Types Of Rejection

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Note: Note: Texts exts color colored ed MAROON are from Schwart Schwartz’s z’s (NOT mentioned in ppt). • o TYPES OF REJECTION HOW ORGANS ARE DAMAGED • • • • • • • All All of whic which h are are init initia iate ted d with within in minu minute tes s of rereestablishing the blood sul! to the translant Graft re"ection is a comle# rocess rocess in$ol$ing se$eral comonents o % l!mhoc!tes l!mhoc!tes o & l!mhoc!tes o Macrohages o '!to(ines With Wit h res resulta ultant nt loca locall in)a in)ammato mmator! r! in"u in"ur! r! and gra graft ft damage Re"ection can be classi*ed into four t!es+ based on timing and athogenesis athogenesis,, o H!eracute Accelerated ated acute o Acceler o Acute o 'hronic • • • • • • • • • • • • • • • HYPERACUTE REJECTION  %he most rapid   and aggressi$e form of translant re"ection Medi Mediat ated ed b! rere-e# e#is isti ting ng circ circul ulat atin ing g anti antibo bodi dies es against the graft E#amle, nti-A&O anti antib bodi odies reso sonsi nsible for the the o Anti transf transfusi usion on reac reactio tion n when when atie atients nts rece recei$e i$e an A&O-mismatched A&O-mismatched blood transfusion  %he anti-A&O antibodies antibodies are caable of causing h!eracute re"ection of A&O-mismatched organ translants and the latter ose a ma"or hurdle for the use of animal tissues for translantation suall! occurs within minutes after the translanted organ is reperfused Due to the presence of preformed antibodies in the reciient+ antibodies that are seci*c to the donor antibodies ma! be o %hese antibodies  Direc Directed ted against the donor.s HA anti!ens+ or  Anti"A#O blood grou antibodies o &ind to the $ascular endothelium in the graft and acti$ate the comlement cascade+ leading to  P$ate$et acti%ation  &i'use intra%ascu$ar coa!u$ation o Res esul ults ts in a sw swol olle len+ n+ da dar( r(en ened ed gr graf aft+ t+ wh whic ich h undergoes ischemic necrosis Generall! is not re$ersible+ so re$ention is (e!/ Pre%ention is best done b! ma(ing sure the graft is A&O-com A&Ocomatib atible le and b! er erfor forming ming a r retran etransl slant ant cross-match/ • • • • • • •  %ranscribers  %ranscribers,, Angala 9 A5ul A5ul 9 &alilea 9 :austino :austino 9 ;ere5 ;ere5 012 cr 012 cros osss-ma matc tch h 3 r res esen ence ce of r ref efor orme med d antibodies in the reciient that are seci*c to the donor+ thus a high ris( of h!eracute re"ection if  the translant is erfor erformed med ACCEERATE& ACUTE REJECTION Seen within the (rst fe) da*s osttransl osttranslant ant 4n$ 4n $ol$ l$e es both ce$$u$ar  an and antibod*"mediated in"ur! More common when a reciient has been sensiti+ed b* pr pre%i e%ious ous e,p e,posu osure re to ant anti!e i!ens ns pre presen sentt in t-e don donor or+ re resul sultin ting g in an imm immuno unolog logic ic mem memor! or! resonse/ ACUTE REJECTION .HU/ORA OR CEUAR0 Acute re"ection is the result of the immune s!stem recogni5ing new+ foreign antigens 4n$ol$es both humoral and cellular comonents (rst fe) 4t is mor more li( li(el! el! to ha haen en with within in the the (rst )ee1s after translantations translantations Ma! Ma! stil stilll be trig trigge gere red d at a much much late laterr stag stage+ e+ b! infection or reduction 'haracteristic 'haracteristic features of acute re"ection o %argeted  %argeted or destro!s destro!s graft endothelial endothelial cells o 4n)ammator! in*ltrate of mononuclear leu(oc!tes adher adherenc ence e to $essel $essel endoth endotheli elium um   in*ltrations under the endotheliu endothelium m   edema and searation of endothelial la!ers Most common t!e of re"ection With modern immunosuression+ it is becoming less and less common su sual alll! is se seen en wit ithi hin n da! a!s s to a fe) mon mont-s t-s osttranslant Predominant$* a ce$$"mediated rocess o *mp-oc*tes being the main cells in$ol$ed &ios! of the a6ected organ demonstrates o Ce$$u$ar in($trate o /embrane dama!e o Apoptosis of !raft ce$$s  %he rocess ma! be associated with s!stemic s!mtoms such as o Fe%er o C-i$$s o /a$aise o Art-ra$!ias Howe$er+ Howe$ er+ with cur current rent immu immunosu nosure ressi$ ssi$e e drug drugs+ s+ most acute re"ection eisodes are !enera$$* as*mptomatic suall! manifest with abnorma$ $aborator* %a$ues + e/g/ o Ele$ated creatinine in (idne! translant reciients Ele$ated ated tran transami saminase nase le$e le$els ls in li$e li$err tran transla slant nt o Ele$ reciients Eisodes ma! also be mediated b! a -umora$+ rather than cellular+ immune resonse o # ce$$s ma! generate antidonor antibodies+ which can damage the graft Establishing the diagnosis ma! be di7cult+ as bios! ma! not demonstrate a signi*cant cellular in*ltrate8 secial immunologic stains ma! be necessar!/ CHRONIC REJECTION ;age 2 of 3 • • • • • • • • suall! de$elos slowl! and insidiousl! o$er mont-s and *ears 'haracteri5ed b! a rogressi$e decline in graft function ;rimar! cause o Antigraft immune resonse  Suorted b! the fact that de$eloment of  chronic re"ection is strongl! associated with re$ious eisodes of acute re"ection+ and also with the degree of H