Development and applications of murine asthma models induced by grass pollen allergens [Elektronische Ressource] : modulation of the immune response by a toll-like receptor agonist / von Barbara Fuchs

Development and applicationsof murine asthma modelsinduced by grass pollen allergens:Modulation of the immune responseby a toll-like receptor agonistVon der Naturwissenschaftlichen Fakultätder Gottfried Wilhelm Leibniz Universität Hannoverzur Erlangung des Grades einerDOKTORIN DER NATURWISSENSCHAFTENDr. rer. nat.genehmigte DissertationvonDipl.-Biol. Barbara Fuchsgeboren am 05.02.1979 in Hannover2007Referent: Prof. Dr. Dieter SteinhagenKorreferent: PD Dr. Thomas TschernigTag der Promotion: 04.07.2007vAbstractAllergicasthmaisachronicinflammatorydisease,inwhichsensitisationoccursviatherespiratorytract. It involves T-helper(Th)2-lymphocytes, mast cells and eosinophils, leading to physiologicaland structural changes in the lung, i.e. airway hyper responsiveness, restricted airflow andairway remodelling. The hygiene hypothesis points out that the absence of Th1-favouringsignals, e.g. bacterial pathogen associated-molecular patterns (PAMPs), promotes allergicsensitisation. PAMPs are sensed by a variety of receptors of the innate and adaptive immuneresponse, e.g. toll-like receptors (TLR). TLR2 is expressed on dendritic cells, which are believedto be one of the key players of initiating and maintaining immune responses. Furthermore,dendritic cells modulate immunity either to Th1- or Th2-responses, or induction of tolerance.Mycoplasma-induced immune responses are mediated via TLR2-heterodimers and prevent asubsequent allergic sensitisation.