免疫應(yīng)答過程

1、病原體微生物進(jìn)入機(jī)體后的可能遭遇到的危險(xiǎn)非特異性免疫第一道防線皮膚分泌物的殺菌作用唾液、胃液、淚液屮均有殺菌物質(zhì)溶菌酶使細(xì)菌溶解吞噬細(xì)胞吞噬病原體滅病原體a人體的三at防線皮膚和黏膜的阻擋作用黏月莫上纖毛的清掃作用（皮膚和黏膜組成）1第二道防線（白弩胞、血漿蛋白白細(xì)胞、血漿蛋白等消1等組成）非特異性免疫（先天性免疫）：特點(diǎn)：人人生來就有，不具特異性，而是對*第一道防線（非特異性免疫）第二道防線（非特異性免疫）1當(dāng)有炎癥、痛覺、變紅等反應(yīng)是增強(qiáng)了白細(xì)胞吞噬侵入病原體，也引起中性粒細(xì)胞和單核細(xì)胞從毛細(xì)血管申鉆出，進(jìn)入受傷部位0勺組織間隙；單核細(xì)胞分化為巨噬細(xì)胞吞噬、殺菌2補(bǔ)體協(xié)助吞噬細(xì)胞吞噬、殺菌

2、有兩種途徑：1.旁路激活途徑2.MBL途徑：MBL直接識別病原微生物表面的N-氨基半乳糖或甘露糖，進(jìn)而依次活化活化途徑。（P58）（可以通過SmartArt展現(xiàn)）兩種途徑最終都是形成MAC（膜攻擊復(fù)合物）通過破壞局部凝脂雙分子層形成細(xì)胞崩解。（P59）第三道防線一特異性免疫總路線：AgAPC處理一T、B細(xì)胞識別一T、B活化、增殖一效應(yīng)淋巴細(xì)胞識別入侵者過程巨騙細(xì)胞與巨噬細(xì)胞的MUG4厶rnnmhc醮恐體臥厲MHCSI合侔免疫應(yīng)答Jfl.Ki-MHC復(fù)合休移到Ir曰噬細(xì)胞表面淋巴pg舍細(xì)胞仲紿；廿動(dòng)分裂大眾的湃巴細(xì)胞與受體結(jié)細(xì)胞免疫嵌有抗原一MHC抗原-巨噬舗_復(fù)合體的巨噬細(xì)細(xì)胞（成熟的輔助T性

3、細(xì)胞I成熟的輔動(dòng)乜性細(xì)胞復(fù)有與受體結(jié)合含泌蛋白（成熟的細(xì)胞毒性T細(xì)胞曾N分化效應(yīng)細(xì)七7訂記憶細(xì)胞毒T性胞毒性T善同抗細(xì)胞細(xì)術(shù)原合抗識別尿隙.消滅液免疫過程抗原一巨噬與k受體（成熟的2B淋巴細(xì)胞處理對抗細(xì)胞外的病原體和毒素吞噬f蠶牆體_（成熟的）_活化的輔普細(xì)胞輔助T細(xì)胞助T細(xì)胞致敏性B淋巴細(xì)胞裂、外X.效應(yīng)B細(xì)胞記憶B細(xì)胞（漿細(xì)點(diǎn)相同抗原直接參弓者抗體+抗原病毒類失去寄生細(xì)胞能力菌產(chǎn)生毒素被屮和丿丿可溶性軌匚抗原凝聚被巨噬細(xì)胞喬噬卩歟免疫反應(yīng)初次注射抗原初次免疫反應(yīng)一/V朋抗休濃度變化,b為患病程度二次免疫特點(diǎn)：更快、董高、更強(qiáng)記憶細(xì)胞與二次應(yīng)答反應(yīng)初次免疫和二次免疫反應(yīng)過程中抗體濃度和患病程

4、度可以用圖表示：二次免疫反應(yīng)相同抗原再次入侵時(shí)，記憶細(xì)胞很快做岀反應(yīng),即很快分裂產(chǎn)生新的效應(yīng)B細(xì)胞和記憶細(xì)胞，效應(yīng)B細(xì)胞產(chǎn)生抗體消滅抗原，此為二次免疫時(shí)iw反應(yīng)。天然免疫參與天然免疫的分子和細(xì)胞C-reactiveproteinmannose-bindinglectinpolyanionslipoproteinslipoteichoicacidlipoarabinomannanlipopolysaccharideformylpeptidesmuramylpeptides,peptidoglycancomplementC3a,C5ahistamineicytokines=0increasedva

5、scularpermeabilitychemotaxisactivationofphagocytesadhesionofphagocytesactivationofendothelium吞噬細(xì)胞對病原體的識別和吞噬方甘露糖受體：識別微生物細(xì)胞壁糖蛋白.糖脂的甘露糖訝卜體受體Toll樣受體：識別不同病原體組分(LPS),傳遞危險(xiǎn)信號IngeshbymacrophageIgGFcR（X）C3b、C4b、C5b的氨基端和竣基端分別與靶細(xì)胞和（表達(dá)C3bR的）吞噬細(xì)胞結(jié)合促進(jìn)吞噬、殺傷。非氧依賴性殺傷機(jī)制：溶酶體酶和其他酶BacteriaPhagosomeI、Xyphagosomeandlysosom

6、eoflysozyme,proteases,defensins;productionofperoxide,superoxide,hyperchlorousacid;nitricoxide;degraaationofbacteriaReleaseofbacterialfragmentsFromAbbas,Lichtman,&Pober:CellularandMolecularImmunology.W.B.Saunders,1999,Fig.12-5氧依賴性殺傷機(jī)制：氧化酶系統(tǒng)和誘導(dǎo)型NO合酶0Phagocyteoxidase*O2ROIs尸nagosomewithingestedmicrobes

7、ArginineoOLysosomeswithenzymesnooROIsKillingofmicrobesbylysosomalenzymesinphagolysosomesKillingofextracellularmicrobesKillingofphagocytosedmicrobesbyROIsandNOFig2.412001GarlandScience吞噬細(xì)胞和NK細(xì)胞的作用PhagocytesPhagocytePhagocytosisandkillingofmicrobesMicrobes特異性免疫DC的生物學(xué)功能抗原遞呈*強(qiáng)的吞飲作用*受體介導(dǎo)的內(nèi)吞（FcR/CR/甘露肅受命）

8、*吞噬作用*表面捕獲（尸C）FcR和C3bRnonadherentGMCSFresponsive:viability,function,growth*激活初始T細(xì)胞,啟動(dòng)免疫應(yīng)答B(yǎng)淋巴細(xì)胞可通過BCR途徑和非特異性胞飲攝取抗原AntigenboundbyB-cellsurfacereceptorAntigeninternalizedanddegradedtopeptidefragmentsFragmentsbindtoMHCclassIIandaretransportedtocellsurface抗原遞呈作用BoundpeptidestransportedbyMHCclassIItothece

9、llsurfaceBacteriuminfectsmacrophageandentersvesicle,producingpeptidefragmentsBacterialfragmentsboundbyMHCclassIIinvesicles內(nèi)源原遞呈途悝MHCI+TAPonERTAP+AgonpeptideMHCI抗原肽TAP高爾基體|分泌的形式細(xì)胞!表面供T、B細(xì)胞識別Pathwayofclass MHC-associatedantigenpresentationrProteolyticdegradationofcytosolicproteinsTransportofpeptidesfr

10、omcytosoltoERAssemblyofpeptide-classIcomplexesinERSurfaceexpressionofpeptide-classIcomplexesProductionofproteinsinthecytosolCD8Proteasome/細(xì)胞毒素2膜分子表達(dá)及生物學(xué)活性發(fā)生明顯改變高表達(dá)Fasl介導(dǎo)靶細(xì)胞凋亡整合素CTL奔向炎癥部位高表達(dá)CD2/LFA-1-增強(qiáng)T細(xì)胞與靶細(xì)胞的結(jié)合力effectorTcellscanrespondtoth&rtargetcellswithoutco-stimulationRECOGNITION)PROLIFERATIOy&

11、FFERENBAnOIEFFECTORFUNCTIONCTL介導(dǎo)的細(xì)胞毒效應(yīng)效-靶細(xì)胞結(jié)合CTL的極化：CTL內(nèi)的相關(guān)細(xì)胞器全部向接處部位傾斜致死性打擊：穿孔素/顆粒酶途徑穿孔素(perforin)靶細(xì)胞壞死顆粒酶(granzyme)-靶細(xì)胞凋亡-FasL/Fas和TNF/TNFRI途徑介導(dǎo)靶細(xì)胞凋亡CTL殺傷耙細(xì)胞的機(jī)制FASPATHWAYGranzynicPerforinporeGranuleGRANULEEXOCYTOSISFATHWAYFADDInitiatorcasp;iscbssHTargetcellCTLPerforinExiracellularspaceGranzvniesAp

12、optosisFasdeathdomainsCTL窟蒲米$清冷満三、Th1細(xì)胞介導(dǎo)的細(xì)胞免疫效應(yīng)令Th1細(xì)胞對巨噬細(xì)胞的作用釋放多種細(xì)胞因子激活巨噬細(xì)胞：IFNy、CD40L誘生并募集巨噬細(xì)胞：IL-3.GM-CSF.TNF、MCP-1Th1細(xì)胞對T細(xì)胞的作用產(chǎn)生IL-2,促進(jìn)Th1和CTL增殖，放大免疫效應(yīng)。Th1輔助B細(xì)胞產(chǎn)生調(diào)理性抗體Th1對中性粒細(xì)胞的作用產(chǎn)生LT和TNFa,活化中性粒細(xì)胞，促進(jìn)其吞噬殺傷作用。EffectorfunctionsofTh1cellsMicrobes惡PCyNaiveCD4+ProliferationanddifferentiationMacrophageactivation(enhancedmicrobialkilling)LT,TNF