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Transplantation Immunology

Transplantation Immunology
Transplantation is the process of taking cells, tissues or organs called a graft from one individual & placing them into a different individual.
A major factor limiting the success of transplantation is the immune response of the recipient to the donor tissue.
The major molecular targets in transplant rejection are class I & class II MHC molecules & are called alloantigens.

Types of graft

Types of graft
Autologus graft (autograft), is self-tissue transferred from one body site to another in the same individual.
Syngeneic (isograft), transfer of graft between two genetically identical individuals like identical twins.
Allogeneic graft, transfer of the graft between two genetically different individuals of the same species.
Xenogeneic graft, a graft transplanted between individuals of different species.

Types of graft rejection

Hyperacute rejection
Thrombotic occlusion of the graft vasculature that begins within minutes or hours
Mediated by preexisting antibodies in the host serum that bind to the donor endothelial Ags.
It is usually mediated by IgG Abs directed against specific Ags such as foreign MHC molecules due to previous blood transfusion, transplantation or multiple pregnancies.
Activation of complement followed by platelets deposition leading to thrombosis & endothelial injury.
The grafted organ suffers irreversible ischemic damage.
No CMI .
The graft should be removed.


Types of graft rejection
Acute rejection
Occurs within 6 months of transplantation.
Process of necrotizing vasculitis & paranchymal injury mediated by T cells & Abs.
T lymphocytes play a central role ( both CD+ 4 & CD8+ T cells).

Acute rejection

CD+ 4 T cell recognize donor HLA after they are processed & presented by host APCs.
CD+4 T cells will secrete cytokines that induce DTH & stimulate production of Abs.
CD+8 cells respond to donor HLA expressed directly on donor cells resulting in lysis of the target cells in the graft.
If it is recognized and treated , the transplant will survive.

Types of graft rejection

Chronic rejection
Graft that slowly occurs within 6 months to a year after transplantation resulting in arterial occlusion as a result of the proliferation of intimal smooth muscle cells called vascular arteriopathy that lead to ischemic damage.
Caused by both antibody & cell-mediated immunity.
Chronic delayed hypersensitivity like- reaction of host T cells to donor alloantigens in the graft vessel.
May end with fibrosis of the organ.

Preparation for transplantation

ABO & Rh compatibility
HLA typing : focused on HLA-A, B & HLA-DR.
Cross matching , if a potential donor is identified, the recipient serum is tested for reactivity against the donor lymphocytes using complement- mediated lysis. A positive crossmatch is a contraindication for transplantation.
Use of immunosuppressive agents.
Prophylactic antibiotics.
Vaccination against some capsular bacteria.


Use of Immunosuppressive agents
Immunosuppression
The main approach used for prevention & management of graft rejection.
Immunosuppressive drugs is the principal treatment for graft reduction, used to kill or inhibit T lymphocytes.
Cyclosporine, is an antibiotic that is produced by a species of fungus. It acts by inhibition of T cell transcription of certain genes that encode for IL-2. This will result in blocking growth & differentiation of T cells.
FK-506 (tacrolimus) is a macrolid made by a fungus. It functions like cyclosporine.

Use of Immunosuppressive agents

Rapamycin (Sirolimus), its principal effect is to inhibit T cell proliferation.
Anti-inflammatory agents are routinely used for prevention & treatment of graft rejection , the most potent is corticosteroids. They block the synthesis & secretion of TNF & IL-1 by macrophages.
Antiproliferative drugs such as methotrexate and azathioprine.
Anti CD3 antibodies to reduce activity of T cells.
Anti-cytokine antibodies.
Antibodies that block leukocyte- endothelial adhesion molecules such as anti-ICAM-1.

Graft Versus Host Disease

Caused by reaction of grafted immunocompetent T lymphocytes against the recipient tissue.
Occurs when the host is immunocompromised & unable to reject the transplanted cells



Graft Versus Host Disease
Acute GVHD:
manifested clinically by rash, jaundice, diarrhea & GIT bleeding. It may be fatal.
Chronic GVHD
characterized by lymphadenopathy, hepatosplenomegaly with fibrosis of the grafted organ due to inflammation and destruction of the host tissue.
It can be also fatal.

GVHD

Management
Both acute and chronic are treated by intensive immunosuppressive therapy.
Prophylaxis of GVHD
Anti- CD3 Abs to inhibit T cells in the grafted tissue.
Irradiation of blood & blood products before giving to the host.




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