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Transplantation Immunity
Transplant immunology
• Transplant immunology is the study of the immune
response that occurs when an organ or tissue is moved
(grafted) from one individual to another.
• Transplantation is the process of moving cells, tissues or
organs from one site to another or from one individual to
another for the purpose of repairing damaged or diseased
organs.
• A major problem following transplantation is that the immune
system of the recipient sees the grafted tissue as ‘foreign’ and
attacks and destroys it.
• Types of tissue graft:
• Autograft –Transplantation of cells, tissues or organs
between sites within the same individual e.g. skin graft.
•Syngeneic graft is a transfer of tissue between
genetically identical individuals, i.e., identical twins
• Allograft – Transplantation of organs or tissues from a
donor to receipient a non-genetically identical individual of
the same species. Allografts are the most common type of
transplant.
• Xenograft – Transplantation of an organ or tissue between
two different species. ‘Pig valves’, for example, are
commonly used to replace a defective heart valve in humans.
May take place between:
 different parts of the same
organism (auto-grafting)
 different organisms of the same
species (allo-grafting)
 different species
(xeno-grafting)
Methods of Transplantation:
Autografting
• The transfer of self tissue from
one body site to another in the
same individual
• Due to the genetic homology of
the tissue, the immune system
does not respond to it
• Examples
 Skin grafts
 Bone marrow transplantation
 Hair
Allografting
Definition: It is a graft between genetically
different members of the same species
(human to human).
• Allografts are usually rejected unless the
recipient is given immunosuppressive drugs
• The severity and rapidity of the rejection
will depending on the degree of the
differences between the donor and the
recipient at the MHC loci.
Xenografting
Definition: Xenotransplantation –
the transfer of tissue from one
species to another (animal tissue in
humans)
• It is always rejected by an immunocompetent
recipient.
• Still under trials.
• Xenotransplantation of whole organs is not
currently viable.
• Pig valves’, for example, are commonly used
to repair or replace a defective heart valve in
humans
Graft Rejection
• Graft rejection occurs when the recipient’s immune
system attacks the donated graft and begins to destroying
it.
• Each person will have their own specific set of HLA
proteins that the immune system will have learned not to
attack them.
• The more genetically compatible of HLA genes between donor
and the recipient that can reduce possibility of rejection.
• The immune response is usually triggered by recognizing
of the donor’s HLA proteins as foreign antigens.
Clinical stages of rejection:
• There are three stages:
• Hyperacute rejection
• This occurs within minutes or hours after a transplantation.
• It is caused by the presence of preexisting antibodies in the
recipient, that match the foreign antigens of the donor.
• These antibodies generated as a result of previous blood
transfusions.
• The antibodies bind with cells in the blood vessels of the
graft, activates complement, with subsequent aggregation
of neutrophils and platelets, resulting in endothelial cells
damage and thrombosis, which will lead to ischemia and
graft necrosis.
Acute rejection
• This occurs within the first 6 months after transplantation.
• Acute rejection is caused by the antibodies, macrophages
and CD8+ T cells following the detection of non-self
antigens in the donated graft.
• If diagnosed early enough, acute rejection can be treated by
suppressing the immune system.
Chronic rejection
• This develops within months to years after transplantation.
• It is the major cause of long-term graft loss
• T cells reactive with alloantigen produce cytokines that
induce endothelial and smooth muscle cells proliferation
leading to vessel blockage and thrombosis
• The main pathologic finding in grafts undergoing chronic
rejection is atherosclerosis of the vascular endothelium.
• There is no cure for chronic rejection other than removal of
the graft.
What are antigens that could mediate graft rejection?
1. Major histocompatibility complex (MHC class I and
Class II).
2. Minor histocompatibility antigens (also known as H
antigens, which is peptides other than MHC proteins
such as surface protein or enzymes).
Graft versus Host Reaction (GVHR)
 When grafted tissue has mature T cells, they will attack
host tissue leading to GVHR.
 GVHR is major problem for bone marrow transplant.
 Methods to overcome GVHR:
 Treat bone marrow to deplete T cells.
 Use autologous ( bone marrow).
Thank You

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11_Transplantation_Immunity_types_of_grafts,_mechanisms_of_graft.ppt

  • 2. Transplant immunology • Transplant immunology is the study of the immune response that occurs when an organ or tissue is moved (grafted) from one individual to another. • Transplantation is the process of moving cells, tissues or organs from one site to another or from one individual to another for the purpose of repairing damaged or diseased organs. • A major problem following transplantation is that the immune system of the recipient sees the grafted tissue as ‘foreign’ and attacks and destroys it.
  • 3. • Types of tissue graft: • Autograft –Transplantation of cells, tissues or organs between sites within the same individual e.g. skin graft. •Syngeneic graft is a transfer of tissue between genetically identical individuals, i.e., identical twins • Allograft – Transplantation of organs or tissues from a donor to receipient a non-genetically identical individual of the same species. Allografts are the most common type of transplant. • Xenograft – Transplantation of an organ or tissue between two different species. ‘Pig valves’, for example, are commonly used to replace a defective heart valve in humans.
  • 4. May take place between:  different parts of the same organism (auto-grafting)  different organisms of the same species (allo-grafting)  different species (xeno-grafting) Methods of Transplantation:
  • 5. Autografting • The transfer of self tissue from one body site to another in the same individual • Due to the genetic homology of the tissue, the immune system does not respond to it • Examples  Skin grafts  Bone marrow transplantation  Hair
  • 6. Allografting Definition: It is a graft between genetically different members of the same species (human to human). • Allografts are usually rejected unless the recipient is given immunosuppressive drugs • The severity and rapidity of the rejection will depending on the degree of the differences between the donor and the recipient at the MHC loci.
  • 7. Xenografting Definition: Xenotransplantation – the transfer of tissue from one species to another (animal tissue in humans) • It is always rejected by an immunocompetent recipient. • Still under trials. • Xenotransplantation of whole organs is not currently viable. • Pig valves’, for example, are commonly used to repair or replace a defective heart valve in humans
  • 8. Graft Rejection • Graft rejection occurs when the recipient’s immune system attacks the donated graft and begins to destroying it. • Each person will have their own specific set of HLA proteins that the immune system will have learned not to attack them. • The more genetically compatible of HLA genes between donor and the recipient that can reduce possibility of rejection. • The immune response is usually triggered by recognizing of the donor’s HLA proteins as foreign antigens.
  • 9. Clinical stages of rejection: • There are three stages: • Hyperacute rejection • This occurs within minutes or hours after a transplantation. • It is caused by the presence of preexisting antibodies in the recipient, that match the foreign antigens of the donor. • These antibodies generated as a result of previous blood transfusions. • The antibodies bind with cells in the blood vessels of the graft, activates complement, with subsequent aggregation of neutrophils and platelets, resulting in endothelial cells damage and thrombosis, which will lead to ischemia and graft necrosis.
  • 10.
  • 11. Acute rejection • This occurs within the first 6 months after transplantation. • Acute rejection is caused by the antibodies, macrophages and CD8+ T cells following the detection of non-self antigens in the donated graft. • If diagnosed early enough, acute rejection can be treated by suppressing the immune system.
  • 12. Chronic rejection • This develops within months to years after transplantation. • It is the major cause of long-term graft loss • T cells reactive with alloantigen produce cytokines that induce endothelial and smooth muscle cells proliferation leading to vessel blockage and thrombosis • The main pathologic finding in grafts undergoing chronic rejection is atherosclerosis of the vascular endothelium. • There is no cure for chronic rejection other than removal of the graft.
  • 13. What are antigens that could mediate graft rejection? 1. Major histocompatibility complex (MHC class I and Class II). 2. Minor histocompatibility antigens (also known as H antigens, which is peptides other than MHC proteins such as surface protein or enzymes).
  • 14. Graft versus Host Reaction (GVHR)  When grafted tissue has mature T cells, they will attack host tissue leading to GVHR.  GVHR is major problem for bone marrow transplant.  Methods to overcome GVHR:  Treat bone marrow to deplete T cells.  Use autologous ( bone marrow). Thank You