Diversity in the Immune System

In case you are interested in my public seminar on "Diversity in the Immune System" for the Cambridge Festival today, I've uploaded the talk. Only shame is that it misses the hour of interesting and insightful questions from the audience afterwards!

I was also interviewed about this talk:

What fascinates you most about the immune system?

 

That is not a fair question! There are so many aspects of the immune system that are simply amazing. The immune system is our most powerful sensory system – capable of detecting even single molecules and responding to them. It is also incredibly powerful – given the right signals, millions of immune cells can be rapidly recruited from the blood into a tissue, where they can coordinate an attack powerful enough to liquify it. Yet this incredibly sensitive and enormously strong immune system almost never gets it wrong. It lies dormant until we get an infection, then usually responds with the minimal force needed to eradicate that infection. As immunologists we study the allergies, autoimmune disorders and inflammatory conditions that happen when the immune system slightly misjudges, but really it is amazing that our immune system messes up as rarely as it does!

Why are some people susceptible to certain immune diseases and others aren’t? 

Diversity lies at the heart of immunity. The best defence against pathogens is diversity in responses from person to person. You can think of the immune system having a dozen different default settings, which influence how we will respond to different pathogens. Each of these settings have trade-offs, they make us a little more susceptible to some immune diseases and a lot more resistant to others. It keeps pathogens on their toes, makes it harder for them to adapt to human immune systems, precisely because there is no single default immune response. From an evolutionary perspective the cost-benefit of all of these settings was probably fairly equivalent, but of course times have changed. Now days most people probably don’t appreciate the advantage that their increased susceptibility to pollen allergy may give in fighting off parasitic worm infections that they rarely get exposed to! 

 What causes this diversity in the immune system?

Good question! The single biggest effect is our environment. The air we breathe, the food we eat, the chemicals we are exposed to, the bacteria that live inside us. These environmental exposures are probably responsible for half of all of the variation in immune responses from one person to another – it is even more important than genetics. One of the ways we can see this is by looking at the immune systems of couples that live together. After couples having been living together for a few years their immune systems seems to converge in their settings, becoming much more similar to each other. This is almost certainly due to sharing all of those environmental factors. Did you know that you transfer as many as 80 million bacteria in a single kiss? So even the bacteria that live in our gut become more similar when we live together.

How about sex and gender? 

Sex and gender are perhaps less important than you might think. Together they are responsible for maybe 5% of the variation you see in the immune system from person to person. Similar to the level of difference you see in a smoker versus a non-smoker. The most interesting aspect about this effect is that we really don’t know how much of the effect is sex and how much is gender. Biological sex certainly can modify our immune system, but gender is greatly under-estimated. A simple example of hidden gender effects is bladder cancer. 3 out of 4 bladder cancer patients are men, which is often described as a sex bias. However the underlying cause of most of these bladder cancers are exposures to chemicals such as aniline dyes, which were previously used in factories. So the high risk of bladder cancer in men is not due to biological differences between men and women, but rather due to the gendered segregation of jobs. The immune system is highly responsive to environmental exposures, and is certainly modified by gendered exposures (smoking, workplace pollutants, personal chemical exposures, etc). So how much of the “sex effect” is actually due to gender? The answer will vary a lot, because gender roles and exposures are constantly changing.

Is it possible to reprogramme someone’s immune system? 

For sure. Quit smoking, take up exercise, change your diet – all of these will reprogramme your immune system. The problem is just that we have very limited data on how these link back to what we really care about – our susceptibility to immune diseases. Ignore any claims about “immune boosting” on herbal supplements or “health” food products; the claims have no scientific basis, and the immune system does not work so simply. It is fair to say that certain foods and gut bacteria will likely push the immune system in one direction or another, and that these changes may be beneficial for different immune diseases. At some point in the (hopefully close) future, we may be able to advise simple diet changes to nudge someone back to health. Right now, though, anyone making claims like this is probably selling snake oil!

What are you working on at the moment?   

The one really reliable way to reprogramme your immune system is through vaccination! A vaccine gives your immune system a sneak peak to a future pathogen, letting it train up before the infection hits. Proven protection from that one infection, leaving the rest of the immune system dormant. There is incredible science behind vaccines; they are probably the single most consequential discovery in the history of medicine. But there is certainly room for improvement – some vaccines are great, others are merely good, and some populations (such as older people) don’t get all of the protection that we want them to have. So our work looking forward is to understand the diversity of immune responses to vaccines. We want to see if we can take the lessons from the people who respond to vaccines really well and use that information to improve the quality of vaccines for everyone else.