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Skip to 0 minutes and 15 seconds NICK JONES: So my name’s Nick Jones and I’m a senior lecturer in the Institute of Immunology and immunotherapy here at the University Birmingham. As you already learned, the immune system is composed of several different types of specialised cells, some of which include T and B cells, have receptors on their surfaces that enable them to directly recognise pathogens or infected cells. But every pathogen looks different. So the question is how can the immune system respond to any pathogen that is out there, including pathogens that we have yet to encounter, but not recognise our own bodies. Well, Evolution has come up with a really ingenious and phenomenally powerful solution. And central to it, are our armies of T and B cells.

Skip to 0 minutes and 58 seconds The receptors present on the surface of T cells and B cells called the T cell receptor B cell receptors respectively, are unusual. Because unlike most receptor, they could be made in potentially millions of different visions. These different versions are generated at random, and each individual T or B cell carries a single unique version. This system means that we have a vast pool of T and B cells, each of which has a unique form of the receptor on its surface. The size of these pools mean that for every pathogen infection that we are faced with, there is likely to be at least one T or B cell and possibly several that they’re recognising.

Skip to 1 minute and 39 seconds This system is really powerful because it provides a way in which we can mend a strong immune response against essentially any infecting bug. Even ones that we haven’t been exposed to before. But there is one big problem with it. Within the vast repertoire of different T and B cells, there will inevitably be ones with receptors that have directed to our own bodies. In other words, that are self-reactive. So, how do we get around this? Well, this is where the second ingenious step comes in. During the development, the T and B cells are deliberately exposed to our own proteins, and any T or B cell that recognises them instead of becoming activated, is programmed to die.

Skip to 2 minutes and 22 seconds For any self-reactive cells that escape destinational process and make it to maturity, there are a number of other factors that are in place to keep them in check. For example, some may never become activated because they never meet the protein that they recognise. For example, immune cells recognising proteins found exclusively in the brain, where immune cells are generally excluded. Others may recognise proteins present in sight are protected from immune-like attack, such as the eye which is good as dampening down any immune responses. Another key point is that for a protective immune response to develop, our immune cells need information.

Skip to 3 minutes and 2 seconds If our self-reactive T and B cells encounter our own proteins in the absence of inflammation, they prematurely die or become inactive, rather than making any response. Finally, any self-reactive T cells that escape these control mechanisms may still being kept in check by special regulatory T cells, which play an absolutely essential role in dampening down immune responses. So then collectively, the result of these processes is that we develop a repertoire of T and B cells that are largely tolerant of our own bodies, but have the potential to recognise any foreign invader that we encounter. So in the next task, you’ll find out what happens if this system of immune tolerance breaks down.

Immune tolerence

Your task: Watch this video in which Dr Nick Jones, a Senior Lecturer in Immunology at the University of Birmingham, describes how our immune system is controlled to enable powerful responses against foreign invaders without damage to our own bodies.

Reflect on any new information or ideas and share your thoughts with other learners in the comments area.   If you would like to find out more about how immune tolerance works, here are links to an NIH webpage and IMGT web document (see page 26) on the topic.

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This video is from the free online course:

Cancer Immunotherapy: a Step Change in Cancer Treatment

University of Birmingham