5 threats to your immune system–and how to fight them | Prof. Daniel Davis MBE

0:00Welcome to Zoe Science and Nutrition, where world-leading scientists explain how their research can improve your health.

0:15Walk into any store and you'll see rows of supplements claiming to boost your immune system. We all want to avoid being sick during the winter months, so these products can seem tempting. But do any of them really work? And is trying to boost your immune system really a good idea?

0:34To help us understand, we're joined today by Daniel Davis, Professor of Immunology and Head of Life Sciences at Imperial College London. He's published 145 scientific papers and authored four best-selling science books. Daniel has researched immune health for 25 years and helped discover the immune synapse, which revolutionized our understanding of this system. Today, he'll help us bust some myths about the immune system and explain how immune health is linked with mental health. Most importantly, he'll tell you how to support your immune system. By the end of today's episode, you'll know what you need to do to reduce your risk of catching cold or flu this winter.

1:13And just as importantly, you'll know what won't help.

1:19Dan, thank you so much for joining me today. Thanks, Jonathan. It's wonderful to be here. I'm aware that our immune system helps to fight off like these microbes that are out there in the world trying to infect me and make me sick. And honestly, every time a scientist starts talking about the immune system to me, I end up feeling more confused at the end of the conversation than at the beginning. So I think it's brilliant that we have one of the world's leading experts on the immune system here to hopefully clear this up for me. And I imagine for many of our listeners, too. so can we just start at the beginning really which is like what is the immune system and why is it so challenging to study the immune system is very complicated i'm sure people are very aware of the importance of your immune system in fighting off all different kinds of infections it's also important in preventing us from succumbing to other kinds of illnesses cancer and all sorts of other problems that can arise in our health it's inherently complicated because it has to fight off all different kinds of possible infections, including infections that have never before existed in the universe.

2:22A new type of virus could arise at some point, and our immune system has to be able to fight that. So the immune system is there to fight off things that are potentially dangerous, but not attack any normal part of your healthy body. And to some extent, every single cell of you is part of your immune system because almost all the different types of cells that make up the human body actually have some ability to know when they are infected with a virus for example or when they are turning cancer so most cells of the body have already some inbuilt sensory mechanism to detect when they themselves have a problem and they could signify to other bona fide immune cells that they have a problem.

3:13So all of your body is part of the immune system. I mean, one thing I heard really clearly was that not only does it have to be incredibly good at attacking sort of these bad things outside, but it needs to be really smart at recognizing whether this is actually part of my body, so it mustn't be attacked. I'm interested that you mentioned that just in the summary. Is that a very important part of what it needs to do in order to be healthy? Absolutely. Because you will know that there are any number of products and ideas telling you how to boost your immune system. And on the face of it, that sounds quite a simple thing that we want to be doing.

3:52But having just told you the complexity of what the immune system has to do, a layer of depth in the idea of boosting the immune system is immediately impairment. What does that actually mean? If you just somehow boost the ability of your immune system to be very active and start fighting things, then you don't want to do that because it would inadvertently start attacking things that are part of the normal, healthy body. And that would then cause you problems in itself. So it's important that we understand the complexity and the nuance in what the immune system has to be able to achieve, because already we're at the point where some of the sound bites and clickbait you might come across for do this one thing to boost your immune system already now we could be questioning what does that actually mean i don't want to just boost my immune system in a very general way to make it more active i need it to be restrained in some situations because i don't want the immune system to react against my own body or things that are not particularly harmful to me like would happen if your immune system started reacting against food or something and gave you an allergic reaction.

4:57One of the things I thought of as you were describing this, like not reacting to things that are normal in the environment is seasonal allergies or hay fever. And I'm probably thinking about that because I get this now regularly, which I never did as a kid. Is that an example of like my immune system? You know, I mean, sometimes we belittle allergies because they're not spoken about in the same way that cancer is because allergies are not really a top 10 cause of death. But the number of people who get allergies you just mentioned you get allergy i get allergies hay fever as well and it's two billion people so allergies are incredibly important and by and large they are the outcome of our immune system reacting against something that is not particularly harmful like it could be pollen as an example but there are many different types of allergies of course so just even that knowledge in itself hopefully means that thinking about the complexity of the immune system means it's all about having the immune system react to things that are truly dangerous, but not overreact against things that are not really a problem for the body.

5:59There's another side to that as well, which is that when you do get a genuine infection, a virus infection, let's say, and your immune system has to deal with that. So that involves a heightened state of your immune system. The particular cells in your body that are good at fighting that virus have to multiply a number. You might experience a fever, depending on what type of infection it is. But then, again, you don't want your body in that heightened state of immune activity, because that would put it at risk of overreacting against something that's not harmful. So a lot of what we're talking about in good immune health is keeping the immune system balanced, rather than, you know, utterly boosted in some way.

6:39And I get the impression that maybe we don't come back to balance as much as perhaps were designed to? I mean, you talked about the allergies, 2 billion people with allergies. I just remember my grandparents sort of telling me that almost nobody had allergies when they were growing up. I don't know if that's true. Are we like coming back to normal in the same way that we are meant to? It's a very hard question to answer. I mean, the number of people diagnosed with allergies has been increasing. And some of that could be that we're better at recognizing allergies than we used to be. It could be true that we are more susceptible to certain kinds of illnesses we used to be.

7:17And again, another reason for that might be that we're living longer on average. As we age, our immune system changes. Some autoimmune diseases do tend to arise more as we age. So there are many factors in the increasing prevalence of an immune system problem. In terms of allergies, one of the things that you might be thinking about is the effect of our microbiome. And there's this general idea that perhaps being exposed to something like a less hygienic environment or to microbes when we're younger trains our immune system to be better at dealing with allergies. So that comes from wonderful and pioneering research by Gordon Strachan at St.

7:57George's Hospital in South London. We're not too far from where we're speaking right now. And he made the observation that large families, the younger siblings tend to develop less allergies or less hay fever. And he had the idea that perhaps in a larger family, especially a younger sibling was more exposed to infections when they were younger because the older, the other people in the family might get infections. So you have this idea that perhaps an exposure to germs when you're younger somehow protects you against allergies. And he called that the hygiene hypothesis, which probably many of their listeners will be somewhat familiar with.

8:33that does also correlate with studies of children growing up on farms one particularly careful study or a group of studies if you like has looked at different communities in the usa and one group essentially lives nearer to where animals live and and the environment where animals are and they are less likely to develop allergies than another farming community that tends to use mechanical farming tools and live further away from where the animals live. So that again fits with this idea of the hygiene hypothesis that more of an exposure to germs does somehow train your immune system to protect you against allergies when you're older.

9:11But as we've said right at the outset of this podcast, everything is very nuanced and complicated and there could be other explanations to those farming data. For example, unprocessed milk also is used in farms which may also have some protective benefit we understand very little about what that is from my perspective as a scientist i've kind of been trained to kind of hear something and then think of like 10 other explanations of why that might be true rather than the one that i've just been told and it's exactly the case in this that there's lots of possible explanations for how growing up on a farm may influence the onset of allergies and the bottom line is we don't know enough about the details of how that works to give us an actionable outcome.

9:54And it's particularly difficult because I couldn't take dust from an animal house on a farm and somehow expose children to that to see what happens because you would be exposing healthy children to something that we understand very little about and is even potentially dangerous and that just isn't ethically possible to do. So it's very hard to do the experiments to find out what is it. Is there some important ingredient to the environment of growing up in a farm that helps train our immune system. And right this very minute, we don't know enough detail to make this an actionable thing that leads to any advice.

10:33So we have to be very careful about explaining what the results are, what the experiment is. Another notification. Something else to add to the to-do list? Is it work? Is it life admin? Or maybe another email from your boss? Your heart rate might be quickening at the thought. After all, life is full of little moments that add to our mental load. If you're feeling wired, tired, irritable, or on edge, that's your hormones responding to everyday stresses. They're trying to tell you something, and your diet could be part of the solution. Your gut is a hormone factory, producing and responding to all the hormones that affect your hunger, mood, energy levels, and stress responses.

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11:55I'm listening to this and thinking that much of the world has sort of gone through an unintended experiment about this sort of hygiene hypothesis. And so many of us lived through COVID, there was sort of social distancing, we were definitely much more conscious, many of us about wash our hands, we weren't with other people. I know from speaking to doctors that there was like this really big fall of many other infectious diseases through this period. And then obviously, we've all gone back into life. So I imagine that you're going to tell me like over the next decade or something, there's this sort of fascinating, almost worldwide intervention to see whether or not this has had any impact on our immune systems.

12:32Yeah, so that's a very interesting point. And that's exactly true. The pandemic has opened up a lot of what our immune system is, does, how it changes. Obviously, everyone experienced different symptoms and outcomes from being infected with COVID-19. And that correlated very precisely with things happening in their immune system. So we did learn a lot about that. And the learning is continuing. You talked about cancer. And I guess when I was thinking about immune health, it's like it's all fighting off viruses and infections. How does cancer fit into this? Many decades ago, people did think that cancer wasn't really anything to do with the immune system because, I mean there are some rare occasions when cancer can be caused by a virus but most of the time cancer is just your own cells that are dividing in an out of control way and so it's your own body's cells gone wrong and so your immune system doesn't have anything as obvious to look at as you know the spike protein of the covid virus that is definitely alien to the body but we have dramatically changed our view of that the immune system can definitely see cancer developing in many ways, in fact.

13:39Two big ways. For a cell to turn cancerous, mutations arise that make the cell start to divide, multiply in an uncontrolled way. And then that leads to some changes in the protein molecules that that cell makes, and your immune system can directly detect those changes in protein molecules. That's one way. Another way is that when a cell becomes cancerous, very often that cell itself has an ability to know that it's dividing in an uncontrolled way. For example, its DNA might be damaged in some way, or if it was exposed to UV light, for example. And that cell itself can start to display molecules at its surface that tell the immune system, look, I'm damaged, kill me.

14:31So cancer can be seen by the immune system. It couldn't be more important because this does lead to all kinds of new medicines. One of the major new ways of us treating cancer in some patients is to use immune therapies that are called checkpoint inhibitors. We spoke earlier in the podcast of the importance of the immune system coming back down to its normal resting state after it's fought off a virus, for example. That's a very important process. The immune system has to be able to bring your body back down to its normal state once you've cleared out a virus. But if that process happens while your immune system is trying to fight off something like cancer, that would inevitably be bad.

15:13So in a long-term situation where the immune system is fighting off a cancer developing, you don't want the immune system to put the brakes on and come back down to its normal resting state. But that does happen. and so checkpoint inhibitors are a type of therapy where you block the brakes on the immune system from coming on and you keep up the immune cells being able to fight off a particular type of cancer and for some patients and it doesn't work for all patients doesn't work for all types of cancer but for some patients who have been told they have a short time to live now live for a much much longer time on account of these types of therapies checkpoint inhibitors so we go from basic science of what is the immune system you just asked me does it fight cancer yes it there's there was a revelation in in understanding the immune system can fight cancer and then not only is that important in its own right but that kind of insight very directly leads to developing new medicines that allow the immune system to fight off cancer so sort of right now and all the time one of the important jobs that my immune system is doing is effectively sort of scanning my body for any like new cancer and like hitting it before it becomes some sort of like bigger cancer that I might end up being aware of and a doctor being aware of?

16:25Absolutely true. So all the time your cells are becoming damaged through exposure, for example, to UV light, sunlight, or other things are going on in the body. And one of the jobs of your immune system is to kill off cells where cancer might be developing. And a lot of the time you would not be aware of that. In fact, it's quite hard to know how often in your body is a cell kind of on the way to turning cancerous and your immune system has killed it off again the experiments are actually really hard to do how would you know that if you're not aware of it so the immune system is one of its jobs is to stop cancer developing in the body and how often that happens how important is it's quite hard to know but it's definitely happening in your body and mine all the time i'm sure so there's probably something right now there's like a cell in my body that might be going wrong and my immune system is is zapping that.

17:13Absolutely killing it off. And this is the kind of research that my own lab does, actually. So we are watching these processes happen down a microscope to understand the details of what's happening. I invite you back probably to go deep into that. I actually want to ask another question, though, because you mentioned before, which I'm fascinated by, this idea that my immune system is completely different from my wife's immune system and your immune system. Why? One reason why your immune system is different to mine is simply because of the genes we have. You and I have the same set of genes, the sort of 22 ,000 genes that make up the human genome, but we all have slightly different versions of some of those genes.

17:54A small fraction of all the genome is a bit different between you and me. So that gives us our differences. And so people might think that the genes that are most different between people, the genes that vary the most between me, you and everyone listening to this podcast would be genes that control things that are just obviously different, like our hair color, our eye color, our skin color. But actually, the genes that vary the most between every person listening to this podcast are genes in our immune system. So right off the bat, at that level of how our genes vary, your immune system is pretty much the most unique thing about you.

18:32This couldn't be more important. So if you got infected with a virus and you said your wife got infected with the same virus and she recovered quicker than you, that might well be one reason for that would be that she might have a different version of immune system genes. I feel like she would argue it's just because of like my moral failings and like just complaining too much and not getting on with life. Jonathan, right, that flippant jokey comment couldn't be more important to me because one of the things that i personally take away from the fact that we all have different immune system genes is that if you get a virus and i get a virus and you recover in two days and i'm flat out ill for a week because we're bombarded with a lot of messaging about health exercise you know do this stuff i'll be thinking oh no, Jonathan's probably going to the gym every day and he's not stressed and look, his whole life is wonderful.

19:32And look at my life and I'm ill for a week. But that is not true. It could just be that by chance you've inherited genes that will make you better at detecting that type of virus. So we mustn't blame ourselves. There's another really important take home message from that, which is that this is a fundamental story about human diversity. There's no inherent hierarchy to our immune system genes. No one has a better or worse set of genes, really. Our diversity in immune system genes is what makes all of us stronger. And there are very clear examples of this. So if you have a particular immune system gene called HLA-B27, you are more likely to develop a particular type of autoimmune disease and closing spondylitis.

20:18It doesn't mean that if you're hanging out with that gene, you're likely to get that autoimmune disease, but it means that people with that autoimmune disease are more likely to have that gene. On the face of it then that means that that particular immune system gene would be bad to inherit. But actually if you're infected with HIV there's a big difference amongst people of how long it takes to develop AIDS and people with that particular immune system genetic inheritance are more likely to spend a longer, much longer time from infected with HIV to when they would develop AIDS if they weren't treated.

20:49so it means that that particular immune system gene correlates with them being better at fighting off the virus HIV so immune system gene but on the one hand seems to have a negative consequence it's more likely correlated with some autoimmune disease developing is good for you in another sense that it correlates with you helping fighting off HIV so this is really important because it means that the worst things that have ever happened to humanity have happened because of a misunderstanding of what our diversity is. It is fundamentally important to how we live and how we survive different kinds of diseases.

21:25I'd love to switch on to talk about some of these myths that we understand about the immune system. And you've already talked about the idea that boosting it is bad. I'd love to talk about vitamin C because I wasn't feeling very well last week and my daughter's babysitter immediately said, oh, you should go and take lots of vitamin C. And I was like, I'm pretty sure I've heard from people that maybe this doesn't really work anymore. What are the facts? So vitamin C is actually a really fascinating story. I mean, vitamin C is important for health, no question. But the thing that we're talking about here is about our immune health.

22:01I've been brought up thinking, if I have a cold, right, drink some orange juice and you'll be fine. And that somehow made sense to me, but it's really just a prejudice. It's really just something I've been brought up with. And now I'm trained to be more skeptical about these things and think about what is the actual evidence, what are the experiments? I started to look into that more. And actually, it turns out that the way we think about vitamin C has been hugely influenced by one individual, Linus Pauling, who won two Nobel Prizes. He wrote a scientific paper on the nature of chemical bonds and the journal it was published in the scientific magazine if you like that published it said normally we send this to be looked at by other scientists but in this case there's no one in the world that is good enough to judge this particular piece of work we'll publish it anyway it was that level of scientist later in life he campaigned against nuclear bombs and he won a second nobel prize this time for peace so he was someone that we are listening to and he was very easily seen on the TV and radio.

23:08In 1970, he published a book on vitamin C and the common cold and boom, new factories had to be built to keep up with demand. Everyone is listening to him. We need higher doses of vitamin C. His argument was that the level of vitamin C that we were told to have comes from a level that was known to stop you getting scurvy, which is something that happens if you're very deficient in vitamin C. And his argument was that, well, that's not the same as knowing how much is actually healthy for you to have, just that it avoids a particular illness. He cherry-picked the data that was out there and basically, through anecdotes, came to the conclusion that we need more vitamin C and it would help us fight off colds.

23:52Him and his wife, Ava Helen, they both took about 10 times the amount of vitamin C that's recommended and felt it gave them a lot more energy for tough colds. He actually also said that high doses of vitamin C will stop you getting cancer, all sorts of other things. Now, the truth is vitamin C will not stop you catching a cold. That is unequivocally proven in clinical trials and tests. The people who have a regular supplementation of a high dose of vitamin C, on average, get over a cold about 8 % quicker, which would mean that if you're ill for a few days you might get better a few hours earlier if you supplement with a high dose of vitamin c even that information alone is very difficult to act on because people that take a high dose of vitamin c are probably doing other things in their lives as well which might make them get over a cold a bit quicker so it's very hard to know but by and large vitamin c is not going to help you with a cold so for me the take-home message is not only that orange juice isn't going to help me with my cold.

24:56It's also that we need to be very, very careful about any one person's opinion. Well, I think you've just demolished taking vitamin C in order to stop getting a cold. I'd love to come on to one other myth. And we got this a lot, but it made me actually think of my grandmother who used to always say, now we're getting into the winter, wrap up warm because otherwise you're going to catch a cold. Is that true? Wrapping up warm won't stop you catching a cold, but it is true that there is a seasonal variation to the types of viruses that are multiplying well in a particular season, and it does make us more susceptible to the cold in a certain time of year.

25:38Help me to unpack that. So you're saying that I'm more likely to catch flu and a cold in the winter, but it's not because I am physically exposed to the cold? yes there's some limit to that because if you were so cold that your health was affected in a general way then you would maybe succumb to the symptoms of the cold more if you looked after yourself in a general way and kept warm your body would be in a stronger position to be able to deal with an infection dan i'd love to switch to links between immune health and mental health because we've talked a lot about protection against diseases and against cancer but i know in your book you also discussed that it's not just physical health that the immune system is somehow engaged with.

26:21Is that right? When your immune system is fighting off a virus infection and you might experience a fever, you know that a fever is affecting you mentally as well as physically. Obviously, your temperature is raised. I mean, I feel rubbish whenever I'm sick. I complain all the time. Everyone at Zoe knows that. Everyone at home is like, I'm like a terrible invalid. I'm incredibly frustrated because I want to be doing all this stuff, but I just feel tired and I feel like my brain is like somehow, like everything is like cotton wool. In hindsight, it feels obvious that our mental health is somehow connected to our immune health.

26:54Perhaps some of that has evolved deliberately. Like if you have an infection, then you feeling weaker, tired, staying in bed is good for you in terms of helping your healing process, but also it's good for humanity because you're not wandering around affecting everyone else. So some of that process is very likely to have evolved in a very deliberate way. Now, there are some very interesting experiments looking at whether more generally than that, our immune health is connected to our mental health. It's very hard to assess anybody's immune health in any way because it's so complicated. So Dan, there's not just like a simple blood test that just gives me a scale on my immune health in the way that I might get a sort of cholesterol check?

27:37I think the answer has to be no for the moment. But one of the ways we can get some sense of what's happening inside a person is to look at the particular types of molecules that immune cells use to communicate with each other. So during an immune response, as we've mentioned, there are lots of different kinds of immune cells in the body, and they have to communicate with each other. And one of the ways they do that is that an individual cell will produce a protein molecule that comes out and then goes and touches another immune cell. And those kinds of molecules are called cytokines. And there are over 100 different types of cytokines, and they do all kinds of things in the body.

28:19In fact, it's a bit unfortunate to me that cytokines aren't more famous. They deserve more public recognition. They're easily as important as antibodies, which people have probably heard of. I would predict over the next decade cytokines are something that everyone listening to the zoe podcast is going to have heard more about cytokines there are over 100 of them they're how immune cells communicate with each other now cytokine levels flux up and down in the body in your blood anyway during the day different ones are rising in the morning in the evening etc but you can measure cytokine levels to give some proxy of how much the immune system is in a state of activation in a person.