obligateanaerobes-近畿大学医学部

109-A13重症熱性血小板減少症候群SFTS:severefeverwiththrombocytopeniasyndromeSFTSウイルス：Bunyaviridae科Phlebovirus属マダニ媒介四類感染症MarchtoJuly2021,Emerginginfectiousdiseaseidentifiedastheseverefeverwiththrombocytopeniasyndrome(SFTS)inruralcentralChina.Causewasunknown.Majorclinicalsymptomsincludedfever,thrombocytopenia,gastrointestinalsymptoms,andleukocytopenia;highinitialcasefatalityrateof30%Multi-organfailuredevelopedRAPIDLY—elevatedserumalanineaminotransferase,aspartateaminotransferase,creatinekinase,lactatedehyrogenase;proteinuria,hematuria.FromDr.O’CallaghanVirologyJournalClubApril29,2021Genus

HumandiseaseOrthobunyavirusLaCrosseencephalitis,Californiaencephalitis

Phlebovirus RiftValleyfever(RVF)Nairovirus Crimean-Congohemorrhagicfever(CCHF)Hantavirus Hemorrhagicfeverwithrenalsyndrome(HFRS)

Hantaviruspulmonarysyndrome(HPS)Tospovirus Plantvirus,noknownhumandisease5generaFamilyBunyaviridaeEncephalitisHemorrhagicFeverPneumoniaBUNYAVIRIDAE;BunyamwerainUgandaVirion:ENV,120nm;3Helicalcapsids;three1XRNAs5Genera.2generahaveambisenseRNAs;Phelbovirus&TospovirusTospovirusgenus=tomatospottedwiltvirusM&SRNAsareambisense.NSm34Kprotein=movement.Formstubulesthatpenetratethruplasmadesmatasocapsidscanenterneighboringcell.NSs52Kproteinbinds2XRNAthatcangeneratesiRNAs.TransmittedbyTHIRPSInfectstomato,peanuts,watermelon,zucchini,impatiensS+MRNAs=ambiCaliforniaSinNombreCCHFRiftValleyDr.O’CallaghanJournalClub4/20/12Hantavirus(HFRScontactwithrodents)Nairovirus(CCHF-tick)Orthobunyavirus(LACmosquito)Phlebovirus(RiftValleyFever;mosquito)Tospovirus(Tomatospottedwilt;thrips)PHLEBOVIRUS:68serotypes.

TwoGroups:

1.PhlebotomusFeverGroup55(sandflies)2.UukuniemiGroup13(ticks)

EightmemberslinkedtodiseasehumansAlenquer Chaniru ChagresNaples PuntaToro RiftValleyFever Sicilian ToscanaSFTSVirusisnewGROUPofPHLBOVIRUSGenus.9thPhlebovirustocausediseaseinhumansFromDr.O’CallaghanVirologyJournalClubApril29,2021thripsTheseleavesshowsymptomsoftomatospottedleafvirus./KathieRowell/TheTimesMay12,2021109-A38血球貪食症候群Hemophagocyticsyndrome〔HPS)血球貪食性リンパ組織球症Hemophagocyticlymphohistiocytosis(HLH)EBV関連血球貪食症候群EBV-associatedhemophacotyticsyndromeEBVに感染したT細胞が増殖し、大量のサイトカインを分泌、これによって活性化したマクロファージがサイトカインの分泌や血球を貪食して起こす標準微生物学第12版ｐ423Familialhemophagocyticlymphohistiocytosis(FHLorFHLH)iscausedbyaninheriteddeficiencyofperforinHemophagocytosis:ingestionofredbloodcellsbymacrophages

Pfp-/-miceinfectedwithsometypesofvirusesresultinadiseasesimilartoFHLbecausetheimmunesystemisuncontrolleddemonstratesthatperforinplaysanimportantroleinregulatingtheimmuneresponseHemophagocyticlymphohistiocytosis(HLH)=Hemophagocyticsyndrome(HPS)=MacrophageactivationsyndromeSomedeficienciescanleadtolymphoproliferativediseases(Table4.2)InFHL,mutationspreventNKcellsandcytotoxicTcellsfromreleasingtheircytoplasmicgranules,whichleadstouncontrolledproliferationoflymphocytesandmacrophagesThesecellsphagocytosebloodcellsandreleasehugeamountsofproinflammatorycytokinesCytokineburstexplainstheinflammation,feverandsystemicillnessTcellandmacrophageinfiltrationinliver,spleen,lymphnodes,bonemarrow,andcentralnervoussystemTcellsandmacrophagesrespondstronglytomicrobestocompensatefortheCTLandNKcelldefects?AnemiaThrombocytopeniaHemophagocytosisinbonemarrow,spleen,lymphnodeIncreasedcytokinerelease:interferon-γ,TNF,IL-6,IL-10,macrophagecolony-stimulatingfactor(M-CSF)Treatment:controlthecytokineburstbychemotherapyandimmunotherapywithetoposide,corticosteroidsandcyclosporine,followedbybonemarrowtransplantationHemophagocyticlymphohistiocytosis(HLH)Hemophagocyticsyndrome(HPS)Familialhemophagocyticlymphohistiocytosis(FHLorFHLH)(Table4.2) FHL1:unidentifiedgeneonchromosome9 FHL2:perforin(PRF1)mutation FHL3:Munc13-4(UNC13D)mutation FHL4:syntaxin11(STX11)mutation FHL5:syntaxinbindingprotein(STXBP)2(Munc18-2)mutation Allfourproteinsareinvolvedinthegranule-mediated cytotoxicpathwayoflymphocytesImmunedeficiencysyndromes(Table4.1) Chediak-Higashisyndrome1:LYST(=CHS1)mutation Griscellisyndrome2:RAB27Amutation LYSTandRAB27A:roleinvesicletraffickinginCTL

X-linkedlymphoproliferativesyndrome:SH2D1Amutation NKcellinhibitionleadstosevereEBvirusinfection andsustainedproliferationofCTL(Table4.3a)

Genetichemophagocyticlymphohistiocytosis=primaryhemophagocyticsyndromeAdefectinLYST(=CHS1),whichisinvolvedinintracelluarvesicleformationandtraffickingReportedbyMoisesChediak(1954)andOtotakaHigashi(1956)AfailureoflysosomesandphagosomestofuseproperlyPhagocyteshaveenlargedgranulesandimpairedintracellularkillingabilityPartialalbinism,abnormalplateletfunction,severeimmunodeficiencyChediak-HigashisyndromeOtotakaHigashi,東音高://nurs.or.jp/~academy/igaku/t1/t1241.htm109-A60含み声muffledvoice,

hotpotatovoiceくぐもったような、手で口を押さえてしゃべったときのような声のどの奥からうるんだようなような声がれが出ること

急性喉頭蓋炎、扁桃周囲膿瘍など109-B16原発性免疫不全症慢性肉芽腫症Chronicgranulomatousdisease(CGD)

PrimaryImmunodeficiencyExpertCommitteeMSMD:Mendeliansusceptibilitytomycobacterialdisease5.CongenitaldefectsofphagocytesImmunodeficienciesofphagocyticcellsMyeloiddeficienciesprimarilyaffecttheinnateimmunesystem Phagocyteimmunodeficienciescanbegroupedinto4types:DeficiencyinPhagocyteproduction:Development–defectingenerequiredformyeloidprogenitorcelldifferentiationPhagocyteadhesionPhagocyteactivation:PhagocytosisKillingDefectsinphagocyticcellsareassociatedwithpersistenceofbacterialinfection5.3:Defectsofrespiratoryburst6.2,6.3:IRAK4,MyD88deficiency5.2:Defectsofmotility5.1:DefectsofneutrophildifferentiationTable4.1:ImmunodeficiencywithhypopigmentationThemostsignificantproblemistheinabilityofcellstoattachtothevascularendotheliumandmigratetositesofinflammationLADtype1(LAD-1):deficientexpressionofβ2integrinsduetoCD18genemutationsLADtype2(LAD-2):absenceofsialylLewisX:ligandonneutrophilsrequiredforbindingtoE-selectinandP-selectinonendothelium Causedbyfucosetransportergenemutation:thefailuretotransportfucose intotheGolgicomplexresultsinfailuretosynthesizesialylLewisXLADtype3,deficiencyofKindlin-3,requiredforfirmadhesionLeukocyteadhesiondeficiency(LAD)(Table5.2)Leukocyteadhesiondeficiency(LAD)resultsfrommutationintheCD18molecule–theb2chainoftheintegrinfamilyTheresultisalossofsurfaceexpressionofkeyintegrinmolecules:Abnormalfunctions:endotheliumadherence,neutrophilchemotaxis,phagocytosis,cytotoxicityLADtype1Mac-1p150:95109-D4解答：d.落葉状天疱瘡選択肢：e.疱疹状皮膚炎dermatitisherpetiformisヘルペスウイルスとは無関係グルテン過敏腸症Celiacdisease(Celiacsprue

glutensensitiveenteropathy)Chronicsmallintestinalimmune-mediatedenteropathyprecipitatedtodietaryglutenAcommoncauseofmalabsorptioninCaucasiansIntheUS,estimatedincidence:1:113Onset;fromthefirstyearthroughtheeightdecadeDiarrhea,steatorrhea,weightloss,consequenceofnutrientdepletion(anemiaandmetabolicbonedisease)Gliadin,acomponentofgluten(wheat,barley,rye)Serumantibodies:antigliadinIgA,anti-transglutaminaseIgAHLA-DQ2allelepresentin80-95%ofpatients;HLA-DQ8Associatedwithdermatitisherpetiformis(IgAdepositionintheskin),diabetesmellitustypeI,thyroiditis,IgAdeficiencyEnteropathy-associatedT-celllymphomaAftergluten-freedietDermatitisherpetiformisSkinIgAdepositionAmultisystemdiseaseresultingfromanautoimmunereactiontoinfectionwithgroupAstreptococciAlmostallofthemanifestationsinmanypartsofthebodyresolvecompletelyExceptioniscardiacvalvulardamage:rheumaticheartdisease(RHD)Diseaseofpoverty:lesscrowdedhousingandbetterhygieneresultedinreducedtransmissionofgroupAstreptococci+antibioticsandimprovedmedicalcare109-D14急性リウマチ熱Acuterheumaticfever(ARF)Harrison’sOnlineMolecularmimicryinrheumaticfeverRHD:rheumaticheartdiseaseStreptococcalMproteinareimmunologicallysimilartomyosin,tropomyosin,keratin,actin,laminin,vimentin,andN-acetylflucosamineAntibodiesthatrecognizecardiacmyosininthemyocardiumalsorecognizethevalveendotheliumandlamininOncediseasehasbecomechronicinthevalve,otherproteinsinthevalvesuchaslaminin,vimentin,collagenandothersmaybepresentedtotheimmunesystemandepitopespreadingwouldbepredictedtooccur12-4Epitope(determinant)spreadingInanimals,autoimmunediseasecanbegeneratedbyimmunizingautoantigen(proteinX)inadjuvantFirstresponseisdominatedbyTcellresponsetoonepeptidederivedfromproteinXLater,tissuedamagereleaseproteinXandotherselfproteins(proteinY)FurtheractivateTcellresponsestoproteinsXandYExample:12-7Experimentalallergicencephalomyelitis(EAE),animalmodelformultiplesclerosisSelf-antigenisreleasedfromdamagedtissuecanbetakenupbyantigenpresentingcells(APCs),processedandpresentedtoautoreactiveTcellsFurthertissuedestructionbyactivatedTcellscausesthereleaseofmoreself-antigenfromtissuesTheresponsecanthenspreadtoinvolveTcells(orantibodies)specificforotherself-antigensinaprocessknownasepitopespreadingEpitopespreading109-D44Mumps急性耳下腺炎MumpsChildwithparotitis(CDCwebsite:)Mumpscausessalivaryglandswelling,particularlytheparotidglandMumps;“Otafuku〞inJapaneseOtafuku,Japanesemask(“fuku〞=swelling)109-D49項部硬直髄膜炎ViralMeningitisvs.EncephalitisViralMeningitis(Enteroviruses,HIV,HSVtype2,Arboviruses)

HeadacheStiffneckPhotophobiaLittlealterationinconsciousnessNofocalsignsViralEncephalitis(HSV,Arboviruses,Rabies,Nipahvirus)AlteredconsciousnessFocalneurologicalsignsSeizuresMeningealsignsDr.JohnE.Greenlee,MD,UniversityofUtah109-E50慢性炎症性脱髄性多発根神経炎109-E52クループParamyxoviridaeHumanDiseasesFamilyincludesnumeroushumandisease-causingmembers:PaRaMyxovirus:Parainfluenza,Respiratorysyncytialvirus,Rubeola(Measles),MumpsSubfamilyParamyxovirinaeMorbillivirus(measles)–fever,cough,conjunctivitisleadingtomacropapularrash;canbefatal;Subacutesclerosingpanencephalitis(SSPE)Rubulavirus(mumps)–feverleadingtosalivary(parotid)glandswelling;canbetesticularandcentralnervoussystem(CNS)involvement;occasionallyfatalRubulavirus(humanparainfluenzavirus2/4a/4b)–acuterespiratorytractdisease;feverleadingtobronchitisandpossiblypneumoniaRespirovirus(humanparainfluenzavirus1/3)–acuterespiratorytractdisease;feverleadingtobronchitisandpossiblypneumonia;“croup〞ininfants<6mos.Croup109-E52急性喉頭蓋炎：選択肢正常2021年近畿大学６年寺田徹さんクリクラ109-F13選択肢：手足口病Hand,footandmouthdisease(HFMD)Vesicularlesionsonthehands,feet,mouth,andtongueOccursinchildrenCausedbyenteroviruses,includingcoxsackievirusA16,10,andenterovirus71Mildlyfebrile,andtheillnesssubsidesinafewdaysCoxsackievirusThefirststrainswereisolatedfromtwoparalyzedboysinthevillageofCoxsackie,NewYorkMeningitisandencephalitisMyocarditisAphtho:fromGreekaphtha,"vesiclesinthemouth";English:aphtho,"thrush〞Entero:fromGreekenteron,"intestine〞Hepato:fromGreekhepatos,"liver“Kobu:fromJapaneseKobu"humporknob“Rhino:fromGreekrhis,rhinos,"nose"

ThetwooriginalhumanrhinovirusspecieshavebeenmovedtothegenusEnterovirus;thegenusRhinovirusnolongerexists.Whittonetal.,NatureReviewsMicrobiology2005v.3p.765GenusAphthovirus

Typespecies:Foot-and-mouthdiseasevirus(FMDV)Infectcloven-hoofedanimals(cattle,goats,pigs,sheep)Rarelyinfecthumans7serotypes,eachwithsubtypesLoseinfectivityatlowpHvaluesoflessthan6.8The“typespecies〞:thevirusinitiallynecessitatedthecreationofthegenusandbestdefinesoridentifiesthegenus

PicornaviruspathogenesisThetargettissueinfectedbythevirusdeterminesthepredominantdiseasecausedbythevirus.Coxsackie;coxsackievirusecho;echovirus;HAV;hepatitisAviruspolio;poliovirusrhino;rhinovirus.109-I67SSPE亜急性硬化性全脳炎ADEM,acutedisseminatedencephalomyelitisMIBE;measlesinclusionbodyencephalitisADEM,demyelination;MIBE;inclusionbodyandviralantigenSubacuteChronicAcuteSSPE,subacutesclerosingpanencephalitisOccursyearsordecadesafteraninitialmeaslesinfection0.4to9.7permillionpatientswithmeaslesMutationsintheMproteinClonalexpansionofthemutatedviruswithinthebrainMproteinisnotproduced,nobuddingCellfusionbytheFandHproteinsismaintained,allowingthevirustospreadwithinthebrainbylocalcellfusion;virusevadestheimmunesystem,anti-virusantibodiesotherthanMproteinBrainatrophy,gliosisandmononuclearcellinfiltration,andrarefiedandglioticwhitemattergliosis

[´´+osis,condition]:proliferationofastrocytes=scarintheCNS.ArarediseaseintheUS,withfewerthan10casesperyear,sincetheintroductionofmeaslesvaccine(0.4to9.7permillionpatientswithmeasles)Mostpatientshadtheirmeaslesinfectionpriortotheageof2yearstheonsetofdiseaseoccursbetweentheagesof5to15yearsin85%ofpatientsThediseaseusuallybeginswithpoorschoolperformance,personalitychangesandthendementia(stageI).Myoclonus,seizures