Adrian Smith

My research is focussed on understanding the basis of immunity to infectious challenge and includes studies of immune mechanisms that operate in different vertebrate species (particularly birds and mammals). I have a special interest in the mechanisms of immunity in the gut and how different subsets of T lymphocytes contribute to protective immunity. Many responses are stimulated during infection but it is clear that only a subset of the response is involved in protective immunity. A central theme of the work of my group is directed towards defining which of the induced responses and cellular interactions are effective in pathogen control.

Current projects include the comparative biology of pattern recognition receptors, TCRαβ and TCRγδ T cell biology, parasite genetics as a tool to define protective antigen-encoding loci and the mechanisms of immunity against infection. Currently our focus is on immunity to parasitic protozoa (e.g. Eimeria spp) and bacterial (e.g. Salmonella enterica) pathogens. The knowledge gained in these studies contributes to our understanding of the basic biology of immune systems, provides an integrated view of host-pathogen interactions and contributes towards development of effective immune interventions (e.g. vaccines).

The gut is a major site of residence and portal of entry for a wide range of pathogenic microorganisms including parasites, bacteria and viruses. The gut represents a specialised, structurally complex, immune compartment that is regulated differently from the non-mucosal immune system. Understanding the fundamental mechanisms by which the gut immune system discriminates pathogenic from non-pathogenic challenges and how pathogen-protective responses are mediated and controlled is a major issue. The balance between effective immune protection and immune pathology is delicate and achieved by the complex interplay of numerous immune cell types. The group employs a wide range of systems to address these fundamental aspects of immunity to infection and pathogenesis in the gut. Current work is focussed on the rapid induction of T cell responses, the mechanisms of immunity, T cell repertoires and regulation of immune memory in the gut. Practical implications include the better design of vaccines that target gut-tropic pathogens and greater ability to manipulate these responses to avoid enteric immune-mediated pathology.

A fundamental question in effective vaccine development is how to discriminate between those antigens that stimulate protective responses from those that induce ineffective responses. This is particularly problematic with antigenically complex pathogens (e.g. bacterial and parasitic diseases). Various approaches are being taken, including fine definition of the nature of the protective response and development of novel methods to identify protective antigens. One approach with the parasite Eimeria maxima (a serious gut disease of birds) is based upon parasite genetics, genetic fingerprinting and the use of selective barriers; this has identified that exchange of 5 regions of the genome between two immunologically distinct strains of the parasite are responsible for strain-specific protective immunity.

Many diseases are transmitted to humans from birds and effective control of the disease in birds is often the most appropriate approach to prevention of disease in man. Moreover, for some bird-specific diseases, vaccination would be the preferred disease control approach, especially to improve animal welfare and reduce the need for application of antimicrobial drugs to the human food chain. To do this effectively it is important to understand the similarities and differences in the immune system between birds and mammals and to use this knowledge to develop better vaccine approaches tailored for increased efficacy in birds. There are many similarities and differences in the structure and function of the immune system between birds and mammals including both adaptive (T and B cell) and innate compartments. For example, the repertoire of Pattern Recognition Receptors (PRR) in birds includes many orthologues of those found in mammals but there are also some unique molecules that define the way that birds sense infectious challenge.

Overall, the focus of the programme addresses fundamental mechanisms of immune induction, regulation and particularly immune protective mechanisms that operate against gut pathogens. Much of the work is related to the function of various T cell compartments in the gut environment with broad implications for both human and animal health.