天然免疫與血管疾病

1、Guohaipeng Zhangjieyu microbesPAMPsPRRs在胞膜或胞質(zhì)中 形成同源或異源二聚體激活下游信號(hào)傳導(dǎo)通路宿主細(xì)胞合成I型IFN，細(xì)胞因子激活巨噬細(xì)胞NK細(xì)胞 吞噬病原微生物及殺傷被感染宿主細(xì)胞通過(guò)穿孔素和顆粒酶殺傷被感染宿主細(xì)胞抑制病原微生物在宿主體內(nèi)的繁殖，并對(duì)其清除招募巨噬細(xì)胞NK細(xì)胞 中性粒細(xì)胞，產(chǎn)生炎癥反應(yīng)抗原的識(shí)別抗原的識(shí)別信號(hào)轉(zhuǎn)導(dǎo)信號(hào)轉(zhuǎn)導(dǎo)效應(yīng)效應(yīng)PAMPsPAMPsType I interferonsType I interferons TLRsTLRsNLRsNLRsRLHsRLHsTRIF Dependent SignalingTRIF Depen

2、dent SignalingNOD1.NOD2 recruit RIP2, NOD1.NOD2 recruit RIP2, which activates NF-kB which activates NF-kB and caspase 1and caspase 1RIG-I.MDA5 recruits Cardif, RIG-I.MDA5 recruits Cardif, which, in turn, recruits IKKs to which, in turn, recruits IKKs to activate NF-kB and IRFactivate NF-kB and IRFin

3、flammatory responseinflammatory responsecell death , proIL-1bcell death , proIL-1binflammatory cytokinesIL-inflammatory cytokinesIL-6, IL-12, and TNF6, IL-12, and TNFthe induction ofthe induction of type I IFN type I IFNTAB1MD2TRIFMyD88MyD88UbC13BacteriaMALP2FlagellinYeastZymosanBacteriaLBPCD14SIGIR

4、RST2MyD88sTRIFTRAF6MyD88MyD88MyD88TRAF6TRAF6TRAF6MyD88sTriad3UEV1AECSITIRAKMToIIIPIRF8C-JunCREBTANKMyco-Bacterial19KDa ProteinUropathogenicBacteriaDNACpGENDOSOMENUCLEUSSLAM,CD80,CD83TNF,COX2,IL-18IFN-ResponsiveGenesIRF7IRF7IRF8IFN-b bIRF3MyD88IFN-a aNF-k kBPathwayTLR4TLR4TLR1TLR2TLR2TLR6TLR5TLR10TLR

5、11TLR12TLR13TLR3TLR7TLR8TLR9ViraldSRNAMyD88TRAMPGNBLPIk kBATF2LBPCD14RacRacTIRAPIk kBLPSPI3KPI3KRIP2RIP2IRAK4IRAK1IRAK2MKK7MEKK3TAK1TAB2MKK6p38JNKIKKsMKK3BTKIKKsIKKe eRIPRIP3TBK1IRAKMyD88TIRAPBTKLTALAMNF-k kBNF-k kBNF-k kBNF-k kBTIRAPLPSC 2007-2009SABAdhesion molecules chemotactic factorsntumor targ

6、et cellsNK-DC contactNK-DC contactnormalEndothelial celldysfunctionEndothelial cell activationInflammationProteolysisApoptosisAngiogenesisLipid-core and fibrouscap formationThrombosisinsult-induced damageEndothelial dysfunctionthe accumulation of lipids in the intima of arteriesadhesion moleculesmod

7、ifications by enzymes and oxygen radicalsProinflammatory particlesendothelial cellsrecruitment of monocytes T cells into the arterial walsmooth muscle cells (SMCs)chemokines and chemoattractantsfoam cellspathological basis for early atherosclerosisDifferentiate into macrophagesuptake lipidsMediated by TLR2 TLR4 and SRsthrombus andrupture-mediated complicationsvarious enzymes, activators,inhibitors bioactive mediatorsplaque destabilizationmatrix metalloproteinase (MMP)plaque destabilizationSMC apoptosisActivation of macropha