Costimulation – Lymphocyte Activation

In order to activate lymphocytes, stimulation through the antigen receptor alone is not sufficient. You need what is referred to as co-stimulation. So here we have a T-cell, that’s a naïve T-cell, it hasn’t encountered antigen before. Its T-cell receptor is recognizing peptide MHC on the surface of an antigen presenting cell, like a dendritic cell. So this APC (antigen presenting cell) is showing peptide together with MHC to the T-cell receptor on the naïve T-cell. But actually nothing’s happening, because that’s the only signal that the T-cell is getting. And the result, if there is stimulation only through the antigen receptor, will be that there is actually functional inactivation of the T-cell; a process that is referred to as anergy. So there’s no response and we have a form of immunological tolerance. And this process of inactivating T-cells is very useful in preventing unwanted reactivity against self antigens. However, in the context of infection, dendritic cells become activated by the Pathogen-Associated Molecular Patterns present on microbes. And part of that activation of the dendritic cell, causes them to increase the expression of co-stimulatory molecules like the B7 molecules and also to release co-stimulatory cytokines such as interleukin-12. So in the context of infection, dendritic cells up-regulate the co-stimulatory molecules and cytokines that are required for T-cell activation. This will cause T-cells to themselves produce cytokines such as interleukin-2, and this will feed back onto the interleukin-2 receptor which is also expressed on these T-cells. And you’ll get extensive proliferation following activation of these T-cells, the development of effector T-cells, T-cell survival, proliferation and differentiation. The CD80 and CD86 B7 molecules are not the only molecules that are involved in co-stimulation. So here we have an example of a dendritic cell that is expressing the molecule CD40 on its cell...