Intervention in established immune responses by feeding protein antigens

[摘要] The gastrointestinal (GI) tract is exposed continuously to a variety of foreign antigens that range from soluble dietary proteins to numerous pathogens and is thus the major site of antigenic challenge in the body. Whereas infection with a mucosal pathogen results in an active primary immune response followed by memory to subsequent exposure, oral administration of soluble antigens results in a suppressed response to subsequent systemic exposure to the antigen. This phenomenon is termed oral tolerance and its physiological role may be to prevent food hypersensitivities. In addition it may provide a potent therapy for a variety of autoimmune and inflammatory disorders. However, oral tolerance is also a major obstacle to the development of oral vaccines. Although there is a substantial amount of evidence that suggests that suppression of autoimmunity by orally administered antigen is a feasible and therapeutic option, most existing studies of oral tolerance have explored the mechanisms responsible for the ability of fed antigen to prevent subsequent systemic immune responses in previously naive animals. Little is known about the mechanisms which determine the induction of oral tolerance in the primed immune system. Thus the aims of my studies were to define feeding regimes for inducing optimal oral tolerance in primed mice, to establish the effects of feeding antigen to primed mice on a variety of parameters of systemic immunity in vivo and in vitro and to investigate the mechanisms of oral tolerance in primed mice. I used a model antigen in my studies so that I could exploit experimental systems already developed in the laboratory for the induction and assessment of oral tolerance to OVA in naive mice. Thus I examined a variety of antigen doses administered at different times after priming with OVA/CFA and investigated the scope of responses influenced by the tolerance.

[发布机构] University:University of Glasgow

[关键词] Immunology