Published on October 29, 2020   33 min

Other Talks in the Series: The Immune System - Key Concepts and Questions

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I'm Herman Waldmann from the Dunn School of Pathology, University of Oxford, and I'm going to talk to you about tolerance to self.
The first way I can define self-tolerance is the physiological state where the immune system does not react destructively towards "self," and perhaps I would add, even when provoked.
Why is it important to understand tolerance mechanisms? Why am I giving this lecture? Well, it's important that we understand how the immune system breaks through the mechanism that stops it reacting to self. Because if know that, you know what you have to do to make vaccines work. You know what you have to do to generate the best immunity against cancer. It gives us understanding also of how tolerance may be broken when some people get autoimmune disease. What goes wrong in diabetes? What goes wrong in multiple sclerosis? How did it break? Because when we know how it broke, then we can offer, perhaps, more precise treatments. How it can cancer evade immunity? Now that's a big area that has flourished in the last few years, and I have written a chapter on which I refer you to because I'm not going to be able to cover it today. But it's quite clear that cancers can produce novel proteins, foreign proteins, and yet the immune system somehow doesn't realize that they're there. So how is cancer operating to behave as if tolerant or to make the immune system behave as if tolerant? If we want to cure autoimmunity, instead of giving immunosuppressive drugs, we want to understand what went wrong with tolerance in case we could reprogram the system again to get it right. When people overreact and produce hypersensitivity, allergic reactions, why are they doing that and how can we reduce that? If we can work out how to regulate that more effectively, then we will be doing well. Finally, it's a big goal in transplantation to hijack the tolerance mechanisms so we don't have to give so many nasty drugs that penalize the immune system when we don't need to.