Note: Texts colored MAROON are from Schwartzs

(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