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Immunology

 

Introduction

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

2016-2017
  • The function of PI3K signaling in the placenta.
  • Characterisation of follicular helper T cells in chronic allograft rejection.
  • The Role of Saposin Proteins in Lipid Antigen Presentation.
  • The role of linear ubiquitin chains in the innate immune responses to nucleic acids.
  • Characterisation of components of the MHC class I antigen presentation pathway in chronic liver disease.
  • KIR and adult onset type 1 diabetes.
  • Does STING play a role in responses to atherosclerosis relevant stimuli?
  • Using peptide-MHC libraries to identify T cell epitopes from econimically-important chicken pathogens.
  • Investigation of the effects of inhibitory signals and their blockage in cytotoxic T lymphocytes.
  • Comparison of chicken Vbeta1 and Vbeta2 T-cell receptors.
  • How is offspring immunity set during development?
  • Regulation of gammadelta T cells by butyrophilin/BTN proteins.
  • Uterine Innate Lymphoid Cells
  • Modelling endometrial cancer using CRISPR-Cas9 on human endometrial glandular organoids.
2015-2016
  • The Short-Term Effects of PD-1 on T-Cell Degranulation and Cytotoxicity
  • Investigating the role of maternal NK lectin-like receptor NKG2C in pre-eclampsia.
  • A Role for TAPBPR in HLA-B27 Biology:  Implications for Spondyloarthropathies.
  • The Role of GSK-3 in PD-1 Down-Regulation in Viral and Cancer Immunotherapy.
  • Synthesis of Chicken MHC Class II-Peptide Oligomers to Study Marek's Disease Virus Infection.
  • Investigating the role of CD4+ T cells in the breaking of HEL-specific tolerance in a chimeric mouse model.
  • Elucidating the signalling pathways that drive interferon transcription during Herpes simplex virus type 1 (HSV-1) infection.
  • TSLP signalling in human monocyte derived dendritic cells regulates HIP-1α via ROS.
  • Development of a Cervical Organoid Culture Model for Studying Human Papillomavirus Pathogenicity.
  • Does HLA-A and HLA-B have a role in regulating HLA-C surface expression?
  • Regulation of human gd T cells by the BTN3A-dependent phosphoantigen-sensing mechanism.