哮喘免疫表型.ppt

Horizontal bars represent medians. * * * * * * * * * * * * * * * Asthma Phenotypes and Macrolides- Results in the Entire Cohort Brusselle et al. Thorax 2013;177:148 Nonoesinophilic Asthma: Only (defined as blood eos 200/μl) Brusselle et al. Thorax 2013;177:148 Severe Asthma: Tiotropium Kerstjens et al. NEJM 2012 Environment and immunity: impact on asthma pathogenesis? NEJM 347:911, 2002 Epidemiological trends in infections and chronic diseases Innate and Adaptive Immunity Innate Antigen independent Pattern-Recognition Receptors Toll-like receptors (TLRs) NOD-like receptors (NLRs) Collectins (SP-A/D) Adaptive Antigen dependent T and B cells Antigen Specific Receptors TCR Toll-like Receptor Family Ig Ig - like Leucine-richdomain LeucineRich LRRCT Leucine-richrepeat C-terminaldomain TIR Toll Interleukin 1resistance TIR TLR1 762 aa TIR TLR2 766 aa TIR TLR3 881 aa TIR TLR4 816 aa LeucineRich LeucineRich LRRCT TIR TLR7 1023 aa LeucineRich LeucineRich TIR TLR8 1015 aa LeucineRich TIR TLR10 792 aa LeucineRich LRRCT LeucineRich LeucineRich LRRCT LRRCT LRRCT TIR TLR5 838 aa LeucineRich LRRCT TIR TLR9 1007 aa LeucineRich LRRCT TIR TLR6 796 aa LeucineRich LRRCT LeucineRich LeucineRich LRRCT LeucineRich LeucineRich LeucineRich LeucineRich LeucineRich LeucineRich LeucineRich LpA Ppg TLR4 APC T cell CD28 costimulation CD86 CD80 MHC TCR transcription IkB P P PPG LPS NF-κB activation TLR2 CD14 MyD88 Innate and Adaptive Immunity Lancet 358:1129, 2001 Early life exposure to farm animals reduces asthma and hay fever NY Asthma Rates: NYC Children 15 % Bronx 1996, AECOM 21-23% Hunts Point, 2006, NYC Bronx Heath Dept 38% Homeless 2007, Children Children Health Dept Percentage of asthma Location Data Source T Cell Proliferation and differentiation TH1 cell TH2 cell IFN-? TNF-? IL-15 IL-