Transplantation immunology

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

Transplantation immunology

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