Bovine immunopathogenesis

Vaccination is based on the generation of immunological memory through the exposure of an individual to an attenuated form of a disease-inducing micro-organism (pathogen). Upon exposure to the pathogen, vaccinated individuals react faster against the pathogen than non-vaccinated individuals. However, not all immune responses are protective against infection; indeed, some responses may contribute to disease development. A major interest of the group is the distinction between protective and disease-inducing responses. We are currently doing laboratory and animal studies to characterise the protective immune responses induced by the BCG tuberculosis (TB) vaccine.

We have found that vaccination with BCG induces T-cells that produced molecules involved in the killing of TB mycobacteria in the laboratory (Figure 1) and in the standing animal (Figure 2). In collaboration with Dr. Martin Vordermeier and Prof. Glyn Hewinson of the Veterinary Laboratories Agency we are also testing the protective efficacy of prime-boost vaccination regimens as currently being tested in humans. The protective efficacy of these regimens will be related to the immune responses induced. These experiments will help develop correlates of immunity to TB and may contribute not only to the development of safer vaccines but also to the development of improved diagnostics responses

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Related research can be found on these pages:

  • Molecular aspects of the interaction of mycobacteria with bovine antigen presenting cells.
    Tracey Coffey, Genomics and Post-Genomics Group
  • The bridging of the interaction of antigen presenting cells and other cells of the innate immune response, such as natural killer cells and cells of the adaptive immune system, such as g/ d T-cells
    Jayne Hope, Innate and Adaptive Immune Mechanisms

Publications:

  • Endsley, JJ, Hogg, A, Shell, LJ, McAulay, M, Coffey, T, Howard, C., Capinos-Scherer CF, Waters, WR, Nonnecke, B, Estes, DM and Villarreal-Ramos, B. (2007). Mycobacterium bovis BCG vaccination induces memory CD4+ T cells characterized by effector biomarker expression and anti-mycobacterial activity. Vaccine. [in press] . 
  • Villarreal-Ramos B, Reed S, McAulay M, Prentice H, Coffey T, Charleston BC, Howard CJ. (2006) Influence of the nature of the antigen on the boosting of responses to mycobacteria in M. bovis-BCG vaccinated cattle. Vaccine. 24(47-48):6850-8. [Abstract]. 
  • Thom ML, Hope JC, McAulay M, Villarreal-Ramos B, Coffey TJ, Stephens S, Vordermeier HM, Howard CJ. (2006). The effect of tuberculin testing on the development of cell-mediated immune responses during Mycobacterium bovis infection. Vet Immunol Immunopathol. 114(1-2):25-36. [Abstract]. 
  • Widdison S, Schreuder LJ, Villarreal-Ramos B, Howard CJ, Watson M, Coffey TJ. (2006) Cytokine expression profiles of bovine lymph nodes: effects of Mycobacterium bovis infection and bacille Calmette-Guerin vaccination. Clin Exp Immunol. 144(2):281-9. [Abstract]. 
  • Thom M, Morgan JH, Hope JC, Villarreal-Ramos B, Martin M, Howard CJ. (2004). The effect of repeated tuberculin skin testing of cattle on immune responses and disease following experimental infection with Mycobacterium bovis. Vet Immunol Immunopathol. Dec 28;102(4):399-412.  
  • Villarreal-Ramos, B., McAulay, M., Chance, V., Martin, M., Morgan, J. and Howard, C. J. (2003). Investigation on the role of CD8+ T-cells in immunity to bovine tuberculosis in vivo. Infect. Immun. 71(8): 4297-4303. [Abstract].