1. TRANSPLANTATION & tissue rejection

2. Organ transplantation:
Is the moving of an organ from one body to another for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor site. Organ donors can be living or deceased
Organs that can be transplanted:
the heart, kidneys, liver, lungs, pancreas, eyes and intestine.
Tissues that can be transplanted:
bones, tendons, cornea, heart valves, veins, and skin

3. Types of transplants 1.Autograft 2.Allograft: 3.Isograft: (Syngeneic)
Transplant of tissue to the same person.
e.g. skin, vein, stem cells
2.Allograft:
Transplant of an organ or tissue between two genetically non-identical members of the same species
Most human tissue and organ transplants are allografts
3.Isograft: (Syngeneic)
A subset of allografts from a donor to a genetically identical recipient (e.g. identical twin).
Isografts don't trigger an immune response.
4.Xenograft:
A transplant of organs or tissue from one species to another
e.g. porcine heart valve transplants

4. Immunologic Basis of Allograft Rejection Grafts rejection
Is a kind of specific immune response to the organ which causes failure of the transplant
Specificity
Immune memory
Transplantation antigens:
Major histocompatibility antigens (MHC molecules)
Minor histocompatibility antigens
Other alloantigens

5. Major histocompatibility antigens (MHC molecules)
Main antigens of grafts rejection
Cause fast and strong rejection
Difference of HLA types is the main cause of human grafts rejection
Minor histocompatibility antigens
Also cause grafts rejection, but slow and weak
Other alloantigens
ABO blood group antigens
Some tissue specific antigens:
Skin, kidney, heart, pancreas ,liver
VEC (vascular endothelial cell) antigens

6. Mechanism of allograft rejection
Cell-mediated Immunity
Humoral Immunity
Role of NK cells
T cell-mediated cellular immune response against alloantigens on grafts
T cells of the recipient recognize the allogeneic MHC molecules
i.e. uptake and presentation of allogeneic donor MHC molecules by recipient APCs
activated CD4+T cells  MΦ activation and recruitment
Activated CD8+T cells  Kill the graft cells

7. Humoral immunity Role of NK cells
Important role in hyperacute rejection
Complements activation
ADCC
Opsonization
Role of NK cells
mediators secreted by activated Th cells can promote NK activation

8. Classification of Allograft Rejection
Host versus graft reaction (HVGR)
Conventional organ transplantation
Graft versus host reaction (GVHR)
Bone marrow transplantation

9. Host versus graft reaction (HVGR)
Hyperacute rejection
Acute rejection
Chronic rejection

10. Hyperacute rejection
Occurs within minutes to hours after host blood vessels are anastomosed to graft vessels
Pathology:
Thrombotic occlusion of the graft vasculature
Ischemia, denaturation, necrosis
Mechanisms:
Antibody against ABO blood type antigen
Antibody against VEC antigen
Antibody against HLA antigen
Complement activationEndothelial cell damage
Platelets activation  Thrombosis, vascular occlusion, ischemic damage

11. Acute rejection
Occurs within days to 2 weeks after transplantation, 80-90% of cases occur within 1 month
Pathology
Acute humoral rejection:
Acute vasculitis manifested mainly by endothelial cell damage
Acute cellular rejection:
Parenchymal cell necrosis along with infiltration of lymphocytes and MΦ
Mechanisms
Vasculitis: IgG antibodies against alloantigens on endothelial cell
Parenchymal cell damage
Delayed hypersensitivity mediated by CD4+Th1
Killing of graft cells by CD8+Tc

12. Chronic rejection
Develops months or years after acute rejection reactions have subsided
Pathology
Fibrosis and vascular abnormalities with loss of graft function
Mechanisms
Not clear
Extension and results of cell necrosis in acute rejection
Chronic inflammation mediated by CD4+T cell/MΦ
Organ degeneration induced by non immune factors

13. Graft versus host reaction (GVHR)
Allogeneic bone marrow transplantation.
Rejection to host alloantigens.
Mediated by immune competent cells in bone marrow.
Graft versus host disease (GVHD)
A disease caused by GVHR, which can damage the host.
Acute GVHD
Chronic GVHD
Conditions
Enough immune competent cells in grafts.
Immunocompromised host.
Histocompatability differences between host and graft.

14. 1. Acute GVHD 2. Chronic GVHD
Endothelial cell death in the skin, liver, and gastrointestinal tract
Rash, jaundice, diarrhea, gastrointestinal hemorrhage
Mediated by mature T cells in the grafts
2. Chronic GVHD
Fibrosis and atrophy of one or more of the organs
Eventually complete dysfunction of the affected organ
Both acute and chronic GVHD are commonly treated with intense immunosuppresion

15. Prevention and Therapy of Allograft Rejection
Tissue Typing
ABO and Rh blood typing
HLA typing (HLA-A and HLA-BHLA-DR)
Screening of the recipient for anti-HLA antibodies (also called antibody screening)
Lymphocyte cross matching (also called compatibility testing)
Immunosuppressive Therapy
Corticosteroids: block the synthesis and secretion of cytokines
Azathioprine, Cyclophosphamide: block the proliferation of lymphocytes.