Innate to Adaptive: Immune Defence Handling of Foot-and-mouth Disease Virus

Abstract

Immune defence against foot-and-mouth disease virus (FMDV) has been related to antibody-mediated compartments affording protection in both animal models and natural hosts. Induction of specific immune response involves B-lymphocytes recognising epitopes on the virus particle to produce specific antibody. Concomitant recognition of T-lymphocyte epitopes following antigen processing and presentation in the context of MHC class II molecules ensures stimulation of helper (Th)-lymphocytes to produce growth and differentiation factors necessary for development of the immune response. The critical players for inducing effective immune defences are the dendritic cells (DCs) - key controllers of immune defence development and responsiveness, providing essential antigen presentation to T-lymphocytes and antigen delivery to B-lymphocytes. Concerning vaccination, adjuvants inducing cytokines and chemokines will regulate trafficking and function of both DCs and local lymphocytes. Inducing high titres of virus-specific antibody can relate to protection against challenge infection, although this relationship is not absolute - animals displaying similar titres of specific antibody differ in resistance to FMDV infection. This is due to effector immunity involving more than antibody - the phagocytic system is essential for removing antibody/virus complexes and destroying the virus. Although there is less documentation on cytotoxic Tc-lymphocytes, there is also now evidence of their role in immune defence against FMDV. In this chapter, the interaction of FMDV with DCs and macrophages (MΦ) - in terms of DC handling the virus for stimulating T- and B-lymphocytes and the roles of DCs and MΦ in the protective immune defence - will be discussed together with the intricacies of specific immune defence development and functionality. Induction of immune defence will be presented from the viewpoint of (i) the immune system and the cellular interactions involved, and (ii) the virus in terms of the epitopes recognised by compartments of the immune system. Effector immunity will be presented in terms of current evidence on the functioning of both innate and adaptive (or specific) immune defences. Therein, the capacity of FMDV to modulate immune responses, and use cells of the immune defence for transport in the host will be described. Important issues pertaining to vaccine development and efficacy will be highlighted and discussed, in terms of understanding what the immune system requires for a vaccine to be efficacious.