Transplantation Immunology s1
Transcript of Transplantation Immunology s1
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TRANSPLANTATION
IMMUNOLOGY
.
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TRANSPLANT REJECTION
is graft failureresulting from recipient antibodiesand cellsdirected 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 similarityof 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.
TERMINOLOGY
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TRANSPLANT
SyngenicAllogenic
Xenogenic
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GRAFT
IsograftAllograft
Xenograf
Autograft
DONOR/RECIPIENT
Genetically identical (twin)Genetically nonidentical members
of some species.
Belong to different species
Graft of ones own tissues.
TYPES OF TRANSPLANTS
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
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ALLOGRAFT REJECTION
Apa yang berbeda antara sel donor
dengan sel penerima transplantasi ?
Bagaimana mekanisme respon imunpenerima menolak allograft.
Test apa yang digunakan untuk
memprediksi derajat penolakan. Bagaimana nasib allograft yang ditolak ?
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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 ?
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CLASS I Alleles
HLA-A 151
HLA-B 301
HLA-C 83
HLA-G 14
CLASS II
HLA-DR 2
HLA-DR 282
HLA-DQ 20HLA-DQ 43
HLA-DP 18
HLA-DP 87
HLA-DM 4
HLA-DM 6
HLA-DO 8
HLA-DO 3
TAP-1 6
TAP-2 4
Human leucocyte antigen (HLA) gene
complex berada di chromosome 6dengan 3 genetik region utama
berupa Class I, II dan III yang
mampu mengkode beratus-ratus gen.(Pleomorphism)
Struktur MHC memiliki persamaan
dengan 2 penangkap antigen lainny
yaitu Ig dan TCR.
(Immunoglobulin supergene family)
GENETIC & STRUCTURE OF MHC
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Self peptides
MHC Antigen
Immunocompetent
Cells
Immune response
Rejection
DONOR RECIPIENT
ALLOREACTIVITY &
TRANSPLANT REJECTION
(Allogenic MHC)
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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 MHCmolecule-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
RECOGNATION OF ALLOGENIC MHC MOLECULES
BY T LYMPHOCYTES
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ALLOGRAFT REJECTION1. HYPERACUTE REJECTION(minutes to hours)
Preexisting antibodies
Donor endothelial cells
Endothelitis
Thrombotic occlusion of the graft
Graft rejection
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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
REJECTIN
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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
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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
REJECTIN
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ALLOGRAFT REJECTION3. CHRONIC REJECTION (6 months-1 year)
FIBROSIS AND VASCULAR ABNORMALITIES
GRAFT ARTERIOSCLEROSIS
ALLOANTIGENS OF THE GRAFT
ACTIVATED CD4 TCELLS
DELAYED TYPE HYPERSENSITIVITY (DTH)
ARTERIAL OCCLUSION OF THE GRAFT
GRAFT REJECTION
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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
REJECTIN
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GRAFT VS. HOST DISEASE
This disease occurs when an immunologically competent
foreign graft containing T cellsreact against
the MHC antigens of immunologically compromised host.(it is particular concern in cases of bone marrow
transplantation).
STRAIN A DONOR
(SPLEEN CELLS)
IMMUNOSUPPRESSED
STRAIN B RECIPIENT
IMMUNOSUPRESSED
STRAIN AXB RECIPIENT
STRAIN A
DONOR CELLS DEVIDE
STRAIN A
DONOR CELLS DEVIDE
STRAIN B RECIPIENT
DIES
STRAIN AXB RECIPIENT
DIES
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CONCLUSIONS
Tissue transpants are rejected by the immunesystem, and major deteminant for rejection is MHCmolecules.
The antigen of allograft that are recognized by Tcells are allogenic MHC.
The graft antigen are either directly presented torecipent T cells, or th graft antigens are pick-up andpresented y host APCs.
Graft may be rejected by different mechanism(Hyperacute rejection, acute rejection and chronicrejection).
Graft-versus-host diseases in bone marrowtransplantation may cause temporaryimmunodeficiency of recipient.