Principal areas of research
Enteric Immunology to infectious challenge, T cell biology, discovery of protective antigens, mammalian and avian immune mechanisms, avian Toll-like Receptors.

Biography
Dr Smith was awarded a PhD in the field of immunology to parasites by the University of Nottingham in 1994. Subsequently, Dr Smith worked with Professor Hayday (Biology Department, Yale University, USA) as a Postdoctoral Research Associate and Research Fellow focussed on gut infection and the biology of TCRgd+ T cells. In 1997 Dr Smith moved back to the UK and established the Enteric Immunology Group at the Institute for Animal Health, based on the Compton site. In 2008 Dr Smith joined the Department of Zoology at the University of Oxford where he will continue to work in vaccine-related fields and closely with his former colleagues at IAH. The work of the group is focused on fundamental cellular and molecular immunology of the gut (especially to infectious challenge) and includes aspects of vaccine development in birds and mammals.

Research
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.

Key publications
Pennington, D. J., B. Silva-Santos, T. Silberzahn, M. Escorcio-Correia, M. J. Woodward, S. J. Roberts, A. L. Smith, P. J. Dyson, and A. C. Hayday. 2006. Early events in the thymus affect the balance of effector and regulatory T cells. Nature 444:1073-1077.

Blake, D. P., M. W. Shirley, and A. L. Smith. 2006. Genetic identification of antigens protective against coccidia. Parasite Immunol 28:305-314.

Blake, D. P., P. Hesketh, A. Archer, M. W. Shirley, and A. L. Smith. 2006. Eimeria maxima: the influence of host genotype on parasite reproduction as revealed by quantitative real-time PCR. Int J Parasitol 36:97-105.

Beal, R. K., C. Powers, T. F. Davison, P. A. Barrow, and A. L. Smith. 2006. Clearance of enteric Salmonella enterica serovar Typhimurium in chickens is independent of B-cell function. Infect Immun 74:1442-1444.

Kwa, S-F., Peter Beverley and Adrian L. Smith 2006 Peyer’s patches are required for the induction of rapid Th1 responses in the gut and mesenteric lymph nodes during an enteric infection J. Immunol. 176: 7533-7541

Philbin, V. J., M. Iqbal, Y. Boyd, M. J. Goodchild, R. K. Beal, N. Bumstead, J. Young, and A. L. Smith. 2005. Identification and characterization of a functional, alternatively spliced Toll-like receptor 7 (TLR7) and genomic disruption of TLR8 in chickens. Immunology 114:507-21.

Back to main Investigators page