Institute of Immunity and Transplantation


NK T-cell lymphoma


How the body remembers infectious threats

5 November 2019

How does the body remember infectious threats it has met before and protect the person from getting the same disease, for example childhood infections such as chicken pox or after vaccination?

Killer T cells

This is the puzzle being worked on by Professor Ben Seddon and his team. “My team does the more fundamental research – the kind of work needed before we can get to the point of being able to translate understanding into treatment,” explained Prof Seddon.

“We want to understand how immune memory works – how your body remembers whether or not it can fight off a particular infection or disease. This is important because it’s how vaccines work and is now also being exploited by some immunotherapy treatments against cancer.”

It was recognised as far back as 430 BC, during the plague of Athens, that people who had survived the disease could nurse people with the disease without getting ill again. Although this and later  observations were exploited by Edward Jenner and Louis Pasteur in the development of vaccination, the underlying mechanisms still have to be uncovered if we are to be able to develop all the vaccinations and immunological treatments we need.

“We still don’t fully understand how immune memory functions and how the immune system manages to remember that chicken pox encounter it had as a child or a cold that’s going around, “ said Prof Seddon. “We don’t have vaccines for the common cold, HIV and malaria, for example. So there’s still a lot of work to be done.”

One of his key tools is mathematics. “We try to understand how memory works as an integrated system, using computer models and simulations. We want to be able to predict how the immune system can remember things and understand the rules that control that process.

Immune system memory

“It’s similar to the way that meteorologists use computers to predict the weather - they have an understanding of how weather systems work and the rules of high and low pressure, so they can make predictions. That’s the sort of approach that we use. “We want to understand how immunological memories work using computer simulations and models, then we can make predictions about what’s needed to make a good memory and how long it might last. We can then apply that knowledge to making more, and more effective vaccines.”

Another potential benefit of this work is the ability to understand the ageing process better and help people live healthier lives for longer. “People’s immune systems start to slow down and there’s a risk that it is not working properly as you get older. This is a real problem.”

Finding room for cells

T-cells are at the core of his research. “What we’re trying to understand at the moment is the sort of population dynamics within the T-cell memory. Memory is ‘encoded’ in our immune systems by different populations of memory T-cells for each infection. You can imagine that when you get a cold you’re going to be making new memory cells and one of the big questions is how are you going to manage all these different mixed populations?

“You have memories from your vaccinations, from your encounters with colds and illnesses and you’ve got to store all these in limited space. How does the immune system decide
which ones to keep and which ones to let go?”

He said that mathematics was the “perfect” language for expressing and understanding these cell behaviours. “Mathematics can distil the highly complicated behaviours that govern these systems into very simple rules. It probably wouldn’t cross your mind when studying maths at school that one day you might use a simple equation to express a highly
complex aspect of the human immune system, but it is a very practical application of maths.”

He’s looking forward to the move to the Pears Building. “I’m hoping that with a greater number of researchers coalescing within the Pears Building, there will be more opportunities to interact and find new applications for our mathematical approaches and analyses. It will be a great chance for us to explore and translate our ideas into a more clinical setting.”