Transplantation immunology

All info regarding transplantation and its immunity

1. TRANSPLANTATION IMMUNOLOGY
Chartha. Gaglani.

2. CONTENTS
1)Introduction
2)Transplantation immunity
3)Autograft
4)Allograft
5)Xenograft
6)ABO Incompatible
7)Rejection
8)HLA Tissue typing

3. INTRODUCTION
•Organtransplantationisoftentheonlytreatmentforend
stateorganfailure,suchasliverandheartfailure.
•Althoughendstagerenaldiseasepatientscanbetreated
throughotherrenalreplacementtherapies,kidney
transplantationisgenerallyacceptedasthebesttreatment
bothforqualityoflifeandcosteffectiveness.
•Kidneytransplantationisbyfarthemostfrequently
carriedouttransplantationglobally.
•Theprocurementoforgansfortransplantationinvolves
theremovaloforgansfromthebodiesofdeceased
persons.

4. •Thisremovalmustfollowlegalrequirements,including
thedefinitionofdeathandconsent.
•Kidneydonationbywellselectedlivingdonorswithgood
healthcoveragecarriesnegligiblerisks.
•Thiscanonlybeensuredthroughrigorousselection
procedures,carefulsurgicalnephrectomyandfollowup
ofthedonortoensuretheoptimalmanagementof
untowardconsequences.

5. Kidney
transplant
Heart
transplant

6. TRANSPLANTATION IMMUNITY
•Theimmunesystemplaysacriticalroleintransplantation.Thecomplex
mechanismsofimmunity,whichundernormalcircumstancesworkto
identifyforeignmicrobesanddirecttheimmunesystemtodestroythem,
poseasignificantbarriertosuccessfultransplantation.
•Rejectionofatransplantoccursininstanceswheretheimmunesystem
identifiesthetransplantasforeign,triggeringaresponsethatwillultimately
destroythetransplantedorganortissue.
•Toreducethepossibilityofrejection,thedonorandrecipientarecarefully
matchedforimmunecompatibilitypriortotransplantation.
•However,thesmallpoolofeligibledonorscanmakeitdifficulttofinda
donor-recipientmatchandtherewillalwaysbeadegreeofrejectionagainst
thegraft.
•Acriticalundersupplyofdonatedorgansmeansthatwaitinglistsfor
transplantsareextremelylong.

7. •Patientsneedingakidneytransplantation,forexample,waiton
average944days(morethantwoandahalfyears)foralife-
savingtransplant.
•Severaltypesoftissueandorgantransplantationoccurring:
1.Autograft
2.Allograft
3.Xenograft
4.ABOincompatible

9. AUTOGRAFT
•Transplantationofcells,tissuesororgansbetween
siteswithinthesameindividuale.g.skingraft.

10. ALLOGRAFT
•Transplantation of organs or tissues from a donor to a
non-genetically identical individual of the same
species.
•Allografts are the most common type of transplant.

11. XENOGRAFT
•Transplantationofanorganortissuebetweentwodifferent
species.
•‘Pigvalves’,forexample,arecommonlyusedtorepairor
replaceadefectiveheartvalveinhumans.

12. ABO INCOMPATIBLE
•ABOreferstobloodgroup,whichcanvarybetween
individuals.
•Formosttransplanttypes,matchingofbloodgroupbetween
donorandrecipientisakeystrategyinreducingrejectionrisk.
•However,bloodgroupcompatibilityisnotalwaysrequiredfor
transplantations.
•Forexample,inthecaseofveryyoungchildrenwithimmature
immunesystems,ABOincompatibletransplantscanbecarried
outwithlessriskoftransplantrejection.

13. HYPERACUTE REJECTION
•Thisoccurswithinminutesorhoursafteratransplantation
andiscausedbythepresenceofpreexistingantibodiesof
therecipient,thatmatchtheforeignantigensofthedonor,
triggeringanimmuneresponseagainstthetransplant.
•Theseantibodiescouldhavebeengeneratedasaresultof
priorbloodtransfusions,priortransplantationsormultiple
pregnancies.
•Theantibodiesreactwithcellsinthebloodvesselsofthe
graft,causingbloodclotstoform,whichwillpreventblood
supplyfromreachingthegraftresultinginimmediate
rejectionofthetransplant.

14. ACUTE REJECTION
•Thisoccurswithinthefirst6monthsaftertransplantation.
•Somedegreeofacuterejectionwilloccurinalltransplantations,
exceptbetweenidenticaltwins.
•Recipientsaremostatriskinthefirst3months,butrejectioncan
stilloccuratalaterstage.
•Acuterejectioniscausedbytheformationofantibodiesfollowing
thedetectionofnon-selfantigensinthedonatedgraft.
•Ifdiagnosedearlyenough,acuterejectioncanbetreatedby
suppressingtheimmunesystemandpermanentdamagetothegraft
canbeavoidedinsomecases.

15. CHRONIC REJECTION
•Repeatedepisodesofacuterejectioncanultimatelyleadto
chronicrejectionofthegraftandfailureofthetransplant.
•Chronicrejectioncommonlymanifestsasscarringofthetissue
ororganwhichcanoccurmonthstoyearsafteracuterejection
hassubsided.
•Atpresent,thereisnocureforchronicrejectionotherthan
removalofthegraft.

16. IMMUNOSUPPRESSIVE DRUGS
•Toreducetheriskoftransplantrejection,patientsaretreatedwith
immunosuppressivedrugsthatwilldampentheirimmuneresponse.
•Immunosuppressivedrugsaregivenintwophases;aninitialinduction
phaseinvolvingahighdose,andalatermaintenancephasewhichinvolves
usingthedruginthelongtermatalowerdose.
•Thecombinationofdrugs,anddosagegiven,willvarydependingonthe
typeoftransplantandthechosentreatmentregime.
•Ifapatientexperiencesanepisodeofacuterejectionthedrugcombination
issubjecttochangeandthedosageisalsolikelytoincrease.
•Sideeffectscanalsocausealternativedrugstobeused.Steroids,inthe
past,havebeenthemostcommonlyusedimmunosuppressantdrug.
•However,theiruseisbeingreducedduetotheadversesideeffects
associatedwiththem.

17. HLA TISSUE TYPING
•WhentwopeoplesharethesameHumanLeukocyteAntigens
(abbreviatedasHLA),theyaresaidtobea"match",thatis,their
tissuesareimmunologicallycompatiblewitheachother.
•HLAareproteinsthatarelocatedonthesurfaceofthewhiteblood
cellsandothertissuesinthebody.
•TherearethreegeneralgroupsofHLA,theyareHLA-A,HLA-B
andHLA-DR.
•TherearemanydifferentspecificHLAproteinswithineachofthese
threegroups.(Forexample,thereare59differentHLA-Aproteins,
118differentHLA-Band124differentHLA-DR.Eachofthese
HLAhasadifferentnumericaldesignation.)

18. •InthediagramabovewecanseehowachildinheritsoneHLAineachgroup,from
his/herparents.

19. •IftwochildreninherittheverysameHLAfromtheirparents,
theyareanHLA"identicalmatch".Whileanotherchildinthe
samefamilycaninheritadifferentcombinationofHLA:Itis
importanttoknowthatHLAisinheritedasa"set"ofthethree
HLAgroups,A,B,DR.
•Thissetisknownasa"haplotype".
This child does not match at
all with his/her sibling.

20. •Father has 2 distinct
HLA haplotypes.

21. •Youinheritonehaplotypefromeachparent.
•Therefore,thereareatotaloffourdifferenthaplotypecombinations
from2parents.
•ThereisabasicruleinHLAinheritance.Theruleis:youhavea
25%chanceofinheritingallofthesameHLA(same2haplotypes)
asanyoneofyoursiblings,youhavea25%chanceofnotinheriting
anyofthesameHLA(noneofthesamehaplotypes)andyouhavea
50%chanceofsharingIhaplotypewithyoursiblings.
•Therefore,youhavea1in4chanceofbeinganidenticalmatchwith
yoursiblings.
•AfterHLAisdetermined,thereisasecondtestwhichwillindicate
ifthereisspecificimmunereactivitybetweenthedonorand
recipient.Thistestisthe"crossmatch".

23. THANK YOU…