Note: Texts colored MAROON are from Schwartz’s(NOT mentioned in ppt). TYPES OF REJECTION • HOW ORGANS ARE DAMAGED • All of which are initiated within minutes of re- establishing the blood sul! to the translant • Graft re"ection is a comle# rocess in$ol$ing se$eral comonents o % l!mhoc!tes o & l!mhoc!tes o Macrohages o '!to(ines • With resultant local in)ammator! in"ur! and graft damage • Re"ection can be classi*ed into four t!es+ based on timing and athogenesis, o H!eracute o Accelerated acute o Acute o 'hronic HYPERACUTE REJECTION • %he most rapid and aggressi$e form of translant re"ection • Mediated b! re-e#isting circulating antibodies against the graft • E#amle, o Anti-A&O antibodies resonsible for the transfusion reaction when atients recei$e an A&O-mismatched blood transfusion %he anti-A&O antibodies are caable of causing h!eracute re"ection of A&O-mismatched organ translants and the latter ose a ma"or hurdle for the use of animal tissues for translantation • -suall! occurs within minutes after the translanted organ is reperfused • Due to the presence of preformed antibodies in the reciient+ antibodies that are seci*c to the donor o %hese antibodies ma! be Directed against the donor.s HA anti!ens+ or Anti"A#O blood grou antibodies o &ind to the $ascular endothelium in the graft and acti$ate the comlement cascade+ leading to P$ate$et acti%ation &i'use intra%ascu$ar coa!u$ation o Results in a swollen+ dar(ened graft+ which 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-comatible and b! erforming a retranslant cross-match/ o 012 cross-match 3 resence of reformed antibodies in the reciient that are seci*c to the donor+ thus a high ris( of h!eracute re"ection if the translant is erformed ACCEERATE& ACUTE REJECTION • Seen within the (rst fe) da*s osttranslant • 4n$ol$es both ce$$u$ar and antibod*"mediated in"ur! • More common when a reciient has been sensiti+ed b* pre%ious e,posure to anti!ens present in t-e donor+ resulting in an immunologic memor! resonse/ ACUTE REJECTION .HU/ORA OR CEUAR0 • Acute re"ection is the result of the immune s!stem recogni5ing new+ foreign antigens • 4n$ol$es both humoral and cellular comonents • 4t is more li(el! to haen within the (rst fe) )ee1s after translantations • Ma! still be triggered at a much later stage+ b! infection or reduction • 'haracteristic features of acute re"ection o %argeted or destro!s graft endothelial cells o 4n)ammator! in*ltrate of mononuclear leu(oc!tes adherence to $essel endothelium in*ltrations under the endothelium edema and searation of endothelial la!ers • Most common t!e of re"ection • With modern immunosuression+ it is becoming less and less common • -suall! is seen within da!s to a fe) mont-s osttranslant • Predominant$* a ce$$"mediated rocess o *mp-oc*tes being the main cells in$ol$ed • &ios! 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!mtoms such as o Fe%er o C-i$$s o /a$aise o Art-ra$!ias • Howe$er+ with current immunosuressi$e drugs+ most acute re"ection eisodes are !enera$$* as*mptomatic • -suall! manifest with abnorma$ $aborator* %a$ues+ e/g/ o Ele$ated creatinine in (idne! translant reciients o Ele$ated transaminase le$els in li$er translant reciients • Eisodes ma! also be mediated b! a -umora$+ rather than cellular+ immune resonse o # ce$$s ma! generate antidonor antibodies+ which can damage the graft • Establishing the diagnosis ma! be di7cult+ as bios! ma! not demonstrate a signi*cant cellular in*ltrate8 secial immunologic stains ma! be necessar!/ CHRONIC REJECTION %ranscribers, Angala 9 A5ul 9 &alilea 9 :austino 9 ;ere5 ;age 2 of 3 • -suall! de$elos slowl! and insidiousl! o$er mont-s and *ears • 'haracteri5ed b! a rogressi$e decline in graft function • ;rimar! cause o Antigraft immune resonse Suorted b! the fact that de$eloment of chronic re"ection is strongl! associated with re$ious eisodes of acute re"ection+ and also with the degree of H<A mismatch • Ris1 factors 0all of which in$o(e innate immune resonses2 o 4schemia=reerfusion in"ur! o 4mmunosuressi$e drug to#icit! o H!erliidemia o 4nfections • Diagnosis o 'haracteristic features %hic(ened arterial intima due to edema and in*ltration through the organs 'lassic hallmar( of chronic re"ection, - Smoot- musc$e ce$$ pro$iferation in t-e media$ $a*er of %esse$ $umen artial or comlete obliteration of the $essel lumen+ disruted elastic lamina+ or ma! demonstrate roliferation • Now that short-term graft sur$i$al rates ha$e imro$ed so mar(edl!+ chronic re"ection is an increasingl! common roblem • Histologicall!+ the rocess is characteri5ed b! o Atrop-* o Fibrosis o Arteriosc$erosis • &oth immune and nonimmune mechanisms are li(el! in$ol$ed %ranscribers, Angala 9 A5ul 9 &alilea 9 :austino 9 ;ere5 ;age 3 of 3