Graft Rejection

‫بسم ال الرحن الرحيم‬

Faculty of .medicine Alexandria .university Department of .pathology

Graft rejection

:0bjectives .Introduction.1 .Types of transplantation.2 .Graft rejection.3 .Causes of graft rejection.4 .Mechanism of graft rejection.5 .Types of graft rejection .6 .Treatment of graft rejection.7

: Transplantation Transferring cells, tissues, or organs from one site to another

Types of :transplantation

.Autologous graft = auto graft .Synegenic graft = syngraft .Allogeneic graft = allograft .Xenogenic graft = xenogaft

:Graft rejection Occurs when a transplanted organ or tissue fails to be accepted by the body of the .transplant recipient

Causes of :graft rejection Pleomorphism of MHC genes Different MHC Ags within species& individuals T Lymphocytes recognize transplanted organ as .foreign& release cytokines that lyse cells

Graft failure

echanism of graft rejectio

)T Cell Mediated )Ce .Dire .Indire 2.Antibody Mediated Reactions )Humoral rejection(

Mechanism of :graft rejection

)T Cell Mediated )Cellular rejection.1:

CD4 CD8 cells + .Lysis of grafted tissue

cytokine inflammation mononuclear cells

:Types of T cell mediated reaction

1. Direct Pathway:

 T cells of recipient recognize allogenic MHC molecule on the surface of an APC in donor.  interstitial dendritic cells of donor organs are the best immunogenic.(why?)  CD4+ and CD8+ T cells of recipient encounter antigens in lymph nodes  CD4+ proliferate, release cytokines& trigger delayed hypersensitivity reaction.  Cytokines vascularity &induceinflammation.  mature CTLs are generated and lyse grafted tissue .

:Indirect pathway .2 recipient T lymphocytes recognize antigens after being presented by own antigenpresenting cells. same as presentation of microbial antigens.

2.Antibody Mediated Reactions : )Humoral rejection( 1. In Hyperacute reaction:  

previous exposure to the donor antigens. As in: previous rejected kidney transplant. Multiparous women. Previous blood transfusion.

2. In chronic rejection:  

not previously exposed to the donor antigen. Abs cause damage by complement, ADCC &Ag Ab complex

Types of graft :rejection

.a) Hyper acute = immediate .b) Acute = cellular .c) Chronic = fibrosis

Hyper acute :rejection Reaction : due to (

complement + preexisting antibodies as (ABO) (humoral

:Time .occurs within minutes to hours

:Complication .Rapid thrombosis, no vascularization .Infarcts . Acute systemic inflammation

:Prognosis .Organ is removed

:Steps involved

Morphology of hyper acute In hyper acutely rejecting kidney  Grossly:



cyanotic, mottled, flaccid and may excrete few drops of bloody urine Microscopically: Acute necrotizing vasculitis. Neutrophil accumulation. Platelet aggregation. Complements activation &endothelial damage.

:Hyper acute rejection

:Acute rejection :Reaction

.cellular: Primary activation of T cells .humoral&

:Time ..weeks after transplantation :Complication (organ failure (mainly in vascularized organs .recurrent episodes chronic rejection

:Prognosis .treatable

Acute rejection

Diagnosis: .

signs& symptoms. Lab diagnosis& tissue biopsy

Morphology of acute rejection: There isacute cellular rejection .T lymphocyte infiltration .1 .injury of the tissue .2 injury of organ bood vessels .3 

:Chronic rejection Reaction: cellular .chronic immune response .fibrosis of internal blood vessels (allograft vasculopathy) :Time .along years :Complication .loss of function gradually :Prognosis need anew transplant usually after a decade

:Morphology of chronic rejection   

Loss of function in transplanted organs termed chronic allograft vasculopathy Grossly

vascular changes: of dense intimal fibrosis in the cortical arteries& renal ischemia glomerular loss and tubular atrophy shrinkage of renal parenchyma. 

Microscopically:

vascular lesions mononuclear cell infiltrates

Chronic kidney rejection

:Treatment :a) Hyperacute rejection only by removal of the organ immediately

:b) Chronic rejection .irreversible & cannot be prevented only treatment is a new transplant after .years 10

:c) Acute rejection .high dose corticosteroids.1 Not enough

.repeated.2 Not enough

.tripple therapy.3

:Triple therapy .Corticosteroids e.g Cyclosporin A.1 .Calcineurin inhibitor.2 . Antiproliferative agent.3 :plus .antibodies against blood vessels blood transfusion remove antibodies& . against the transplant

Graft associated immune :suppression :corticosteroids.1 .lyse mature T cells Dnase + cytokine synthesis IL1, IL6& TNF

:Metabolic toxins.1 .lymphocyte growth :as Azathioprine Cyclophosphamide Cyclosporin Calcineurin :Irradiation.2

:Induce tolerence.4 .by multiple blood transfusion :Antibodies.5 .against T cell surface proteins .monoclonal Ab against CD3 .antibodies against b cells Can also remove Ab by plasmapheresis

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