Transplantation Immunology s1

8/10/2019 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

---------------

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.


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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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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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.

Transplantation Immunology s1

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