Download Immunology_lecture13Transplantation

TRANSPLANTATION
&
tissue rejection
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
Types of transplants
1.Autograft
• Transplant of tissue to the same person.
e.g. skin, vein, stem cells
2.Allograft:
• Transplant of an organ or tissue between two genetically nonidentical 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
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:
I. Major histocompatibility antigens (MHC molecules)
II. Minor histocompatibility antigens
III. Other alloantigens
I. 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
II. Minor histocompatibility antigens
• Also cause grafts rejection, but slow and weak
III. Other alloantigens
•
•
ABO blood group antigens
Some tissue specific antigens:
– Skin, kidney, heart, pancreas ,liver
– VEC (vascular endothelial cell) antigens
Mechanism of allograft rejection
1. Cell-mediated Immunity
2. Humoral Immunity
3. Role of NK cells
Cell-mediated Immunity
• 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
Humoral immunity
• Important role in hyperacute rejection
- Complements activation
- ADCC
- Opsonization
Role of NK cells
• mediators secreted by activated Th cells can promote
NK activation
Classification of Allograft Rejection
1. Host versus graft reaction (HVGR)
Conventional organ transplantation
2. Graft versus host reaction (GVHR)
Bone marrow transplantation
Host versus graft reaction (HVGR)
1. Hyperacute rejection
2. Acute rejection
3. Chronic rejection
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
Acute rejection
 Occurs within days to 2 weeks after transplantation, 8090% 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
o Delayed hypersensitivity mediated by CD4+Th1
o Killing of graft cells by CD8+Tc
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
Graft versus host reaction (GVHR)
• 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.
1. Acute 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
Prevention and Therapy of Allograft
Rejection
1. 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)
2. Immunosuppressive Therapy
• Corticosteroids: block the synthesis and secretion of cytokines
• Azathioprine, Cyclophosphamide: block the proliferation of
lymphocytes.