Infection and immunity
Infectious diseases remain a major cause of mortality and morbidity throughout the world and their occurrence often represents a failure of the immune system to effectively combat the infectious agent. Therefore we need to understand better how microbes interact with their host cells and cause disease and how these interactions often permit microbes to escape from immune control. Immunology itself also impinges on a wide range of other aspects of clinical and basic science and it underpins development of therapeutic approaches to non-infectious diseases, including autoimmune diseases and other conditions ranging from cancer to dementia.
Research in infection is sub-divided into the interdisciplinary themes of virology, bacteriology and parasitology. The emphasis is on the understanding of invasion and transmission, including diseases and parasites particularly relevant to developing countries such as trypanosomiasis, salmonella, malaria, schistosomiasis and leishmaniasis; and the molecular biology and pathogenesis of herpesviruses, HIV, rotaviruses, influenza and papillomavirus. Research on animal infection is underpinned by the Cambridge Infectious Diseases Consortium (CIDC), which was formed by the University of Cambridge together with The Animal Health Trust in Newmarket and other national centres for animal diseases to create a world-class research environment for the future training of veterinarians as infectious disease specialists. There is now a broader virtual organisation, Cambridge Infectious Disease.
Virology research covers a broad range of viral pathogens of importance to man and economically significant animals. It includes studies on virus entry; assembly and exit; transcriptional and translational control of viral gene expression; immune control of virus infection; viral pathogenesis and genomics. Research on mathematical modelling of viral disease also involves the Department Applied Mathematics and Theoretical Physics. Research programmes include herpes viruses, influenza, HIV, rotaviruses and papillomaviruses.
Bacterial infections cause diseases such as tuberculosis, which is rife in the developing world and re-emerging in Western countries. Infections in domestic animals (for example with Campylobacter or Salmonella) pose a threat to humans and cause great losses to the food industry. The increase in antibiotic resistance is making bacterial infection more difficult to treat so new rational approaches for prevention and treatment are urgently needed. Molecular and cellular work includes the mechanisms of disease caused by bacteria, antibiotic resistance, membrane transport mechanisms, protein trafficking and bacterial motility and invasion. Advanced imaging techniques and cell biology also support research on pathogenesis of infection. This research greatly benefits from the integration of biological and mathematical modelling approaches allowing the analysis of bacterial spread and distribution within infected cells in the host tissues and between individuals in human and animal populations. The sequencing of the genomes of a number of bacterial pathogens has been achieved.
Parasites continue to impose a major health and economic burden on the developing world. Work in parasitology focuses on diseases that affect humans such as schistosomiasis and infection with trypanosomes and Toxoplasma gondii. Prevention of infections requires an understanding of the epidemiology of the disease (spread, transmission); this is especially complex in parasites and typically involves two or more host species (e.g. mosquitos and man). Safe, protective and cost effective vaccines would be of great benefit. Research directed towards parasites integrates basic molecular biology, cell biology and biochemistry, functional genomics, bioinformatics, human epidemiological investigations and vaccine immunology. Field-based epidemiology and laboratory-based experimental models are also used to evaluate human immune response to chronic parasitic infection.
Studies of the immune system in health and disease lead to advances in understanding the mechanisms of immunity to infection and the role of the immune system in autoimmune diseases such as diabetes, multiple sclerosis and rheumatoid arthritis and the vasculitides. An understanding of the genes, molecules and cells of the immune system has led to developments in biotechnology, vaccine research, cancer therapy, and the treatment of infectious diseases, allergy, immune deficiency, autoimmunity and cancer. Research in immunity can be divided into three broad areas: fundamental biology of both the innate and adaptive immune response; immunity in infectious diseases; autoimmunity, rheumatology and transplantation immunology.
The biology and genetics of the innate and adaptive immune response is a major research area. Research on immunoglobulins is focused on understanding gene transcription and hypermutation and engineering immunoglobulins for therapeutic and diagnostic purposes. The organisation, polymorphisms and disease associations of receptor families involved in natural and T cell mediated immunity are also under investigation. The innate immune system is the first line of defence in immunity to infection and cancer and involves the natural killer (NK), myeloid and other cell types. NK cell biology and the genomic organisation of NK receptors in relation to health and disease are active and expanding research areas. The biology of dendritic cells and their innate receptors is studied at both the cellular and molecular level. Fundamental studies on the regulation of immune cell activation and of immune regulation through complex cellular interactions are also major areas of research.
Immunity to infection is an expanding area of research. A wide range of organisms (viruses, bacteria and parasites) and their interactions with the host immune system are currently being investigated. This research has implications for disease pathogenesis, vaccine design and autoimmunity. The interaction of immunity and the pathogenic organism within chronic and persistent infections is a particularly significant theme. There is a focus on the pathogenesis of persistent viruses such as herpes viruses and lentiviruses and development of vaccine strategies for immunity to persistent viruses in naturally occurring models of viral infections of domestic animals. Parasitic infections are typically very long-lived. The complex immuno-biological interrelationships between host and parasite are being investigated. In many parasitic diseases the immune system plays a significant role in their pathology (damaging effects). Current studies include host/parasite relationships involving schistosomes, kinetoplastids (e.g. trypanosomes) and apicomplexans (e.g. Toxoplasma gondii). These studies also includes the analysis of global pathogen gene expression and function within the hosts and in the environment, the study of the interactions between bacterial genes and the immune system. How viruses, parasites and bacteria subvert the immune response is a major strength of infection and immunity research at Cambridge and this links with studies on immunity to pathogens and autoimmune disease.
The genetics and mechanisms of autoimmunity are major thematic areas. The role of T cells in causing autoimmune diseases and the potential for specific targeting to halt autoimmune pathology is being studied in a range of conditions. Animal models of autoimmune diabetes are a particular focus. Major programmes are focussed on immune mechanisms leading to failure of self tolerance and tissue destruction and on the analysis of genetic susceptibility to diabetes. Basic, clinical and translational research in autoimmune diseases such as multiple sclerosis and arthritis is an active area. Transplantation immunology is another area and the availability of strong histopathological expertise underpins clinical immunological research. Recently the virtual Cambridge Immunology organization has been founded.