Dr. Fairuz Quzwain, SpPA, M.

Kes
Bagian Patologi Anatomi
Program Studi Pendidikan Dokter
Universitas Jambi
 A Major barrier to transplantation is the process of
rejection

 Rejection  the recepient’s immune system

recognizes the graft as being foreign and attacks it

 Skin, Kidneys, heart, lungs, liver, spleen, bone marrow

and endocrine organs.
Mechanisms
 The antigens responsible for such rejection in humans
are those of the HLA system

 Every individual will recognize some HLA molecules

in another individual as foreign

 Rejection is a complex process in which both cell-

mediated immunity and circulating antibodies play a
role
T cell-mediated Reaction
 Called cellular rejection

 Induced by 2 mechanism :
1. destruction of graft cells by CD8+ CTLs
2. delayed hypersensitivity by CD4+ helper

 The recipient’s T cell recognize antigens in graft bay 2

pathways, called direct and indirect
 The direct pathway is the major pathway in acute
cellular rejection, whereas the indirect pathway is
more important in chronic rejection.
Antibody-mediated Reaction
 Called humoral rejection

 Hyperacute rejection occurs when preformed antidonor

antibodies are present in the circulation of the recipient.
- Kidney transplantation
- Blood transfusions

 When preformed antidonor antibodies are present,

rejection occurs immediately after transplantation because
the circulating antibodies react with and deposit rapidly on
the vascular endothelium of the grafted organ
 Complement fixation occurs, resulting in thrombosis
of vessels in the graft and ischemic death of the graft.
 The initial target of these antibodies in rejection
appears to be the graft vasculature  vasculitis
Morphology
 On the basis of the morphology and the underlying
mechanism, rejection reactions are classified as :
Hyperacute, Acute , and Chronic
 Hyperacute :
- Occurs within minutes or hours
- Ig and Compl are deposited in the vessel wall
( endothelium)
- ex. Kidney : cyanotic, mottled, flaccid, excretes mere
few drops of bloody urine
 Acute :
- Occurs within days in the untreated recipient or may
appear suddenly months or even years later after
immunosupression has been employed and
terminated
- Vasculitis, interstitial mononuclear cell infiltrate
 Chronic :
- in recent years, acute rejection has been significantly
controlled by immunosupressive therapy, and chronic
rejection has emerged as an important cause of graft
failure.
- Dominated by vascular changes, intstitial fibrosis and
atrophy.
- The vascular changes consist of dense, obliterative
intimal fibrosis.
Increasing Graft Survival
 Minimizing the HLA disparity between the donor and
the recipient would be expected to improve graft
survival.
 Immunosupressive therapy  cyclosporine