‫بسم ال الرحن الرحيم‬

Faculty of
.medicine
Alexandria
.university
Graft
Department of
.pathology
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 + cytokine

inflammation
.Lysis of grafted tissue
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 antigen-
presenting 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
Thank
..…you