome, are more commonly affected than women. Haemophilia can be controlled by regular replacement injections of Factor VIII, but in up to 30% of patients the body begins to produce antibodies, called inhibitors, against the therapeutic Factor VIII, preventing it from working. Under these circumstances doctors are forced to resort to extremely costly drugs which can push the price of treating a single patient beyond US$1 million. To get around the problem Robert Montgomery and his colleagues have produced the cellular equivalent of a Trojan horse. Using engineered haemophiliac mice, the researchers added a healthy copy of the Factor VIII gene to the stem cells in the mouse bone marrow which make platelets - tiny pieces of cells which help to plug holes in blood vessels. The Factor VIII remained hidden inside the platelet, away from the immune system, until an injury occurred. At this point, platelets at the site of the injury then discharged their cargo of Factor VIII where it helped to orchestrate blood clotting. To simulate a patient with antibodies against Factor VIII the researchers then injected the mice with 5,000-10,000 times as much antibody as would be seen in a patient - and the approach still worked. This suggests that if a patient's bone marrow stem cells are collected, a healthy copy of the Factor VIII gene added using a virus, and then the platelet-forming cells are returned to the patient, it might be possible to effect a cure.
Making The Maths-music Connection
Why is it that a Mozart aria sounds tuneful and pleasant, while the works of modernists like Schoenberg and Webern are dissonant and unsettling? The key lies in the arrangement of the chords that make up the harmonies of the pieces, and now Dmitri Tymoczko at Princeton University in the US has developed a mathematical model to help understand musical structure. He has been building computer models that represent chords as points in geomteric space, so it is possible to analyse the relationships between the chords. He found that chords that from pleasing harmonies tend to gather together in geometric space, whereas chords that sound dissonant are found in different regions. This research can help us to understand why certain compositions are easy or difficult to listen to, and may help composers to understand more about harmonies as they write new pieces.
German researchers at the Max Planck Institute for Colloids and Interfaces in Potsdam, Germany, have designed a new coating capable of repairing minor scratches and preventing metal corrosion. Writing in the journal Advanced Materials, Helmut Mohwald and his colleagues have produced the mechanical equivalent of a slow-release medical preparation which is active only where needed. The team take tiny silica balls measuring 100 nanometres across and coat them with two polymers, polyethylene imine and polystyrene sulfonate, and a corrosion-killing agent called benzotriazole. The balls are then mixed into a zirconium oxide gel which causes the imine to become positively charged and the sulfonate to become negatively charged. This glues the two layers together, immobilising the benzotriazole between them. After it is applied to a surface, if the surface is scratched the silica balls fragement around the damaged area, discharging the benzotriazole which then blocks any subsequent corrosion. To test the new gel the researchers applied it to pieces of aluminium which were then scratched, both in the open air and in salty water. No corrosion occurred even with scratches up to 0.1 mm wide, which in a traditional setting are sufficient to trigger serious corrosion problems, particularly in the aerospace industry. The researchers are now working to modify the system to also protect iron and steel, perhaps even as an alternative to chrome-plating.
How to make Ugali
This week Kitchen Science travels all the way to Tanzania to find out how to make ugali, the staple food of Tanzania and other parts of East Africa. Derek speaks to Felicity Thompson, who has lived inTanzania for the past few years, about what ugali tastes like and joins Chelu George in her cafe in Iringa to find out how to make it. The great part is that you can make it at home too! Why don't you have a go at making ugali and tell us what you think.
To make ugali, you will need:
200g of maize flour or cornflour 1 litre of water boiling in a pan A bowl full of cold water Wooden spoon
How to do the experiment:
1 - Put dry maize flour into the bowl of cold water. Stir the mixture with a wooden spoon until it is well mixed in. If you don't mix it well then you'll get lumps!
2 - Pour the mixture into the pan of boiling water.
3 - Stir the mixture until the water returns to the boil. At this point the ugali starts to thicken, just like when you make gravy. Each granule of maize flour contains starch molecules. These molecules are long and thin and are tightly packed together in the dry granules. When the maize flour is heated in the boiling water, the granules swell and burst, allowing the neatly packed starch molecules to stretch out to their full length. Like strings of sticky spaghetti, the long starch molecules very quickly tangle with each other. By sticking together, the starch molecules cannot move past each other very easily, and it is this that makes the mixture thicken. This is exactly the process that occurs when you use gravy granules, except with ugali, you heat the mixture for much longer.
4 - Once the ugali has reached the consistency of porridge or oatmeal, add two more big spoonfuls of maize flour and stir it until the ugali is really thick. It is ready when it looks a bit like mashed potato, although the consistency will be much thicker. If you've been working hard at stirring, then there should be no lumps!
5 - Now it's ready to eat! The ugali can be very hot in the middle, so be careful not to burn your fingers.
How to eat ugali
Once you have a lump of ugali on your plate, use your right hand (everyone in Tanzania eats with their right hand) to break off a piece, roll it up and make it into the shape of a boat. You can eat the ugali as it is, but it's not very nutritious or tasty on its own. In Tanzania, people use the boat-shaped piece of ugali to scoop up a sauce, which could be anything from beans to something with coconut.
Why not have a go at making ugali and trying it with a delicious sauce? What does it taste like and do you think that ugali could catch on where you live?
- Science Update - Commitment Sprays and Children's Saliva.
Science Update - Commitment Sprays and Children's Saliva.
with Chelsea Wald and Bob Hirshon from AAAS, the science society
Kat - now it's time to head Stateside for this week's Science Update, where Bob Hirshon and Chelsea Wald look at a nasal spray that could put and end to marital strife and how your child's drool could reveal its stress levels.
Bob - This week for the Naked Scientists we'll be exploring your emotions and how your body chemistry regulates and responds to them, but first, Chelsea has some new findings on the so-called love hormone and how it could help even when your not feeling especially amorous.
Chelsea - In your brain oxytocin plays a vital role during sex and emotional bonding, and according to Emory University behavioural scientist Beate Ditzen, it could even help during domestic spats. At the University of Zurich in Switzerland she and her colleagues monitored a stress hormone in couples discussing unresolved conflicts. Couples that snorted an oxytocin nasal spray beforehand produced significantly less of the stress hormone. They also talked more openly about their feelings.
Beate - I interpret that as very positive that oxytocin made them overcome their avoidance of this self-disclosure during conflict.
Chelsea - She says the ultimate goal isn't to medicate marriages but to understand how natural fluctuations in oxytocin can affect a relationship.
Bob - Thanks Chelsea. Well one thing that can stress a relationship is incessant screaming, crying, demanding: no we're not talking about your spouse, but your baby. And tough as it is for you to listen, it's even tougher being an infant. Could that crying mean that your child is suffering from debilitating stress? Well now you can find out with a simple drool test. It measures levels of alpha amylase, a digestive enzyme found in saliva. Increases in the enzyme have been linked to stress in adults, and now a team led by Doug Granger, drictor of the behavioural endocrinology lab at Penn State University found that abbaies also produced more of the enzyme in stressful situations. In older children, higher alpha amylase levels were linked to social problems, academic difficulties and even physical illness.
Doug - We are hoping that measures like this will allow us to determine who is more at resilient and who is more at risk of some of those negative consequences of stress.
Bob - And the ease of a saliva test could lead to new insights and earlier interventions for droolers of all ages.
Chelsea - Thanks Bob. Next week we'll learn about eggs that can run away from predators. Until then, I'm Chelsea Wald.
Bob - And I'm Bob Hirshon, for AAAS the science society. Back to you Naked Scientists.
- Allergies And The Immune System
Allergies And The Immune System
with Professor Carrock Sewell, University of Lincoln
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.
- How Parasites Evade The Immune System
How Parasites Evade The Immune System
with Dr Mark Booth, Schistosomiasis Group, Cambridge University
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.
- What causes chronic rhinitis?
What causes chronic rhinitis?
Rhinitis is inflammation of your nose and hayfever is one of the types of rhinitis. So hayfever is a bit of a stupid name but it's one that has stuck, even though there's no hay and there's no fever involved. Inflammation of the nose can happen for lots of different reasons, but if you are allergic to a certain form of a pollen, then you may have allergic rhinitis. This means that when you inhale the substance you're allergic to, it triggers all those running, itching and sneezing symptoms in your nose. Nose sprays can play an extremely important role but the first thing to do is find out exactly which type of rhinitis you have. For that purpose you may need to see an immunologist or an allergist who specialises in allergies of the nose. They will undertake a series of allergy tests to find out what's causing the problem and how to avoid them the best. The next treatment is to reduce the symptoms in the nose and there are lots of drugs for doing that. There are all sorts of nasal sprays, although typically steroid nasal sprays which are much safer than steroid tablets and don't have the same side effects. Antihistamines are also a very common treatment, but there are other drugs too.
- Why do my allergy symptoms improve when I go to sleep?
Why do my allergy symptoms improve when I go to sleep?
It really depends on what kind of allergen is causing the symptoms, but it sounds like it's a type of pollen. Of course, when he's out and about during the day, he's going to be meeting that pollen, but when he's in bed, he's likely not to. The exception for this is whether he or his partner has long hair. I often find people with pollen allergies have terrible problems at night because one of them has very long hair. What we know about long hair is that it is a complete static pollen magnet. So if you wash your hair before you go to bed rather than when you get up in the morning, you can spend an allergy-free night without having a cloud of pollen around you.
- Is it common to develop new allergies as we age?
Is it common to develop new allergies as we age?
Children certainly do get allergy and allergy to nuts and some of the allergies go away with time. Unfortunately nut allergy tends not to. 85% of children with nut allergy will have it for life, but it's not impossible to develop an allergy later in life, and I often get patients who say 'why me and why now? I'm nearly thirty!' and I'm afraid it just happens. It certainly isn't an exclusion, so if you start to develop serious symptoms of an allergy in later life, get it sorted out because it can be an allergy.
- Why did my hayfever abruptly disappear?
Why did my hayfever abruptly disappear?
Presumably his immune system just got the hang of dealing with that pollen. Instead of making IgE antibodies against it, it presumably changed to making IgG. The other type of development in the immune system is when another type of cell comes along called the T-regulatory cell. That is allergen-specific but gives off cytokines, the communication chemicals that damp down the immune system. So whereas there used to be an allergic reaction, it may be that his T-regulatory cells have now got the hang of controlling that and that's great news for him.
- Why is sleep beneficial when we are ill?
Why is sleep beneficial when we are ill?
We have different patterns of hormones that go up and down during the 24-hour day and some of the healing hormones seem to be involved in the sleep phase of the day rather than the daylight phase of the day. But we're mending all the time, breaking down bits of the body and rebuilding it as we need it.
- Why am I allergic to the allium family of vegetables?
Why am I allergic to the allium family of vegetables?
It's not a particularly common allergy and I wonder whether she's had formal testing against that. All those plants are quite irritating in their own right. If I peel an onion my eyes and nose start to water, which is a bit like what you get with an allergy, but it isn't really an allergy that is there. She may or may not have had this proven by a proper laboratory test or a skin test.
- Does nose-picking and eating the products benefit our good bacteria?
Does nose-picking and eating the products benefit our good bacteria?
I think we train our immune systems quite politely without having to do that!
- The common reaction to allergy is a rash. Why is this and what good does it do?
The common reaction to allergy is a rash. Why is this and what good does it do?
A common to reaction to an allergy is more to have you nose run or to wheeze, but the same sort of process can happen in your skin. That histamine is making the blood vessels leak out their fluid rather than the red cells in them and that makes the skin swell up and go red. The mast cells that do this histamine release are also found in your skin. They're just under the skin. I think it's very important to realise that quite a lot of people get hive or urticaria most days of the year. In fact, they have chronic urticaria. This is not an allergy but many GPs will look at them and say it must be an allergy because they've got a rash. It never is in that situation and it's worthwhile seeing an immunologist or a doctor and getting that sorted out.