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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

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.

Research Projects

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

  • Dynamics of uterine natural killer cells during pregnancy.
  • Interactions between HPV oncoproteins and the breast cancer associated proteins BRCA1 and 2.
  • The role of human caspase 5 in the activation of the inflammasome.
  • A novel reporter Insulin mouse for in vivo imaging.
  • Identification of GPR35 dimerisation partners.
  • Computational analysis of Human Leukocyte Antigen immunogenicity in kidney transplantation.
  • Synthesis of Chicken MHC Class II-Peptide Oligomers of B21 Haplotype for Analysis of T-cell mediated Immune Responses to Marek´s Disease Virus.
  • Investigating the ligand for the only putative chicken lectin like NK cell receptor BNK.
  • The functional role of tertiary lymphoid organs in chronic allograft rejection.
  • The molecular basis of a novel mechanism of antigen presentation to T cells.
  • The role of Rasal1 in T cell signaling.
  • Identification and isolation of fetal macrophages from the placenta.
  • Expression of components of the avian peptide loading complex (PLC) in insect cells.
  • Analysis of Recombination in Natural Killer Cell Receptor Genes.
  • Identification and characterization of mouse trophoblast progenitor cells.
  • The interactions of wildtype and mutant human IgG with cynomolgus monkey Fc receptors.
  • Variability of the NK cell receptor that is detrimental for reproductive success: KIR2DL1.
  • Impact of chemotherapy drugs on the crosstalk between AML and NK cells.
  • The inflammatory response to DNA in the sera of patients with pre-eclampsia.
  • Is there mono-allelic expression of HLA-C in placental cells?
  • The role of XBP-1 in pro-inflammatory immune responses.
  • In vitro differentiation of Embryonic Stem (ES) to Dendritic Cells.
  • New approaches in MHC antigen presentation.
  • Development of a cellular-based reporter system to assess LILRA1 and –B2 ligand interactions.
  • Role of C13orf31 in intestinal inflammation.
  • HLA specific memory B cells in kidney transplantation.
  • Investigating the ligand for the only putative chicken lectin like NK cell receptor BNK.
  • The expression of collagen receptors by trophoblast and their role in trophoblast invasion.
  • Investigation of naïve CD4 T cell expansion mechanisms in humans.
  • Do specialised highly responsive subsets of natural killer cells confer a better prognosis in malignant melanoma patients?
  • Analysis of Recombination in Natural Killer Cell Receptor Genes.
  • Do MDV-induced T cell tumours arise from infection of T cells during antigen presentation?
  • Immune functions of B- and T-cell lymphomas: what remains of their lymphoid origin and do they react to microbial products?
  • Molecular analysis of CTL immunodeficiencies.