As yl,saaw ’ist oltasm etterb to geonir het esurpict ehnw seilbo.ps hisT naeetmnlg ash a epiptc luce,r hhiwc ew wokn is aecsud eprmndloateiy by H. yriopl ineot.incf .H iplyor pcurosde esopreast nda rrlaiacypult ,esraeu hicwh lawlo ti to eneicsra eth pH fo tis lclao rovnnetnmie by cvgenila urae iont m,naioam ihchw si cixto ot racsigt uacos.m Teh utiperc aemontesdtsr H rilyop, hicwh rea tdvniee ithw sirlve n.isntaig

anseIc oaenyn eesl swa nnikihtg eth :emas
I aws custk ewbeetn isht and rtavani fo onunknw e.iafciniscng Hewero,v airavtn fo nwnnkuo iiiecfcanngs si a usenceqe ont a lnsgie etnoiduelc

aFer = aglymdaa

Tath si lal I tenadw ot yas utb I usseg ttha si too rhots to eb tdaepcec by the wr.ombef

yhTe eahv sbiddrece hwta oyu uamses is a lcicass eacs fo o.uipnanem tBu, APN ni’st na awsnre ohecci. Whta teh xent bste t?gnih The e!ucsa lOd afilr eopple and( a)ohlciscol oelv to gte ioapisntra pomnui.nae RLL si hte sotm noomcm tse,i wichh tyhe eahv rpivodde a(tnkh u,oy gbi ctlivera n.rhc)bsuo Thye neev gaev you teh ihtn htat teh pneatti sah “ycufifldti ”gliosla,wwn hwhci is dceo orf “ieapstsra ehwn wsogiwl.”lna

oD’nt elt meht bdnil ouy wtih shit it’entaps rei.smy heT sseui of the yda si ahtt eh hsa a VDT. a’hTts hwy he mcae ot hte ER ni het tfirs ncseneet dan thwa hte uoatudlnsr swohs at the n.ed etisnPat ihtw anrecc ear begaluepharoycl.

lgreaiF X is a GCG ercoteuniltdi erptae esoapinxn sodrierd hi(whc leik ’nntiHngsuot is a stte av)ifro.te heT trmleana clenu si teh htni ot het k-Xndeli n.irnchetaei mAktuils-ie vshrebiao nda vretliaeyl elrag head aer onmmco; garel ttsieelcs yoln papaer artef ep.urbyt

A new gitlriesnb sedesia ni na dleor sreonp si ylclapyit oigng ot be a ehpumigps tqoenus.i ehnT oyu ujts haev ot rbrmeeem hte feeceirdfn eewtnbe lsuublo pmiehogipd vs ihmppsueg iusga.rlv uslBluo pigmeihdpo is itzhedraaecrc yb het olss fo misdmsshomeeeo that ibdn oektnercsiyta to eth anstembe r,mmeeban gtseruiln ni aullb gbi( )ribsstel in aarse fo icitforn ocei(hC .)A tPiesant whti pgmeuphis vsaigurl loes ihret eemdossmso hiw(ch nibd soikyntartcee to ceah re,toh) os atth ihter ksni si urpes reba,fli hhcwi slrtsue in urltioenac. huMto rseulc rea mroe mnocom in PV.

pabieazeCmarn si a noiouostr Y504CP ed,irunc os ouy duoslh eb senugigs litamemsob no eatmrt .hatw 50PC4Y slpay an nmtiaorpt oelr in tohb ivimnat D aatoviioncbti and dtgaeondira in het rvei.l

oYu nac kool at isht oqiusnte itats.cyglarel

1. nrtSheou blot &-t-g; so .DNA
2. ehyt are usign an caeoeudlensn ot trrasnfe s,ibt siht 'edtosn lalrye enma iaynhtgn to oyu .yte
3. cAND is rnbigop fro glseni aitonlntluubm-csgnoniom r.enogi

hsa'Tt pnrmtioat, asbeeuc nwo yuo nokw yteh rea lkgoino at teh nsntcoat rgeoni fo mogmunbilnulio aak Fc fo teh eyahv cn.iah

So yhw si iths ADcN ahtt nodcees cF, gthgniil up nlyo oecn in ertho ssesitu, but eth easm NDAc htsgli up elmutilp siemt ni anle 2 bon(e mra)?owr hisT is ,besuace ta eht oenb wromra anordm onioemtbiarcn of hgtli or yvhae inhac ocrc,su nda uor ANcD si tsepren ni deerftnif maonrd csbnmniotoai htwi thigl niac.hs ahTt cicpeisf cAND eeuesncq yteh sdeu dnti'd neaghc bweneet eht usessti ro enev wtihni teh neob rwamr,o nad ti llwi oyln nibd ot eth one neeg nqeeuc.es eTh caft st'i ilhngigt up etillmup items lltse uoy htta eth asem cuqensee si ,epentsr oury qsitenuo is hyw os amny iems.t

lAos a iesd tnoe, netroshu sbotl rea item u,onmignsc so labs use trhoe oshtmde ot od het mase tihng ikel( ,)CRP tbu eounhtsr osblt aer tilsl teh etbs ehwn it mecos ot incecghk ullmmbiuognoin nad T llce tercpero eneg emrerarganetn.

reaxnoiA edsal to noogopodarhtipcy osgymain,dhop as het dbyo irzeseal atth eht isployisbit of inignhsuro a stefu is roez adn gevsi pu hte .eerspnet ese’Trh a tol of unrpioptsg atda, ubt oen hsulod segsu shit asnerw cone ouy erda het odrw ”ystngm“a r(o en.”cdr)a“

Tsih whloe qsnueoit si on teh ftreindfe ytesp fo .hsviieyypiersttn (g.p 113 0A)291F

piohnleiso tnraioualndeg → ypTe 1 treiyyesvhsntpii t(asm sclle ya,ler eonol/ithsopehriss )elrat

radpesdiew pstasiopo fo B clsoemhtpyy → B ymotchelysp aer dnevoilv in Tpye 2 v.stytinpireehiys eaesdWdirp sptpaioos ulwod ton co.ruc If ng,htniay B ellcs lwodu otirp?faeler

ikeotnCy teoisnecr by nrlauta klelri lsecl → NK lecsl sue opfrneri adn ygaerznms ot edcnui soisptpao in ytpe 2 iytvepthseriins.y (otN resu if eyht ecrstee yan etnvealr oy)et.s.ickn.

memniu mlxcoep dpioeinots in ssueist → mesur eiksssnc epyT( 3 itnvspetsiihre)yy

capolnoyll ecT-mlphtyoy otinivacat → teyp 4 hisvpityesintyre

Whne oelppe go pnma,gic ouy shuldo eb khiigntn of tcionozo etsi.coifnn unF ftc,a ewN xcMeio elasd teh rucnyto ni assec of elagup. s,Ye taht eal:upg eairnisY t.pisse eTh cbnoi“”ub rtap fo nbibocu aulpge ersfer ot eht nwlosle tinfeced esdno u)bb“s(eo” cithiactcasrer of teh a,essied hiwhc notef elivovn the niorg ub(bo si teh Geekr wdro ofr ogr,ni how ?)knwe. In hsit c,eas rheet’y losa riienscdgb a tocicnre aprrieetolhc no.ed ssicalC ttaetenmr si whti osgiesionm,cdlay whcih dbni to teh 03s imoolbsra t.nsuuib oe(Nt taht ,maeuarTil cesdua yb aehtnro ag-amgeervnit iraabtce naeFilclasr tsersnuila acn sneetrp milrsalyi utb si oemr ocmnmo ni teh siwmdet. ,seedrlRgas hte wto rae ntfoe ulmepd tehgeotr, eth icaoaibtlnmir ateetrmtn si ralis,im and teh waesrn ni iths esca owldu be hte .amse)

ree(F 1,20 9120 atdUpe)

oT sothe odwgirnen ahtw eraalovl orpinstisoe ,is it si a earr nlug rddeoisr raareczdhitce by alomanbr camialnutcuo of setitn-arrdcdfveau sooplirptnie twhini het .ivelaol eseoSmimt it acn curco ceyosadrn to lgnu ncisiefo,tn huogathl allsyuu it si na nitamumeou possce.r

arlO eleiscv i(thn )n.thi tgBelniirs ulsavceir elsion on teh hdna. oN veef,r tno paxinrgoc.ie-pta Tihs si serpeH (uoy amy rbrmeeem stensdti gnegtit rpecetih tlwhoiw ni yruo d,tueiss chhiw is hwat tsih .is) Msto lfkos tge 1VSH sa ,eldcnihr ohhutg uvolyobsi ont lal rae am.ipcostymt SHV si a garle nees,drtoudabld- airlne DNA rsi.vu

idlsimcAyengoso hW(hic ithbisin )30S aer udcelpo wthi ecll lalw tciave sangte - e..g celii,iPnsnl yVcnmonica

tehc(ySk eeeefncrR on conAgsymldeioi cheSk:t et-acatalmB b)b!m!o

opmrAeatipx tsagfni hgoopysily iimg:nt het etss-opoaprbtvi haesp (246- hrsuo erfat a aeml) is nioadtmde yb nyssollgcieo.yg ulensosniceeGog romf 42 ouhrs to 2 das.y enhT ioestks.

nvo ediWrbnall esiasde si by raf teh somt mnoocm iiendethr ndlbiege hdit.sasie ,Fytlnuqere the yoln tbaloryaor yramoailbtn is reiesdacn nlbdieeg emit yrtallei(l you cpkri hte netatip adn see hwo gnol it akste mhte to tpso .gbledine) nO t,eSp ndglbeie wmnoe aehv .DVW iegBdlen bsoy vhea .hoimaeihpl

eH ash melabyr(spu VR)S tor.hicbionsli VRS si na NAR viusr thta netesr the ecll iva a suofin petroni wh(hci is hte eatrtg fo eht cyhpirlpaotc lmaconnolo ndiabtoy udgr umbvaPii)lza.

stuJ to dad to aoxaeninlt.p rwnesA si ton icgonanetl draeanl preshaliyap, auseebc tp ahs onalmr staber neltmepovde and onlamr nelatrxe latnigaei. smto onmcmo ptye h-aryxeod2ysl1 dfe uodwl ehav iuesccorpo pyutbre or oairlctl lren.tneaemg ntQiseous syas etpnati ahs noamlr nrpiagpae laneerxt iel.naitag xal7oedys1ayh-r edf wdulo lade ot iuuaosmgb teaanglii in XY dna ni XX heter wodul be no raecysdon xelsua dvpleetomen eabuesc kcla fo sxe o.idssetr uBt niaa,g tioqnuse ssya pt ash rlaomn esabtr eloepnmdtev and rtnaxlee egalii.nat nI ehxldsyao1r1yB- fe,d XX udwol haev oiitlrn,iiavz ianag ont pcalbaiple hr.ee

dtcorelema lpadiassy wduol evah roem hcsrrittcceasia kile laonrabm e,htet rohte blaonarm nidginsf fmro otrmeecald eayr.l

a pcysh isderrod cuold hrotw uyo of,f ayemb apnttei is nto angeit gnohue dan is not nahgiv a ipreo.d But hety dasi rmnlao meeafl byod taus,hib os I ktnhi thta sesem less lkylei oaedpmrc ot rnaogdne .inivntyisiest

xeS osoocehrmm coimsiams mdae me hktin of nTreru rnmdSo.ey rheeT si a ienuqu ybod iuhabst for uenrrT ndeySrom os asmke hsti a nwogr aenws.r

No teiroaln tewbeen the rmtuai )P( vewsa adn eth QSR emxcopl nesma erh-igtrdede AV kcolb a(ka clto“e”mpe heart ckl.)bo amSmpyictto neve( aa)flt daycdarabri anc rltuse. ”nCa“onn aailtr easwv are nnoipterm ajruulg vsenou soitnaupls thta uccor newh eth raati dan nilecretv crctnoat euolmyatiunlss ih(w,ch fo ceso,ur nstd’eo nmllyora na)phe.p

CNS aiseaisobm si msot suoiltrnooy sdeauc by rgeaaieNl ,eriwofl hcwhi I ecraougen uyo ot eeimmroz sa eth “gtrie-nnibaa aa.mo”be nduFo in swe-fhtarer eoibsd of weart iekl nodps and ak,les it ash trhee fsrom: a sc,ty a rtztooepoih a)bd,oim(e dan a afegiaelbltl .e(.i sah wot aflae.l)lg fnceontIi si iav ftrcoyalo clel osnax rhoutgh teh moirfbcrir elatp ot het rbn.ai

troSke teahzairccedr by eftl srhesmaeiip nda tirhg 21CN ply.sa Csordse ifginsdn nmae a inretsmab onesl.i hgRti ptra(elsia)li tugne,o lefisd-ted toralatcerlan)( eswkneas aesmn eth gnitixe rgith lolohgyapss never sah eenb etfeacdf h(tniwi teh githr amel).ldu C is the idyrapm weerh het tcarpiooilcsn tarct snru to tonrocl cssmlue rrp(oi to hte ud.sta)nioces hTsi si oknwn sa hte lediam emyaudllr sdmenory or enereijD .sednrmoy

yLedgi sclle akem esttsre.tooen yeLgid cell smtoru rne’ta aylswa yllcpoahsiigo ,taeivc ubt tshoe htat rae acn eucas z.snulmiotaciina sluroaGna clle rsmtuo, on hte toehr dhan, eiomstems oucerdp sgteneor wc(ihh anc edla to ococpeirus ertuybp ni ouygn gsirl but thiowseer amy eb ol.ctc)u ataoTsrem rea dsaoblld ttha ytllycpai veah f,ta arh,i e,htte et.c ahomcTse lilw ont be on uyro e.tts nraOiav rcociiadn is ghylih nikeully ot whso up on oruy test, ubt if ti ,ddi it douwl ilekyl erpetns iwht a scslcai icaicodnr donsr.mey

heT aorrw si intoingp to a lrhipunote (ulioebmdlt suuclen:) aimn trefigh of hte enimum tsmesy ni etuca notiflmaiman dna lbratcaei tfeoicinn h(cus as pionaartsi .aenpmuin)o C5a is a ectoiahmtcc trafco fro sPN.M

ilawgSnowl iimtocna dilfu si a ictclria pcnmnoote of nglu vmpldeent.eo ueFsest ihwt sreeve siyohdinoarmolg aer geudpal by yuolarnpm lp,aasoypih hwhci is the ucsea of tdaeh in eefstus rbon thwi trtoPe ymdeorsn (rnale s)eea.gsni

drgAneno estsitiniyinv si usceda yb a edfcveite nengarod pr.oertce THD si eorspeiblns orf tnaeigrc elma enlagiati gidurn elatf xaseul ve.lpeemtndo eTh ufedtal hmuna gernde si le.mfae So a elalycginte mlea ttianep tiwh olecepmt gornedna invitetnissyi si yllaxerent ctlnhlipyeapoy afelm.e aLck of erosenps ot readnla daresonng esenvtrp rhai mioanftor irndgu rypbteu .cer)ear(ahnd

ehT tprieoailrfve sphae of eth aeturmsln yccel is lrcotlnoed yb ltpc-deiycnndnee .seiakns (sihT smaek seens as y-nnidltedececpn neksasi greonv vrtyauill all llleurca diinsiov in cyitakroeu cs).lle

Juts eeubacs she’ vnigah dnortepu(te)c xes soe’dnt name he sd’tnoe heav pselim iefniucsot cslmooseuno.ni heT esx piesilm seh’ alos sknisig nesmooe! hgarsnPytii + lmphy oedns + agutfie = mon.o

Im’ oging to nopit uot ttha a omalrn hyhltae ikd ihwt no iacadrc rtihoys ro spmsoymt dan no ymfila iystohr of udndes airacdc edtha for a eprstp-ros ychsaipl is oabrplyb igngo to ehav a gibenn aexm on ramett wtah ouy htink yuo hrea.

C80D si losa onnwk sa 7.B notQesiu is inkgas if ouy onwk ahtt 28CD ec)llT-(s esctarnit htiw B7 (PC)A sa a ariltmsooctu-y lgsani ot vticatea het le-cT.l

Looks leik the ptureci is sanoedtgrntim aoctnct rdeiiamtts edu( ot hre etnrce esu of ewn ihra )dye cwihh is a tepy IV HSR

I yaluslu rbeemrme htta B7- is no hte Bll-ce na( PA)C

theOr se:anwrs

oessbauce lngda → en,ca tiericmabuuCt nscea rmyelrfo( Piibontucriepoamr asc)ne

roepiacn gdaln (kaa eswta lgnd)a → eTh nesbsatcu trcsedee is erhctik ntha incecre stewa nda idpesovr riuetsntn rfo tabeaicr no hte nik:s the citesraa'b etinomdiposco fo eswat si wtah acrsete eht iracd d.oor

nericec adngl → edsu to eeecrts ufstf isidne eht yodb (ei yiavlsra g,alsnd tainccrepa dgn)sal

mrdesi → demldi lyear of .ksin

shTi sntouieq si siagkn otuab VDJ ernrtemgenraa hciwh hapsenp in eth oben marwr.o Teh gnsee are lal hpeocpd pu easubec het B llce si rtgyin ot neetraeg a iqunue inotoimbacn for ist prroeect
ism epl psct.o.n.ce odd dwirngo

ahrptCe 3 of w"ho eht mnemui mytsse wr"oks - osewmea koob

'evI bene gatuth hatt nay vreeosdo etegvnti tiwh a eintpta iuglssatna eth crodot is a ddea gnrrie for PPC eud to ethir ne.ssgrgioa

dhleEontail htitg ’innsctjuo perbmaeitliy is rnidaesec ni oepsners ot uryjin and nioai,latmnfm ilongwla igtnaromi fo hewti bodlo clsle dan dfeinsr ot het iets fo ruinjy.

ieEmcdn ruBtkit hplmmyao acn nhpepa in Brzali as wlle as racAfi w(aj nil,oes pffyu c.a)fe Teh hiarohmogortpcp is gominanetdtsr ngtiebli yodb hsecamgaorp, a tyep fo mchaepgrao nangoiitcn namy te,zpigyohdca ttpcoaipo secll ni iaousvr stseat of erngtdia.oda

itlnptSgi is an itaumemr efsedne sncemamih tofen lpeydmoe by isatnept wtih obrdneleir epnralotysi ioerd.srd nehW gtslnti,pi a pnsreo lisfa to ese rtsohe as aepblca of nahvig boht soipvite dan vetegian ;atuselqii at yna vgnei te,im its’ lal ro hnongti.

ehT ’ttipasne irchcon inayrlammoft mipinsenotu si niilkgl ffo shi ugln heayanpmrc ocsdoe(pm mapyirril of ytep I oseupmc.nte)y pyTe II eynups,comet in dioitadn to mignka ftratun,csa can telecapir ni erdro ot raeclep peyt I csep,youetnm os tehy illw eb drcna.isee ihoCncr nsrtilttaiei mnlimnotafia usestlr ni issrbof,i cheen na sieraenc in lrsatbisf.ob

ixumbiRta C(atDni- 2)0 is nrryeltcu negnriugdo alirst rfo .AS My rpseas nogliogg tusj onw sswoh atth bamtuixri arlybpob lyno hsa a troadmee ecff,te os lpbabryo dsncen-elio to Nt-FniaTa eytarh.p olPb.bary

efaS to asy for odsrab atht :AS aNFT tg&; D2C0

mroF maothaP h.C 2 g.p :41 POM cednciyefi eutsrsl ni eeicvfedt nsocenroiv of 2H2O to lCOH. nrasdecIe sikr orf daaiCnd nfxnis ou(ahhtlg stmo inpastet p)iymcma.tasto Nleuribto uitaortzeml estt is roamnl acseube eht rrytarepsoi rtbus si tclaulay tlsli tn.icta siTh etnitap sah iadnacd tefinocin adn deedla,y tub ltlis cna klli sahpt a, wcihh eenlsymig sgeo gnalo thiw het tafc thta hte atrorryepis trbsu si istll a,ntict but iwuhtto MOP ti yam be edhdnier a et.tlil

This rowm si crasA.si mroF an tiseouncfi eseidsa rctodo:

"hTe eulc is hte e-zsi fi yuo acn ees ti move dna it oskol ekli na rehat o,rmw ’tis irsc!assa In ri,dt skid tge ti morf inclkgi eriht ytrid e!nsrgif eTh dalut okols ikle na wteomrhra nad ti ecsusa the pstmmsyo ddbcsreei tihw eth twsor ecssa agciusn lebow iuorbsc"ont.t

ihTs stoeqniu si iaknd w.ahkc ghRti wa,ya I lcdou eltl tshi swa dee-cnidrescuexi asl,pcoel hhcwi shppean prtety oenft ot err.nuns I ikcped timcnoauo fnsudnctyio aseecbu I didtn' zlariee ttha siht si rsidconede na tottcosh"ari noshny.oe"itp Arfte a logn ,reca uesrrnn aevh a aeedrcesd SVR mrof lla of het lbood fwol iogng ot .esslmuc cneO tehy s,opt bodlo os,lop tns'oed tge cbka ot the ol eodnlo dna eyht llpas.oce tuB ffs I sllti t'ddin kipc tsiasthroso bcesaue I itknh of lod pepelo. kucF em

ddaeephesgW- eohtnsyypdi ;-g-&t nelar .atfnric seyndiK eecvier a aglre aomtun fo d'byso daaccri ot,utup os ethy are a ocnomm stei fo fcrioatnni deu to oibelm rofm altiAr oini.llfibtra

otH btu ciftulsi,olil i’st a h.itgn iCayslllsac pon.aedsmuos

alotT lhrppeaeir ceieasrstn goes onwd uigdnr esexreci as het sereoralti gplyupnis uscmle nad knis tedial.

Teh toposbracerer rae ttehcsr rpcsereto he(t eorm dulif in the e,sevsl eht emor eyht .ifre) So a etnpiat thwi hcoearrhgmi scohk liwl ees a eesaecrd ni eht prebtrcoeroa iinfgr t.era iocttnivaA of SARA illw slrute ni ncdaeersi svrlacau tsecnreais tosv)nnrio(csitcao ni rdeor ot amtannii obdol ue.serrsp ndA arlslacip,ie hcsu as shoet in hte y,neikd lwil eb rmedip orf enotirospr dna not iaitfrnlot on( eno ntwsa ot pee uot ogdo uleitd ueirn henw ’eteryh ay.rehddtd)e ew,Lekiis mesistcy alisaclerpi liwl rferpe to lodh oont mlpsaa dan ton tel ti kela niot eht iuitrmsntite sr(.ianid-)hptcg

Sueautcb dionbcem aingeertnedo v(iorpsseger eprlepriah eyossnr dan mroto sol)s is a eatl gnis of 1B2 eycdencfi,i chhwi si mnmoco in dlo peelo.p On e,saxm a riarciegt eipatnt how leisv eanlo nad yma avhe a ae“t dna toat”s tdie si ykelil to vahe tavnimi edicsienfe,ic ulcyratrpali of toelaf nda .B21

A mnmiecon I sue:

"hCorto dyust A sutyd in hhicw a iddfnee proug of elopep (teh trohoc) is wdololef erov mie,t ot mxeneia inaactissoos wenbtee infdrefte iseovertnnnit ecrveeid and esesnutqub tsc.omuoe

Ceas ssreei eOssribnoatv rae edam no a eerssi of d,dsuiainvil sulualy all rcgeienvi teh smea ienvt,iretnon oerefb adn trfea na irnvnetoenit utb thwi no locntro p"gro.u

S:rucoe h./p.g//winCcet3l5m1bwn/vlthc/pticirma.P:0s7noM5w9/.s

aeCs crtooln.][." . an tceoomu of nesiertt si itfsr fideend dna tenh ebsujstc aer etlecsed itwh e(ssac) dna hwttuoi tr)oo(scnl teh itdnsadege .toecoum The ttiinavgesor then oslok kbca in mtie ot mocerpa hte wto sorpug rof a sirk ctaofr ro othre uxeoserp or naemttetr of tsneiret. ,eherorTfe eth losroeacn-ct utsyd signed is tireelynnh i.recorteetsvp"

S:roeuc /ti/i2/4r/9//ymc83teo/u.5on4eec:.rup8dchog4tsae7a41ruprmsl1/ac