Immune responses to viruses

Published on April 29, 2020   45 min
My name's Paul Klenerman. I work in the Nuffield Department of Medicine at the University of Oxford, and I'm going to talk about the immune responses to viruses.
The aims of this talk are to overview the roles of adaptive immunity in responses to virus infection and learn about some of the methods used to investigate the world of specifically T cells in immunity to infection using neuron systems and what we've learned from those experimental systems. Then we're going to look at what happens in studies of human infection. And hopefully through all of this we'll understand the key mechanisms that regulate the immune responses to infection and particularly chronic infections, of which the most important two are escape and exhaustion.
In this figure, we're looking at adaptive immune responses to a virus infection, and the point of this slide is to show that the different types of immunity are linked together. So you can see there's a CD8+ T cell, a CD4+ T cell, and a B cell. They're all recognising different parts of the virus. They're using similar tools, but they're doing it in parallel ways. So between them they can get a good grip on what's going on in terms of a virus infection. So let's start with the CD8+ T cell that has a T cell receptor, which is recombined to create an enormous amount of diversity. So the T cell receptors can recognise MHC molecules, which are illustrated binding a peptide which is bound to the group of the MHC class I molecule that can be recognised by the T cell. Now how does that peptide get there? The virus infects a cell and a protein from the virus is generated. And like all cellular proteins, these are then degraded by the proteosome and small peptides are pushed through the TAP transporter and loaded in the endoplasmic reticulum onto the class I molecule and pushed to the surface of the cell as a complex with beta-2 microglobulin. So the CD8+ T cell in this sense is recognising proteins from the virus that are present within the cell. In the middle of the slide,