The immune system is the body's major defence against infection. However, an effective response against micro-organisms requires means to detect them. Thus a major issue in immunology is the study of how the body brings about this self- versus non-self discrimination or, as some would suggest, harmful versus non-harmful discrimination. This issue involves almost all the regulatory mechanisms within the immune system. An understanding of the principles underlying the regulation of the immune system is the major goal of research within immunology at Cambridge. Such principles can be harnessed to achieve improvements in the control of infectious diseases and in the therapy of autoimmune disorders and certain cancers. The Division of Immunology has major research programmes in autoimmune disease, in immune cell signalling and differentiation, antigen processing and presentation, the molecular genetics of the MHC and NK receptor gene clusters and therapeutic immunology. The Part II course in immunology reflects these research interests, as well as providing an up-to-date overview of the subject.
The course can be broadly divided into the following sections:
Molecules of the immune system: Structure and genetics of immunoglobulin, T cell receptor and MHC molecules. The biology of cytokines and their receptors. Lymphocyte activation and cell signalling.
Cells and cell interactions in the immune response: The origin and function of T cells, B cells, natural killer cells, antigen presenting cells, e.g. macrophages and dendritic cells and other haemopoietic cells. How these cells co-operate to mediate key immunological functions, such as antibody production and T cell activation. The cell biology of antigen presentation. Lymphoid architecture and lymphocyte recirculation.
Effector functions, immunity and transplantation: The molecules and cells involved in the recognition and killing of parasites, micro-organisms and virus infected cells. These include activation of the complement system, interaction of immune system (antibody molecules and T cell factors) with cells of the innate immune system, eg macrophages, neutrophils and eosinophils. The action of cytotoxic T cells and natural killer cells. How these effector functions can be harnessed by immunisation. Basic principles of transplantation biology and therapeutic approaches to control rejection.
Tolerance and autoimmune disease: The mechanism of tolerance induction; significance of central and peripheral tolerance. The key role of the thymus in T cell ontogony and self-/nonself-discrimination. How tolerance breaks down to produce autoimmune disease. The nature of these disease states. The immunobiology of materno-feotal interactions Therapeutic strategies to control autoimmune disease, including therapeutic antibodies.
The projects are usually based on the research interests of the teaching staff. These include: manipulation of antibody molecules for therapeutic use; mechanisms underlying autoimmune diseases such as diabetes; function of cell adhesion molecules and non-classical MHC molecules, using transgenic biology techniques to study these, and the mechanisms of lymphocyte activation and the control of the cell cycle. In addition to the projects within the Immunology Division of the Department of Pathology, some research projects are offered by other departments, e.g. The Clinical School Departments of Medicine and Surgery, The Veterinary School and the Cambridge Institute for Medical Research. These may include topics on lymphocyte signalling, viral and bacterial immunity, rheumatoid arthritis and transplantation biology.
Examples of Current/Previous Projects
- Investigating the factors affecting the detection of the binding between human IgG molecules and human FcγR.
- TAPBPR: A new player in MHC class I processing and presentation.
- T-cell subset differences in the expression and function of CD146.
- Regulation of MHC protein turnover in vivo or Antigen presentation pathways following transplantation.
- Analysing auto-reactive T cell responses during tolerance induction.
- Reverse genetics in the NOD mouse.
- The peptide-binding regions of certain chicken and mammalian class II A chains are nearly monomorphic and nearly identical: what is that telling us?
- The mechanism of Salmonella interference with MHC class II expression I: role of peptide loading and HLA-D.
- The mechanism of Salmonella interference with MHC class II expression II: involvement of E3 Ubiquitin ligases.
- Making TAPBPR specific monoclonal antibodies.
- Endothelial adhesion molecules on T cells in patients with Sjögren’s syndrome.
- Regulation of MHC protein turnover in vivo.
- Investigating the properties of the human IgG constant region pseudo gene.
- Examining the effects of Salmonella typhimurium on Type 1 diabetes.
- Antigen presentation pathways following transplantation.
- Vaccine design: antigen structures identified by broadly neutralising monoclonal antibodies to HIV envelope.
- The immunological synapse and cilia.
- Maternal killer cell immunoglobulin-like receptors (KIR) and fetal HLA-C in pre-eclampsia – a family study.