Published on October 29, 2020   61 min

Other Talks in the Series: The Immune System - key concepts and questions

Hello, my name is Iain McInnes, I'm the Muirhead Professor of Medicine and the versus arthritis Professor of Rheumatology in the University of Glasgow in Scotland. I'm going to tell you today about the principles of cytokine biology. I'm going to think out loud with you about the critical role that cytokines play in this extraordinary agile and dynamic immune response. I'm then going to tell you a little bit about their basic biology, how they're regulated, and finally give you some examples of how they can bring complex immune phenotypic regulation to bear.
The lecture I'm about to give you is going to fall into two parts. They're mutually dependent, but if you feel you would prefer take them as individual sub-segments, there's going to be no problem with that. In the first part of the lecture, I'm going to tell you about the principles of cytokine biology. I'm going to tell you what they are, I'm going to tell you how they function in the immune system. Then with that basis, I'm going to tell you just a little bit about a few select cytokine moieties and their potential role in the pathogenesis of diseases that are common in clinical practice. More importantly, how those cytokines and their biology have been used to derive new therapeutics that are transforming the lives of many people who have the so-called IMID group of disorders, the immune-mediated inflammatory disease group.
Let us turn first of all to the reason for having an immune response at all. It's interesting when you look back through evolution, that even very primitive organisms, even if you thinking about viruses, have devoted some of their invaluable genetic sequence and energy to the function of defense. Even viruses actually generated genes that were involved in the defense of the virus and the cell in which a virus might exist. Those genes actually have come through evolution into higher organisms, all the way through into sharks, into reptiles, into mammals, and even into the highest evolved mammal that is yet known, that is the Scottish football supporter. This is an extraordinary mammal that is immune to all manner of disappointments and terrible trials and tribulations on the sporting field, and even Scottish football supporters have an effective immune response. But if you just cast your eye through this figure, you will see that there has been a progressive acquisition of increasing modalities of immune defense. Initially, the immune response comprised mainly proteins, peptides, the complement system, for example. Then came the idea that cells could contribute. Finally, that cells could take on some specific functions which working as a corporate whole, could lead to an effective immune defense. A remarkable immune defense that in higher mammals allows not only the immediate response to a challenge, to an injury or to an infection, but also memory of that challenge so that when subsequently the human being or higher mammals sees that organism, it is able to mount an immediate and effective defense. That is the fundamental division of the immune response into innate and adaptive immunity that you'll be learning about in other lectures in this series. A good way to think about that is, of the innate immune system being immediate, highly effective, but amnesic. It does the same thing all over again the next time it's exposed to that same challenge. That's actually really quite inefficient. Mounting an immune response takes a lot of metabolic energy, it takes a lot of cellular material that takes a lot of building blocks to make new cells to respond. The acquisition of memory in higher mammals was the ability to remember what the challenge originally was, the context of that challenge in any given tissue and that rapid onset of a much more efficient adaptive response. What I'm going to tell you about is that, within this complex network, it is the cytokines that have a critical role in coordinating the immune response.