Immune Regulation

Information for General Public

Our immune system is made up of billions of immune cells called lymphocytes. These cells are continuously being produced in the bone marrow (B lymphocytes) and thymus (T lymphocytes) and circulate through our bodies until most commonly they die from neglect or aging. Each lymphocyte expresses a different receptor that enables it to detect a specific set of molecules termed antigens. When lymphocytes bind a foreign antigen, for example during an infection, they receive a signal to multiply and then destroy the infectious agent. Some of these cells persist after the infection and provide an "immunological memory", which is what happens when we are immunised.

The generation of lymphocyte receptors is done at random because otherwise the infectious agents would find a way to develop resistance, just as they do in response to antibiotics. As a consequence it is inevitable that sometimes lymphocytes will carry receptors for self-antigens - in other words, they will react with molecules in our own bodies. When these cells are generated they normally receive a signal to disarm, a process that is called immunological tolerance. The signals to disarm operate by causing the cells to commit suicide (deletion), become inactive (anergy), or turn into specialised regulatory cells, called suppressor cells. It is when immunological tolerance breaks down that we develop autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis

Our aim is to understand the development and regulation of lymphocytes and in particular the processes that lead to tolerance or autoreactivity. This knowledge is fundamental to improving the treatment of autoimmune diseases, the development of better vaccines and the outcome of transplants. We are also interested in new ways to monitor immune responses and the effects of current therapy.

Information for students

Self-reactivity is the defining feature of autoimmune diseases, which affect 3-5% of the population. These diseases arise from failures of mechanisms that stop our own immune cells reacting with self proteins. Analysis of quantitative and qualitative changes in the functional characteristics of immune cells and signaling molecules provides a rational and feasible approach to identify the causes of autoimmune diseases in individual patients.

This programme of translational research is applying our existing knowledge of immune function to predict and follow markers of the immune response in patients with autoimmunity and immunosuppression.  We are studying lymphocyte subsets in patients using flow-cytometry and developing assays of function in single cells, including phosphoflow and antigen-induced proliferation. One priority area is the study of follicular helper T cells (TFH) and the expression of Roquin-dependent proteins, notably ICOS, in a variety of autoimmune diseases, including rheumatoid arthritis, SLE and vascultiis. This is a direct extrapolation from our basic science models which have suggested a critical role for these cells in autoimmunity. Additional assays under development for the analysis of patient samples include anti-viral T cell MHC tetramers, ELISPOTs and methods to identify antigen-specific autoreactive B cells.

This work is funded as part of the Oxford Comprehensive Biomedical Research Centre (