Induction of Tolerance via the Respiratory Mucosa

Abstract

Immunological tolerance is defined as a state of specific non-responsiveness to a particular antigen induced by previous exposure to that same antigen. The mucosal surfaces comprise the upper and lower respiratory tracts, the gastrointestinal tract and the urogenitary tract, and are a major site of antigenic challenge. The immune system associated with the mucosa has the extraordinary potential to discriminate between antigens that are harmless (e.g. inhaled and dietary antigens) and those that are associated with pathogens. Normally soluble proteins delivered through the mucosal surfaces do not elicit a strong systemic immune response but instead induce a transient local immune response that is replaced by long-term peripheral unresponsiveness – this is termed mucosal tolerance. The phenomenon of oral tolerance is well established and considerable attention has focussed on defining the underlying mechanisms. However, only comparatively recently was the induction of tolerance via the respiratory mucosa described, and it is this form of mucosal tolerance which forms the basis of this review.

Meningococcal Outer Membrane Vesicle Vaccine Given Intranasally Can Induce Immunological Memory and Booster Responses without Evidence of Tolerance

“…Normally, soluble proteins may induce a state of immunological tolerance when administered onto mucosal surfaces (16). However, we found no evidence that the particulate protein vaccine used i.n.…”

Escherichia coliHeat-Labile Enterotoxin B Subunit Is a More Potent Mucosal Adjuvant than Its Closely Related Homologue, the B Subunit of Cholera Toxin

“…EtxB was found to be a more potent adjuvant than CtxB, stimulating responses to hen egg lysozyme when the two were coadministered to mice intranasally, as assessed by enhanced serum and secretory antibody titers as well as by stimulation of lymphocyte proliferation in spleen and draining lymph nodes. These results indicate that, although structurally very similar, EtxB and CtxB have strikingly different immunostimulatory properties and should not be considered equivalent as prospective vaccine adjuvants.Oral or nasal mucosal administration of protein antigen is thought to favor a state of immunological unresponsiveness by a process of peripheral tolerance, in order to avoid activation of detrimental immune responses to innocuous dietary and airborne environmental antigens (11,23). Cholera toxin (Ctx) and heat-labile enterotoxin (Etx) from enterotoxinogenic strains of Escherichia coli, however, are strongly immunogenic by both parenteral and mucosal routes and elicit strong antitoxin antibody responses when administered either orally or nasally (reviewed in reference 21).…”

“…Oral or nasal mucosal administration of protein antigen is thought to favor a state of immunological unresponsiveness by a process of peripheral tolerance, in order to avoid activation of detrimental immune responses to innocuous dietary and airborne environmental antigens (11,23). Cholera toxin (Ctx) and heat-labile enterotoxin (Etx) from enterotoxinogenic strains of Escherichia coli, however, are strongly immunogenic by both parenteral and mucosal routes and elicit strong antitoxin antibody responses when administered either orally or nasally (reviewed in reference 21).…”

Stimulation of Mucosal and Systemic Antibody Responses against Recombinant Transferrin-binding Protein B of Actinobacillus pleuropneumoniae with Chitosan after Tracheal Administration in Piglets

“…Most antigens delivered mucosally are poorly immunogenic and can induce immunological tolerance [16]. This study found that nasal administration of rTbp B without chitosan induced very weak immune responses.…”