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
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
5.
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.
11.
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
13.
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.
15.
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.
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
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