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Infection and immunity

Infectious diseases; immunology; autoimmunity; microbiology; bacteriology, virology, parasitology; epidemiology and mathematical biology

 

This extraordinarily important theme is now reflected in four University strategic initiatives and networks with other centres of global significance funded in the last few years. There are programmes to study infectious diseases of humans, animals and plants, many of which disproportionately affect the developing world. A wide range of research involving viruses, bacteria, parasites and other pathogens is complemented by work in immunology of relevance to non-infectious disease and non disease states.

There are very strong links between basic and clinical research in humans and animals and key networks involving Physical Sciences, especially mathematics. In recent years this work has increasingly become embedded in Biological Sciences departments themselves and mathematical training of our research students is being fostered in new PhD programmes. A small sample of recent work is highlighted here.

Work continues on genome sequencing and other studies of bacteria important in disease. We have developed further understanding of diseases such as bovine tuberculosis and have made important advances in dealing with human meningitis in Africa. Animal to human transmission of a new type of MRSA (methicillin-resistant Staphylococcus aureus) has been identified and important new testing methods have been developed.

Characterization of a bacterial 'altruistic' anti-phage mechanism has led to understanding of how bacteria themselves avoid a viral infection spreading through their population. In the longer term this finding could help the development of new anti-bacterial drugs.

Key insights have been obtained into the mechanisms of the spread of infection, within and between hosts, by pathogens. Work includes detailed molecular and phylogenetic analyses, antigenic cartography, structural and epidemiological modelling. Pathogens include viruses that may infect domesticated animals and birds and humans. Work on potential pandemics has received much media attention and there is a new World Health Organization (WHO) Collaborating Centre devoted to emerging infectious diseases.

Some recent examples of epidemiological studies include modelling of host-virus evolution to predict the likelihood of development of mammal-to-mammal transmissible H5N1 avian influenza A strains.  Stochastic, spatio-temporal models have been coupled with economic models to predict plant disease spread and effectiveness of control at landscape and regional scales. A theoretical framework to identify epidemiological effectiveness of biological control of fungal pathogens has been developed. All this work is heavily dependent on computation and mathematics.

Immunology and autoimmunity

Immunology is of key importance in understanding resistance to infection and susceptibility to chronic autoimmune diseases. It is becoming of interest in other conditions including cancer, reproduction and neurological disorders. The School has made important advances in functions of HLA (human leukocyte antigen) class I and class II molecules an dtheri receptors. HLA class I has been found to be involved in control of pregnancy as well as HIV. Important conceptual frameworks have been developed  that explain how the MHC (major histocompatibility complex) of non-mammalian vertebrates work. Models for the autoimmune diseases such as type-1 diabetes have been developed. Research showed that protection from diabetes arises through an interaction between the infectious agent and the innate immune system such that circuits which regulate the autoimmune response are reinforced. Pioneering work showed that TRIM21 is a potent Fc receptor leading to the important new concept of antibody-dependent intra-cellular neutralisation. Work on pattern-recognition receptors has led to new understanding of human allergic response to cats. Another area where Cambridge has strength is in the identity and function of receptors/co-receptors and signalling pathways in T-cells and the way in which alterations in these pathways lead to disease states including autoimmunity. The innate immune system has evolved to provide the first line of defence against invading pathogens. We are also interested in how pathogens have overcome these innate immune mechanisms by developing their own potent inhibitors of the host signalling mechanisms.