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Rinkesh Joshi
M.Sc Sem : 3
Bioscience ( Micro)
09924113838
Surat,
Gujarat.
History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
 1944 : Medawar showed that skin allograft
rejection is a host versus graft response.
 1954 : The first successful identical twin
transplant of a human kidney was
performed by Joseph E. Murray in Boston
 1967 : The first successful liver transplant was done
by Dr. Thomas E. Starzl
 1967 : The first heart transplantation by Christian
Barnard
 1968 : The first successful bone marrow transplant
was done by E. Donnall Thomas
Transplantation is a act of transferring
cells, tissue, or organ from one site to another
Graft : Implanted cell, tissue or organ
Donor : Individual who provides the graft
Recipient or host : Individual who receives the
graft
 Self tissue is transferred from one body site to
another
 Antigen present in autograft is same as that present
in body
 So immune system recognizes the autograft antigen
as a self antigen
 No immune response is elicited
 Autograft survive through out the life
 Eg., - Transferring healthy skin to burned
area,
- Use of healthy blood vessels to
replace blocked coronary arteries,
- Plastic surgery of skin.
It is also called syngraft
Tissue is transferred between
genetically identical individuals of
same species
In isograft the histo compatibility
antigens are identical hence the
graft survives and not rejected.
Eg in human isograft can be
performed between two twins.
Tissue is transferred between two genetically
different members of same species
In allograft histocompatibility antigens are
dissimilar hence immune response is elicited
and graft is rejected
Eg., In humans graft is transferred from one
individual to another
Tissue is transferred between two different
species
Eg., Graft of human transferred to animal
In xenografts histocompatibility complex
antigens are so different that the graft is
more vigorously rejected
• Alloantigens elicit both cell-mediated and
humoral immune responses.
• Recognition of transplanted cells that are self
or foreign is determined by polymorphic
genes that are inherited from both parents
and are expressed co-dominantly.
Rate of allograft rejection varies according to
tissue involved
Skin graft are rejected faster than other tissue
organ kidney or heart
If inbred mouse of strain A is grafted with skin
from strain B , Primary graft rejection occur called
first set rejection
When again strain A is grafted with skin from
strain B , Secondary graft rejection occur called
second set rejection
Direct recognition of Alloantigens
host T cells recognize intact allo-MHC molecules
on the surface of the donor cell.
host T cells see allo-MHC molecule + allo-peptide
as being equivalent in shape to self-MHC +
foreign peptide and hence recognize the donor
tissue as foreign.
This pathway is the dominant pathway.


Indirect recognition of Alloantigens
Donor MHC is processed and presented by
recipient APC
Basically, donor MHC molecule is handled like any
other foreign antigen
Donor APCs migrate to regional lymph nodes
and are recognized by the recipient’s T cells
Alloreactive T cells in the recipient may be
activated and they migrate into the graft and
cause graft rejection
Used by immune system to reject allograft
It is based on histopathological features or time
duration of rejection after transplantation

There are three type of patterns
1. Hyperacute Rejection
2. Acute Rejection
3. Chronic Rejection
 Graft is rejected within minutes to hours because
vascularization is rapidly destroyed.
 It occurs because the recipient has pre-existing
antibodies in circulation against the graft.
 Which could be induced by prior blood
transfusions, multiple pregnancies, prior
transplantation, or xenografts.
 Antibodies bind with donor endothelial cell.
 The antigen-antibody complexes activate the
complement system, causing massive thrombosis in
the capillaries, which prevents the vascularization of
the graft.
 The kidney is most susceptible to hyperacute
rejection.
1)
2)
3)
4)
5)

Preformed Ab,
complement activation,
Neutrophil margination,
Inflammation,
Thrombosis formation.
 Vascular and parenchymal injury mediated by T
cells and antibodies that usually begin after the
first week of transplantation if there is no
immunosuppressant therapy
 Antibodies from after transplantation may also
contribute to vascular injury.
Occurs in most solid organ transplants
o Heart
o Kidney
o Lung
o Liver

Characterized by fibrosis and vascular
abnormalities with loss of graft function over a
prolonged period
Arthrosclerosis
Cell proliferation
Occlusion
I.
II.
III.
IV.

Blood grouping
Cytotoxic antibody testing
Tissue matching
Immunosuppressive drugs
(azathioprine,cyclosporine,rapamycin, cortic
osteroids)
In some instance the graft tissue elicits an
immune response against host antigen and
that immune response is called graft versus
host reaction
Graft versus host reaction brings damage to
host cells and host
When grafted tissue has mature T cells, they
will attack host tissue leading to GVHR.
Graft lymphocytes aggregate in the host
lymphoid organs
Graft lymphocytes are stimulated by the host
lymphocyte
Stimulated lymphocytes of graft produce
lymphokines
Lymphokines activate host T- cell which produce
polyclonal b-cell activation
Activated b-cell react with the self antigens and
cause damage to the host cell
Skin rash
Emaciation ( becoming thin)
Retarded growth
Diarrhoea
Hepatomegaly
Splenomegaly
Increase in bilirubin production
Bileducts are damaged
anaemia
History and Types of Graft Rejection in Transplantation
History and Types of Graft Rejection in Transplantation

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History and Types of Graft Rejection in Transplantation

  • 1. Rinkesh Joshi M.Sc Sem : 3 Bioscience ( Micro) 09924113838 Surat, Gujarat.
  • 2. History Introduction Classification of grafts The Immunology of Allogeneic Transplantation Genetics of graft rejection Types of rejection Recognition of Alloantigens Effector Mechanisms of Allograft Rejection Prevention of graft rejection Graft versus host reaction
  • 3.  1944 : Medawar showed that skin allograft rejection is a host versus graft response.  1954 : The first successful identical twin transplant of a human kidney was performed by Joseph E. Murray in Boston  1967 : The first successful liver transplant was done by Dr. Thomas E. Starzl  1967 : The first heart transplantation by Christian Barnard  1968 : The first successful bone marrow transplant was done by E. Donnall Thomas
  • 4. Transplantation is a act of transferring cells, tissue, or organ from one site to another Graft : Implanted cell, tissue or organ Donor : Individual who provides the graft Recipient or host : Individual who receives the graft
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  • 6.  Self tissue is transferred from one body site to another  Antigen present in autograft is same as that present in body  So immune system recognizes the autograft antigen as a self antigen  No immune response is elicited  Autograft survive through out the life  Eg., - Transferring healthy skin to burned area, - Use of healthy blood vessels to replace blocked coronary arteries, - Plastic surgery of skin.
  • 7. It is also called syngraft Tissue is transferred between genetically identical individuals of same species In isograft the histo compatibility antigens are identical hence the graft survives and not rejected. Eg in human isograft can be performed between two twins.
  • 8. Tissue is transferred between two genetically different members of same species In allograft histocompatibility antigens are dissimilar hence immune response is elicited and graft is rejected Eg., In humans graft is transferred from one individual to another
  • 9. Tissue is transferred between two different species Eg., Graft of human transferred to animal In xenografts histocompatibility complex antigens are so different that the graft is more vigorously rejected
  • 10. • Alloantigens elicit both cell-mediated and humoral immune responses. • Recognition of transplanted cells that are self or foreign is determined by polymorphic genes that are inherited from both parents and are expressed co-dominantly.
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  • 12. Rate of allograft rejection varies according to tissue involved Skin graft are rejected faster than other tissue organ kidney or heart If inbred mouse of strain A is grafted with skin from strain B , Primary graft rejection occur called first set rejection When again strain A is grafted with skin from strain B , Secondary graft rejection occur called second set rejection
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  • 14. Direct recognition of Alloantigens host T cells recognize intact allo-MHC molecules on the surface of the donor cell. host T cells see allo-MHC molecule + allo-peptide as being equivalent in shape to self-MHC + foreign peptide and hence recognize the donor tissue as foreign. This pathway is the dominant pathway.
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  • 16.  Indirect recognition of Alloantigens Donor MHC is processed and presented by recipient APC Basically, donor MHC molecule is handled like any other foreign antigen
  • 17. Donor APCs migrate to regional lymph nodes and are recognized by the recipient’s T cells Alloreactive T cells in the recipient may be activated and they migrate into the graft and cause graft rejection
  • 18. Used by immune system to reject allograft It is based on histopathological features or time duration of rejection after transplantation There are three type of patterns 1. Hyperacute Rejection 2. Acute Rejection 3. Chronic Rejection
  • 19.  Graft is rejected within minutes to hours because vascularization is rapidly destroyed.  It occurs because the recipient has pre-existing antibodies in circulation against the graft.  Which could be induced by prior blood transfusions, multiple pregnancies, prior transplantation, or xenografts.  Antibodies bind with donor endothelial cell.  The antigen-antibody complexes activate the complement system, causing massive thrombosis in the capillaries, which prevents the vascularization of the graft.  The kidney is most susceptible to hyperacute rejection.
  • 20. 1) 2) 3) 4) 5) Preformed Ab, complement activation, Neutrophil margination, Inflammation, Thrombosis formation.
  • 21.  Vascular and parenchymal injury mediated by T cells and antibodies that usually begin after the first week of transplantation if there is no immunosuppressant therapy  Antibodies from after transplantation may also contribute to vascular injury.
  • 22. Occurs in most solid organ transplants o Heart o Kidney o Lung o Liver Characterized by fibrosis and vascular abnormalities with loss of graft function over a prolonged period
  • 24. I. II. III. IV. Blood grouping Cytotoxic antibody testing Tissue matching Immunosuppressive drugs (azathioprine,cyclosporine,rapamycin, cortic osteroids)
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  • 26. In some instance the graft tissue elicits an immune response against host antigen and that immune response is called graft versus host reaction Graft versus host reaction brings damage to host cells and host When grafted tissue has mature T cells, they will attack host tissue leading to GVHR.
  • 27. Graft lymphocytes aggregate in the host lymphoid organs Graft lymphocytes are stimulated by the host lymphocyte Stimulated lymphocytes of graft produce lymphokines Lymphokines activate host T- cell which produce polyclonal b-cell activation Activated b-cell react with the self antigens and cause damage to the host cell
  • 28. Skin rash Emaciation ( becoming thin) Retarded growth Diarrhoea Hepatomegaly Splenomegaly Increase in bilirubin production Bileducts are damaged anaemia