免疫缺陷性疾病課件

HIV的致病機(jī)制9免疫缺陷性疾病ImmunodeiciencyDiseasesChapterVIIII9免疫缺陷性疾病一、概念：免疫缺陷?。▇disorders）：免疫系統(tǒng)中任何一個(gè)環(huán)節(jié)或其組分因先天發(fā)育不全或后天各種因素所致?lián)p害，使免疫活性細(xì)胞的發(fā)生、分化、增殖和代謝異常而引起的免疫功能不全綜合征。9免疫缺陷性疾病9免疫缺陷性疾病9免疫缺陷性疾病常見的原發(fā)性免疫缺陷性疾病TB9免疫缺陷性疾病1、原發(fā)性B細(xì)胞缺陷病：某種原因使B細(xì)胞發(fā)育停滯→先天性B細(xì)胞缺乏或分化成熟障礙。9免疫缺陷性疾病B細(xì)胞發(fā)育過程VHDHJHVLJLIgM

不成熟B細(xì)胞DHJHB220B祖細(xì)胞IgDIgM

成熟B細(xì)胞替代輕鏈前B細(xì)胞9免疫缺陷性疾病MDMM不成熟B細(xì)胞ImmatureBcellsM

前B細(xì)胞（胞漿出現(xiàn)IgM重鏈）Pre-Bcells

祖B細(xì)胞Pro-BcellsMDGMDA

成熟B細(xì)胞MatureBcells9免疫缺陷性疾病IgmVpre-Bl5Ig-a/Ig-bLyn，F(xiàn)yn，Blk，Btk，Syk信號(hào)轉(zhuǎn)導(dǎo)Pre-BCR前B細(xì)胞首先開始表達(dá)Igm

鏈，在k或者l輕鏈基因發(fā)生重排并表達(dá)之前，Igm

鏈與替代輕鏈l5和Vpre-B以及Iga/b共同組成Pre-BCR表達(dá)于細(xì)胞的表面。Iga/b執(zhí)行信號(hào)轉(zhuǎn)導(dǎo)功能。9免疫缺陷性疾病B細(xì)胞發(fā)育障礙或者缺乏T細(xì)胞幫助均可導(dǎo)致體液免疫應(yīng)答缺陷。臨床表現(xiàn)為反復(fù)的胞外寄生菌感染。9免疫缺陷性疾病原發(fā)性B細(xì)胞免疫缺損IgA漿細(xì)胞淋巴干細(xì)胞XLAbtk基因突變前B細(xì)胞sIgMTTTTTXHLMCD40L基因缺陷成熟細(xì)胞IgG/IgA/IgM/IgD/IgEB記憶細(xì)胞IgA

選擇性IgA缺陷？AGMBBB漿細(xì)胞CVID9免疫缺陷性疾病(1)性聯(lián)無免疫球蛋白血癥（XLA）Bruton病a1a2bg白蛋白球蛋白（a）（b）（c）X-linkedagammaglobulinemia,9免疫缺陷性疾病XLAbtk基因突變淋巴干細(xì)胞前B細(xì)胞sIgMBruton’styrosinkinase,BtkBruton酪氨酸激酶9免疫缺陷性疾病9免疫缺陷性疾病染色體水平：X染色體長臂q21.3-22多基因缺陷轉(zhuǎn)錄水平：B細(xì)胞Ig重鏈重排正常，但I(xiàn)g的輕鏈基因重排和表達(dá)有缺陷細(xì)胞水平：B細(xì)胞不能發(fā)育成熟表現(xiàn)：外周血或淋巴組織中B細(xì)胞很少或缺如，淋巴結(jié)很小，無生發(fā)中心，無漿細(xì)胞，扁桃體缺如，血清中多種Ig水平很低或測不出，但T細(xì)胞數(shù)目和功能基本正常。癥狀：反復(fù)化膿性感染性聯(lián)低丙球蛋白血癥9免疫缺陷性疾病Brutonagammaglobulinemia.Thispatientpresentedwithrecurrentotitis(耳炎)andareasofcellulitis（蜂窩織炎）inthediaperarea.PseudomonasaeruginosaandStaphylococcusaureuswereisolatedfromtheskinlesions.Autoimmunehemolyticanemiaandautoimmuneneutropenia（中性粒細(xì)胞減少癥）wereconfirmedbythepresenceofautoantibodies.Thepatienthasamutationonexon15,A504T,whichchangedanasparagine（天冬氨酸）residuetoavaline（纈氨酸）residue.9免疫缺陷性疾病Picture2.Brutonagammaglobulinemia(ie,X-linkedagammaglobulinemia[XLA])inbrothers.XLAwasdiagnosedintheless-robustyoungerbrotherwhenhepresentedwithneutropeniaandtyphlitis.Theolderbrother,withahistoryof7episodesofpneumonia,wasthenevaluatedandgiventhediagnosisofXLA.InbothbrothersCD19-Bcellswerelessthan1%;thisfindingisconsistentwithXLA.9免疫缺陷性疾病(2)性聯(lián)高IgM血癥（XLHM）性聯(lián)遺傳病：X染色體上CD40L基因突變IgG、IgA和IgE重鏈類別轉(zhuǎn)換有障礙表現(xiàn)：IgG和IgA血清濃度極低，反復(fù)細(xì)菌胞外感染。IgMJ鏈X-linkedhyperimmunoglobulinMsyndrome9免疫缺陷性疾病前B細(xì)胞sIgMTTTTTXHLMCD40L基因缺陷成熟細(xì)胞IgG/IgA/IgM/IgD/IgE9免疫缺陷性疾病XLHM患者淋巴小結(jié)的特點(diǎn)正常生發(fā)中心XLHM淋巴小結(jié)B細(xì)胞活化受阻記憶性B細(xì)胞B細(xì)胞大量凋亡IgM未活化B細(xì)胞IgMIgMT細(xì)胞不表達(dá)CD40LT細(xì)胞表達(dá)CD40L9免疫缺陷性疾病輔助性T細(xì)胞幫助B2細(xì)胞活化12CD40/CD40LB細(xì)胞Th細(xì)胞TD抗原CD49免疫缺陷性疾病ThB7MHC-IITCRCD4ICAMLFA-1APCThThBCD40LCD40分泌細(xì)胞因子ThBBBTh細(xì)胞活化、增殖B細(xì)胞擴(kuò)增漿細(xì)胞BCR抗原TD抗原誘導(dǎo)體液免疫應(yīng)答的過程BmCD289免疫缺陷性疾病IgClass(Isotype)SwitchingPlasmacellsIgMIgEorIgG2IgAorIgG2bIgG2orIgG3IgM/IgDActivatedBcell(centroblast)ProliferatingBcell(centrocytes)ProliferationcytokinesIL-2,IL-4,IL-5DifferentioncytokinesIL-2,IL-4,IL-5,IFN-

,TGF-

IL-2IL-4IL-5IL-2IL-4IL-5IL-4IFN-

TGF-

9免疫缺陷性疾病CD40LBMThymiccellCD40Lknockout(mimickinghumanX-linkedhyperIgM)RetroviralvectorCD40LLowexpression9免疫缺陷性疾病CVID:commonvariableimmunodeficiency普通變化型免疫缺陷病,為IgA,IgG缺陷(3)選擇性IgA缺陷或IgA和IgG缺陷AGMBBB漿細(xì)胞CVIDJ鏈分泌鏈IgAdimer9免疫缺陷性疾病Endoscopicimagingoftheduodenumshowsmultipleprominentnodules3–5mminsize,consistentwithnodularlymphoidhyperplasia9免疫缺陷性疾病常染色體顯/隱性遺傳病或胚胎期風(fēng)疹病毒感染/藥物造成的畸變。細(xì)胞水平：表達(dá)IgA的B細(xì)胞不能分化成分泌IgA抗體的漿C。表現(xiàn)：僅IgA缺陷而IgM和IgG水平正常。癥狀：IgA低→呼、消、泌尿生殖粘膜感染。選擇性IgA缺陷9免疫缺陷性疾病2、原發(fā)性T細(xì)胞缺陷癥Thissyndromewasdescribedinthe1960s.Itisageneticconditionandsothereareoftenseveralpeopleinthefamilyaffected.Theunderlyingproblemisamissingportionofthe22ndchromosome.9免疫缺陷性疾病

胚胎三、四咽囊發(fā)育障礙→先天胸腺發(fā)育不良，伴隨甲狀旁腺、主動(dòng)脈弓、唇、耳發(fā)育不良細(xì)胞水平：T細(xì)胞不能成熟（隨年齡增長T細(xì)胞能在胸腺外成熟）表現(xiàn)：血中Tcell缺乏，細(xì)胞免疫缺陷癥狀：易患病毒、真菌感染，移植物抗宿主反應(yīng)，自身免疫病，惡性腫瘤(1)先天性胸腺發(fā)育不全（DiGeorge綜合癥）9免疫缺陷性疾病FuneralHeldFor2-Year-OldHeart-ConditionVictim9免疫缺陷性疾病

SkeletalpreparationsfromwildtypeandTbx1mutantembryos.Themutantembryoontherighthasabnormalitiesinthepharyngeal(咽的)arch-derivedskeletalstructuresinthehead.ThismutantprovidesamousemodelofthehumanDiGeorgesyndrome9免疫缺陷性疾病

BacktoFISHInformationprintMetaphaseFISHExamples

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ThisisanexampleofametaphasecellthathasbeenhybridizedwiththeprobeforDiGeorge/Velo-Cardio-Facial/CATCH22/Shprintzensyndromewhichiscausedbyamicrodeletiononchromosome22.Theprobeinthisparticularcaseisadual-colormixtureoftwoseperateprobesforchromosome22.Thegreensignalisaninternalcontrolandislocatedat22q13.Itallowsforquickidentificationofboth#22chromosomes.TheredsignalislocatedattheDiGeorgeregionat22q11.2.Sinceboth22'shavetheredsignalinthiscellthereisnotamicrodeletionwithintheDiGeorgeregionandthispatientwouldnothaveDiGeorgesyndrome.

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Thismetaphasehasbeenhybridizedwitha"painting"probeforchromosome4whichcausestheentirechromosometofluoresce.Onechromosome4fromthispatientwasabnormalbutitwasdifficulttodeterminefromroutineCytogeneticsifithadasmallterminaldeletionat4qorwastheresultofamorecomplexrearrangement.Sinceboth4'sarefluorescentalongtheirentirelengthandnofluorescentmaterialispresentonanyotherchromosome,thissuggeststhattheabnormalityisasmallterminaldeletion.Themetaphasebelowisfromthesamepatientandfurtherconfirmsthisdiagnosis.

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Thismetaphasefromthesamepatientasthecellabovehasbeenhybridizedwithaprobefortheterminalpartofchromosome4q.Sincethereisonlyonegreensignalthisconfirmsthatonechromosome4ismissingmaterialfromtheterminalendof4q.ThiscaseisagoodexampleofhowroutineCytogeneticsandFISHcanbeusedtogethertoaccuratelydiagnosesubtlechromosomeabnormalities.

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ThisisanexampleofametaphasecellthathasbeenhybridizedwiththeprobeforSteroidSulfataseDeficiencywhichiscausedbyamicrodeletionontheXchromosome.TheprobeinthisparticularcaseisamixtureoftwoseperateprobesfortheXchromosome,bothredincolor.The"Xcen"probesignalisaninternalcontrolandislocatedattheXcentromere.ItallowsforquickidentificationoftheXchromosome(s).The"Xp22.3"probesignalislocatedattheSteroidSulfataseregionatXp22.3.SincetherearetwoXchromosomesandonlyonehastheSteroidSulfatasegenesignal,thisindividualisafemalecarrierforSteroidSulfataseDeficiency.

ThisisametaphasecellthathasbeenhybridizedwiththeprobeforDiGeorgewhichiscausedbyamicrodeletiononchromosome22.Theprobeisadual-colormixtureoftwoseperateprobesforchromosome22.Thegreensignalisaninternalcontrolandislocatedat22q13.Itallowsforquickidentificationofboth#22chromosomes.TheredsignalislocatedattheDiGeorgeregionat22q11.2.Sinceboth22'shavetheredsignalinthiscellthereisnotamicrodeletionwithintheDiGeorgeregionandthispatientwouldnothaveDiGeorgesyndrome.9免疫缺陷性疾病PatientwithDiGeorgesyndromeDepletedthymus-sependentarea(TDA)smallprimaryfolicles(PF)Normalsubject:ThepopulatedT-cellareathewell-developedsecondaryfoliclewithitsmantleofsmalllymphocytes(M)Germinalcenter(GC))9免疫缺陷性疾病無胸腺的裸鼠是T細(xì)胞選擇性缺陷的天然動(dòng)物模型Athymic,ornude,mouse(nu/nu:onchromosome11)Thisdefectleadstoabsenceofthethymusoravestigialthymusandcell-mediatedimmunodificiency.Cannoteasilysurvive,mortality:100%within25weeks;50%within2weeksafterbirth.9免疫缺陷性疾病AthymicnudemicearekeptbehindabarrierwithHEPAfilteredair;autoclavedfee,bedding,waterandcages.Aresearchassistantusesasepticprocedurestoprotectthesemicefromorganismsintheenvironment9免疫缺陷性疾病TumorsformedbyRat1cellsexpressingmyr-p110.Nudemicewereinjectedontheleftflankwith1X106Rat-1Acellsexpressingmyr-p110andontherightflankwithanequalnumberofcontrolRat-1Acells.Thispicturewastaken10dayspostinoculation.Practicalexperimentaluses:Hybridomasorsolidtumorsfromanyoriginmaybegrownin9免疫缺陷性疾病(2)TCR信號(hào)轉(zhuǎn)導(dǎo)障礙9免疫缺陷性疾病激酶鏈的信號(hào)整合轉(zhuǎn)錄因子被活化早期基因IL-2基因IL-2Ra基因T細(xì)胞活化的信號(hào)轉(zhuǎn)導(dǎo)fynPLCCa++ZAP-70CD4TCRLCKPI-3kHLA表達(dá)障礙IL-2生成障礙9免疫缺陷性疾病ITAM:Immunoreceptortyrosine-basedactivationmotifsCD3

鏈缺陷,TCR-CD3表達(dá)水平降低CD3

鏈缺失,T細(xì)胞活化缺陷9免疫缺陷性疾病3、原發(fā)性T、B細(xì)胞聯(lián)合免疫缺陷病Achildwithseverecombinedimmunodeficiencyshowingskinlesionsduetoinfectionwithvacciniagangrenosumresultingfromsmallpoximmunization.Lesionswerewidespreadoverthewholebody.9免疫缺陷性疾病嚴(yán)重聯(lián)合免疫缺陷病染色體水平：2號(hào)染色體上腺苷脫氨酶（ADA）基因缺陷或突變14號(hào)染色體上嘌呤核苷磷酸化酶（PNP）基因缺陷或突變性聯(lián)隱性遺傳：X染色體IL2受體

鏈基因突變TAP基因突變→MHCI表達(dá)低II類反式活化子、RFX5和RFXAP基因突變→MHCII轉(zhuǎn)錄障礙表現(xiàn)：T、B細(xì)胞分化發(fā)育成熟障礙癥狀：對各種類型感染均易感9免疫缺陷性疾病5%5%50%20%20%常染色體隱性SCIDX-聯(lián)SCIDADA缺陷PNP缺陷其他原因（TCR及IL-2免疫缺陷,MHC表達(dá)缺陷）9免疫缺陷性疾病嚴(yán)重聯(lián)合免疫缺陷病(severecombined-immunodeficiencydisease,SCID)9免疫缺陷性疾病性聯(lián)重癥聯(lián)合免疫缺陷病(X-linkedSCID,XSCID)Mutationsinthe

c(common

chain)chainofthereceptorsforinterleukinsIL-2,-4,-7,-9and-15**Signaltransduction,**lymphocytedifferentiation,proliferationandmaturation9免疫缺陷性疾病9免疫缺陷性疾病IL-2RIL-4RIL-7RIL-9RIL-15R

-鏈參與組成的細(xì)胞因子受體共用的

鏈9免疫缺陷性疾病9免疫缺陷性疾病ADA與PNP基因突變造成免疫缺陷的途徑GMPAMPIMP肌苷腺苷鳥苷ADA6-氧嘌呤PNP鳥嘌呤PNP黃嘌呤尿酸腺苷脫氧腺苷鳥苷脫氧鳥苷dAMPdADPdATPdGMPdGDPdGTP抑制核苷酸還原酶T、B細(xì)胞增殖障礙II嘌呤核苷磷酸化酶（PNP）和腺苷脫氨酶(ADA)缺陷Mutationofthepurinenucleotidephosphorylaseandadenosinedeaminase9免疫缺陷性疾病OKT3抗體,IL-2ADAADAADAmonocyteTcell9免疫缺陷性疾病9免疫缺陷性疾病3、吞噬細(xì)胞缺陷：慢性肉芽腫病(chronicgranulomatousdisease,CGD)染色體水平：性聯(lián)隱性遺傳：X染色體p21編碼細(xì)胞色素b19kD鏈常染色體隱性遺傳：輔酶Ⅱ（NADPH）氧化酶中47kD和67kD缺陷9免疫缺陷性疾病正常吞噬細(xì)胞消化無能吞噬細(xì)胞細(xì)胞色素b558細(xì)菌黃素蛋白吞噬體細(xì)菌吞噬體中性粒細(xì)胞NADPHH+NADPHH+e-

+O2O2-H+H2O2慢性肉芽腫?。–GD）9免疫缺陷性疾病Th1細(xì)胞多核巨大細(xì)胞巨噬細(xì)胞內(nèi)皮樣細(xì)胞細(xì)菌纖維母細(xì)胞慢性肉芽腫9免疫缺陷性疾病9免疫缺陷性疾病Granulomainaleprosypatient9免疫缺陷性疾病(2)白細(xì)胞粘附障礙(leukocyteadhesiondeficiency,LAD)中性粒細(xì)胞的滲出過程

ABC毛細(xì)血管內(nèi)皮細(xì)胞侵入細(xì)菌附壁粘著游出ECEC9免疫缺陷性疾病

整合素(integrin)CD18geneencodeLFA-1Mac-1/CR3gp150,95/CR49免疫缺陷性疾病9免疫缺陷性疾病This3-year-oldgirlhadleukocyteadhesiondeficiencytypeI(LADI)withcompleteabsenceofCD18expression.Thetypicalgingivostomatitis(齦口炎),whichwasculture-negativeforanypathogen9免疫缺陷性疾病This10-month-oldpatientwithsevereleukocyteadhesiondeficiencytypeI(LADI)developedacervicaladenitis（頸淋巴結(jié)炎）causedbyKlebsiellapneumoniae.Followingincisionanddrainage,woundhealingtook4months.9免疫缺陷性疾病pqCGDWASSCIDXLAXLPXLHM9免疫缺陷性疾病9免疫缺陷性疾病9免疫缺陷性疾病4、治療策略骨髓移植、胸腺移植或干細(xì)胞移植（無相同HLA配型）注射抗體注射抗生素免疫調(diào)節(jié)：如：IFN-

改善慢性肉芽腫病人嗜中性粒細(xì)胞的功能9免疫缺陷性疾病9免疫缺陷性疾病感謝上帝給了我一雙好用的手！9免疫缺陷性疾病二、繼發(fā)性免疫缺陷性疾病

繼發(fā)性免疫缺陷病是指非先天性繼發(fā)于某些疾病或使用某些藥物后產(chǎn)生的免疫缺陷病。9免疫缺陷性疾病病因：①感染②營養(yǎng)不良或營養(yǎng)過度③惡性腫瘤：何杰金氏病→T細(xì)胞免疫受損慢性淋巴細(xì)胞白血病→體液免疫減弱。④其它：消化系統(tǒng)疾病、代謝性和內(nèi)分泌性疾病放/

化療、免疫抑制劑9免疫缺陷性疾病獲得性免疫缺陷綜合征（acquiredimmunedeficiencysyndrome，AIDS）——艾滋病

主要靶子是免疫系統(tǒng)

9免疫缺陷性疾病HIVIncubationPeriod(Adults)Not

Infected-Infected---Infectious---AIDS----Death--3-10years---1yr-9免疫缺陷性疾病9免疫缺陷性疾病一、流行情況世界范圍1981年5月——第一例，年底共152人1983年13500人1999年50，000，000人估計(jì)2000年30000000—1億人至1999年底死亡人數(shù)16，000，000人我國1985年第一例1999年15088人估計(jì)實(shí)際40萬2000年50萬2010年將達(dá)1000萬9免疫缺陷性疾病9免疫缺陷性疾病Subsaharan撒哈拉沙漠Inthefiveminutesthatittakesyoutoreadthisorwalkinthehallwaybetweenclasses,25peoplearoundtheworldwilldieofAIDS,thediseasethatdestroysthebody'simmunesystem.HIV,thevirusthatcausesAIDS,hasinfected42millionmen,womenandchildrenworldwide,5millioninthelastyearalone.9免疫缺陷性疾病AIDSCasesbyAgeandSex,Reported1981-1998,UnitedStates

9免疫缺陷性疾病EstimatednumberofAIDSrelateddeathsworldwide1980-2000

WHO9免疫缺陷性疾病MothertochildtransmissionofHIV1979-1999bybreast-feedingorothercause

WHO

9免疫缺陷性疾病9免疫缺陷性疾病9免疫缺陷性疾病9免疫缺陷性疾病二、病原：HIVdsRNA兩條相同的單股正鏈RNA主要靶子免疫細(xì)胞

9免疫缺陷性疾病HIVbuddingfromhumanlymphtissue(TEMx133,335)9免疫缺陷性疾病9免疫缺陷性疾病9免疫缺陷性疾病三、HIV的致病機(jī)制TAT:Trans-ActivatorofTranscriptionREV:RegulatorofVirionproteinexpressionNEF:NegativeRegulatoryFactorVIF:VirionInfectivityFactorVPU:ViralProteinUVPR:ViralProteinR病毒gene9免疫缺陷性疾病ThenecessityforCD4antigenexpressionforentryofHIVintoahumancell.HeLacellsdonothaveCD4antigenandarenotinfected.HeLacellstransfectedwithCD4geneareinfected

9免疫缺陷性疾病NEFeffectsonCD49免疫缺陷性疾病NEFeffectsonCD49免疫缺陷性疾病9免疫缺陷性疾病NEFinducescytokinesthatattractTcellstoaninfectedmacrophage9免疫缺陷性疾病趨化因子受體CXCR:CXC類趨化因子受體CCR:CC類趨化因子受體CC類趨化因子CXC類趨化因子CXCCCH2NCOOHCOOHH2N(基質(zhì)細(xì)胞衍生因子)(趨化因子炎性蛋白因子)9免疫缺陷性疾病9免疫缺陷性疾病Chemokinereceptorsareinvolved,inassociationwithCD4antigen,ininfectionbyHIV(left).Thechemokinecanblockattachmentofthevirustoitsreceptors(middle).MutationsinthechemokinereceptorcanleadtoresistencetoHIVinfection(right)

9免疫缺陷性疾病趨化因子受體拮抗劑抗HIV-1治療9免疫缺陷性疾病Th表達(dá)趨化因子受體的細(xì)胞9免疫缺陷性疾病A.BuddingcausescelllysisSomepossiblemechanismforthelossofT4cellsafterHIVinfection9免疫缺陷性疾病BSyncytiaformation9免疫缺陷性疾病Multinucleatedcell(syncytium)intouchpreparationfromcutsurfaceofenlargedlymphnodefrompatientwithHIV-1infection.Cellfusionproducingalargemultinucleatedcellisaviralcytopathiceffectcharacteristic,butnotdiagnostic,ofinfectionbyHIV-1.9免疫缺陷性疾病C.InfectedcellsaredestroyedbycytotoxicTcells9免疫缺陷性疾病Virustiter,CD4cellnumberandanti-gp120titerduringthecourseofHIVinfection

9免疫缺陷性疾病Virustiter,CD4

andCD8cellnumber

duringthecourseofHIVinfection

9免疫缺陷性疾病AbundanceofHIVinlymphoidtissueinsituhybridizationoflymphnodesectionsfromarepresentativeHIV-infectedpatientinearlystagedisease.AHIVRNAisindicatedbythesilvergrainswhichappearaswhitedots.Anintensehybridizationsignalispredominantlyrestrictedtotheareaofthegerminalcenters.BHighermagnificationofaprotease-digestedsectionshowingtheintensedistributionofsilvergrainsinthelightzoneofagerminalcenter.9免疫缺陷性疾病LesionsonthestomachofapatientwithKaposi'ssarcoma

Figure-Kaposi'sSarcomaKaposi'ssarcoma(skin).SkinshowingAIDS-associatedKaposi'ssarcoma

9免疫缺陷性疾病ScanningelectronmicrographofHIV-1buddingfromculturedlymphocyte.Multipleroundbumpsoncellsurfacerepresentsitesofassemblyandbuddingofvirions9免疫缺陷性疾病9免疫缺陷性疾病FacialsarcoidosisinAIDS

9免疫缺陷性疾病HairyleukoplakiaoftongueOralthrush.OrofacialgranulomatosiswithcobblestonemucosaCandidaandherpessimplexSevereangularcheilitis9免疫缺陷性疾病CryptococcosisoflunginpatientwithAIDS.Methenaminesilverstain.HistopathologyoflungshowsnumerousextracellularyeastsofCryptococcusneoformanswithinanalveolarspace.CystsofPneumocystiscariniiinAIDS.Methenaminesilverstain.Histopathologyoflungshowscharacteristiccystswithcupformsanddot-likecystwallthickenings.9免疫缺陷性疾病HAART:highlyactiveantiretroviraldrugtherapyFactorsaffectingHIVprogression.TherapeuticstrategiesforcontrollingAIDS9免疫缺陷性疾病TOWARDSANANTI-HIVVACCINEGoalsforananti-HIVvaccineprovidesterilizingimmunity(actagainstfreevirusandHIV-infectedcells)2.depressinitialratesofHIVreplication(long