TRANSPLANTATION

IMMUNOLOGY
.
 TERMINOLOGY
TRANSPLANT REJECTION
is graft failure resulting from recipient antibodies and cells
directed against donor cells

TISSUE COMPATIBILITY
- the need for donor and rescipient tissue to be compatible
in order for a transplat to be accepted.
- It depend upon genetic similarity of donor and recipient

HISTOCOMPATIBILITY ANTIGEN
Genetic similarity between transplant donor and recipient
(histocompatibility) is encoded by two set of genes namely
major histocompatibility complex (MHC) and
minor histocompatibility antigens.
 TYPES OF TRANSPLANTS

TRANSPLANT GRAFT DONOR/RECIPIENT

Syngenic Isograft Genetically identical (twin)
Allogenic Allograft Genetically nonidentical members
of some species.
Xenogenic Xenograf Belong to different species
--------------- Autograft Graft of one’s own tissues.

DONOR RECIPIENT TYPE OF TRANSPLANT

TRANSPANT OUTCOME

STRAIN A STRAIN A SYNGENIC ACCEPTANCE

STRAIN B STRAIN A ALLOGENIC REJECTION
STRAIN B STRAIN AXB (F1) SYNGENIC ACCEPTANCE
STRAIN AXB(F1) STRAIN B ALLOGENIC REJECTION
 ALLOGRAFT REJECTION

• Apa yang berbeda antara sel donor

dengan sel penerima transplantasi ?
• Bagaimana mekanisme respon imun
penerima menolak allograft.
• Test apa yang digunakan untuk
memprediksi derajat penolakan.
• Bagaimana nasib allograft yang ditolak ?
 ALLOGRAFT REJECTION
• What is the difference between donor
tissue and recipient tissue. ?
• How does mechanism of graft rejection
by immune responses of the recipient.?
• What kind of test may be used to
predict the grade of rejection. ?
• How does the fate of rejected graft ?
CLASS I Alleles GENETIC & STRUCTURE OF MHC
HLA-A 151
HLA-B 301
HLA-C 83
Human leucocyte antigen (HLA) gene
HLA-G 14 complex berada di chromosome 6
CLASS II dengan 3 genetik region utama
HLA-DRα 2
HLA-DRß 282
berupa Class I, II dan III yang
HLA-DQα 20 mampu mengkode beratus-ratus gen.
HLA-DQß 43 (Pleomorphism)
HLA-DPα 18
HLA-DPß 87
HLA-DMα 4 Struktur MHC memiliki persamaan
HLA-DMß 6 dengan 2 “penangkap antigen” lainnya
HLA-DOα 8 yaitu Ig dan TCR.
HLA-DOß 3
TAP-1 6 (Immunoglobulin supergene family)
TAP-2 4
 ALLOREACTIVITY &
TRANSPLANT REJECTION
DONOR RECIPIENT
Immune response

Rejection

Immunocompetent
MHC Antigen Cells
(Allogenic MHC)
Self peptides
RECOGNATION OF ALLOGENIC MHC MOLECULES
BY T LYMPHOCYTES

Figure 16-4 Molecular basis of

direct recognition of allogeneic
MHC molecules. Direct
recognition of allogeneic MHC
molecules may be thought of as
a cross-reaction in which a T
cell specific for a self MHC
molecule-foreign peptide
complex (A) also recognizes an
allogeneic MHC molecule (B, C).
Nonpolymorphic donor
peptides, labeled "self peptide,"
may not contribute to
allorecognition (B), or they may
(C).

Downloaded from: StudentConsult (on 20 November 2007 06:33 AM)

© 2005 Elsevier
 ALLOGRAFT REJECTION
1. HYPERACUTE REJECTION(minutes to hours)
Preexisting antibodies

Donor endothelial cells

Endothelitis

Thrombotic occlusion of the graft

Graft rejection
ALLOGRAFT
REJECTIN

Figure 16-7 Immune mechanisms of graft rejection. A. In hyperacute rejection, preformed antibodies reactive with vascular endothelium activate complement and trigger
rapid intravascular thrombosis and necrosis of the vessel wall. B. In acute rejection, CD8+ T lymphocytes reactive with alloantigens on endothelial cells and parenchymal
cells mediate damage to these cell types. Alloreactive antibodies formed after engraftment may also contribute to vascular injury. C. In chronic rejection with graft
arteriosclerosis, injury to the vessel wall leads to intimal smooth muscle cell proliferation and luminal occlusion. This lesion may be caused by a chronic DTH reaction to
alloantigens in the vessel wall.

Downloaded from: StudentConsult (on 20 November 2007 06:33 AM)

© 2005 Elsevier
 ALLOGRAFT REJECTION

2. ACUTE REJECTION (first week)

ALLOANTIGEN IN THE GRAFT

ACTIVATED HOST T CELL AND ANTIBODIES

VASCULAR AND PARENCHYMAL INJURY OF THE GRAFT

GRAFT REJECTION
ALLOGRAFT
REJECTIN

Figure 16-7 Immune mechanisms of graft rejection. A. In hyperacute rejection, preformed antibodies reactive with vascular endothelium activate complement and trigger
rapid intravascular thrombosis and necrosis of the vessel wall. B. In acute rejection, CD8+ T lymphocytes reactive with alloantigens on endothelial cells and parenchymal
cells mediate damage to these cell types. Alloreactive antibodies formed after engraftment may also contribute to vascular injury. C. In chronic rejection with graft
arteriosclerosis, injury to the vessel wall leads to intimal smooth muscle cell proliferation and luminal occlusion. This lesion may be caused by a chronic DTH reaction to
alloantigens in the vessel wall.

Downloaded from: StudentConsult (on 20 November 2007 06:33 AM)

© 2005 Elsevier
 ALLOGRAFT REJECTION
3. CHRONIC REJECTION (6 months-1 year)
ALLOANTIGENS OF THE GRAFT
ACTIVATED CD4 T CELLS

DELAYED TYPE HYPERSENSITIVITY (DTH)

FIBROSIS AND VASCULAR ABNORMALITIES

GRAFT ARTERIOSCLEROSIS

ARTERIAL OCCLUSION OF THE GRAFT

GRAFT REJECTION
ALLOGRAFT
REJECTIN

Figure 16-7 Immune mechanisms of graft rejection. A. In hyperacute rejection, preformed antibodies reactive with vascular endothelium activate complement and trigger
rapid intravascular thrombosis and necrosis of the vessel wall. B. In acute rejection, CD8+ T lymphocytes reactive with alloantigens on endothelial cells and parenchymal
cells mediate damage to these cell types. Alloreactive antibodies formed after engraftment may also contribute to vascular injury. C. In chronic rejection with graft
arteriosclerosis, injury to the vessel wall leads to intimal smooth muscle cell proliferation and luminal occlusion. This lesion may be caused by a chronic DTH reaction to
alloantigens in the vessel wall.

Downloaded from: StudentConsult (on 20 November 2007 06:33 AM)

© 2005 Elsevier
GRAFT VS. HOST DISEASE
This disease occurs when an immunologically competent
foreign graft containing T cells react against
the MHC antigens of immunologically compromised host.
(it is particular concern in cases of bone marrow
transplantation).

STRAIN A DONOR
(SPLEEN CELLS)

IMMUNOSUPPRESSED IMMUNOSUPRESSED
STRAIN B RECIPIENT STRAIN AXB RECIPIENT

STRAIN A STRAIN A
DONOR CELLS DEVIDE DONOR CELLS DEVIDE

STRAIN B RECIPIENT STRAIN AXB RECIPIENT

DIES DIES
 CONCLUSIONS
• Tissue transpants are rejected by the immune
system, and major deteminant for rejection is MHC
molecules.
• The antigen of allograft that are recognized by T
cells are allogenic MHC.
• The graft antigen are either directly presented to
recipent T cells, or th graft antigens are pick-up and
presented by host APCs.
• Graft may be rejected by different mechanism
(Hyperacute rejection, acute rejection and chronic
rejection).
• Graft-versus-host diseases in bone marrow
transplantation may cause temporary
immunodeficiency of recipient.