GRAFT REJECTION

GEETA MOHAN
GRAFT REJECTION
• Transplant rejection occurs when transplanted tissue is
rejected by the recipient's immune system, which
destroys the transplanted tissue.
• Transplant rejection can be lessened by determining the
molecular similitude between donor and recipient and
by use of immunosuppressant drugs after transplant.
• The presence of a foreign tissue evokes humeral and
cellular immune response. The presence of MHC
molecules on the graft tissue evokes this response.
(The major histocompatibility complex (MHC) is a set of
cell surface proteins essential for the acquired immune
system to recognize foreign molecules in vertebrates,
which in turn determines histocompatibility)
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Types Of Graft Rejection

The time taken for graft rejection could vary depending
on the tissue or organ that has been grafted.
• If the graft is rejected within 24 hours it is called hyper
acute rejection. Such a type of rejection is seen in
xenografts. Hyper acute rejection manifests severely
and within minutes, and so treatment is immediate
removal of the tissue.
• If the graft rejection is seen after a week or ten days it
is called acute rejection. This occurs in most allografts.
• If the rejection occurs after months or years after the
acute rejection has been handled and the reaction has
subsided it is called chronic rejection.
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• Acute rejection
Developing with formation of cellular immunity, acute
rejection occurs to some degree in all transplants, except
between identical twins, unless immunosuppression is
achieved (usually through drugs).
Acute rejection begins as early as one week after transplant,
the risk being highest in the first three months, though it can
occur months to years later. Highly vascular tissues such as
kidney or liver often host the earliest signs—particularly
at endothelial cells lining blood vessels—though it eventually
occurs in roughly 10 to 30% of liver transplants, and 10 to
20% of kidney transplants .
It is believed that the process of acute rejection is mediated
by the cell mediated pathway, specifically by mononuclear
macrophages and T-lymphocytes.
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• Chronic rejection
The term chronic rejection initially described long-
term loss of function in transplanted organs
via fibrosis of the transplanted tissue's blood
vessels.
Recurrent episodes lead to chronic rejection.
Chronic rejection explains long-term morbidity in
most lung-transplant recipients, the median survival
rate is roughly 4 - 7 years .
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• . Graft rejection is primarily due to cell-mediated

immune response. The presence of the MHC
molecules on the graft tissue evokes this response.
• The presence of a foreign tissue evokes humeral
and cellular immune response.
• Different grafts show different types of reactions.
The rejection seen in a skin graft is different from
that of the kidney.
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Generally allograft rejection shows two sets of reaction

• First set reaction or primary reaction and
• Secondary set reaction

• The first set reaction or primary reaction occurs after a few

days of grafting. If it is a skin graft several days are required
for the blood vessels and lymph vessels to make connections
between the host tissue and the graft. Only after the
leucocytes enter in does rejection set in.
• The first sign of rejection is the accumulation of neutrophils
around the blood vessels at the base of the graft. The
macrophages and lymphocytes invade the graft. The
endothelium of the graft is destroyed and there is formation
of blood clots that seals the blood capillaries shutting off the
blood supply. This results in the death of the graft tissue.
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The secondary set reaction occurs when a second graft

is inserted and the rejection is faster. In the skin graft
the blood vessels do not get sufficient time to grow.
• If it is a kidney or a heart or a liver transplant the first
set reactions are different. The blood vessels are
already connected during the surgery. The lymphocytes
and monocytes invade the new organ. This endothelial
lining of the blood vessels is damaged, blood flow is
blocked, and tissue is destroyed because of formation
of blood clots.
• The secondary set reaction that occur in the above
mentioned organ transplant are rapid blocking of the
blood vessels due to the action of antibodies and the
complement on the endothelial lining of the blood
vessels.
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Mechanism of Graft Rejection

The first set reaction in graft rejection involves two
phases,
A. Sensitization phase
B. Effector phase
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A. Sensitization phase
• This is the first step in graft rejection. The antigen on the
allograft provokes the proliferation of the T lymphocytes.
The immune system of the recipient recognizes the MHC
molecules (major histocompatibility complex ) on the graft tissue.
• There is also the recognition of an associated peptide
molecule in the groove of the allogenic class I MHC
molecule which is produced inside the cell.
• CD4+ and CD8+ (cluster of differenciation ) cells recognize
alloantigens expressed on cells of foreign graft and
induces T cell proliferation in the host
• In some grafts such as kidney and pancreas the donor
antigen presenting cells (ACP) or dendritic cells are called
passenger leucocytes because they migrate from the graft
to the lymph node of that region. The passenger
leucocytes have excess dose of MHC class II molecules
and a normal dose of class I MHC molecule. This
stimulates the T cells in the lymph node. The T cells are
responsible for the other effector immune responses.
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B. Effector phase
• The second step in graft rejection involves the
following processes-
• There is delayed type hypersensitivity.
• Cytotoxic T lymphocytes mediated cytotoxicity.
• Antibody –antigen reaction and complement lysis.
• Destruction caused by cell mediated cytotoxicity.
• There is entry of T cells and macrophages. There is
production of cytokines by T cells.
The immune responses mentioned above cause the
destruction of graft tissue
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Causes for graft rejection

One principal reason for transplant rejection is non-
adherence to prescribed immunosuppressant regimens.
This is particularly the case with adolescent
recipients, with non-adherence rates near 50% in some
instances.
Diagnosis of acute rejection relies on clinical data
,patient signs and symptoms and three
main histological signs:
(1) Infiltrating T cells, perhaps accompanied by
infiltrating eosinophils, plasma cells, and neutrophils
(2) Structural compromise of tissue anatomy, varying by
tissue type transplanted
(3) Injury to blood vessels .
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Graft rejection

Reference / Acknowledgement

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