Mechanism of Allograft Rejection: A Comprehensive Overview, Study Guides, Projects, Research of Immunology

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Mechanism of

allograft rejection

, By

Syed Muhammad

22Q

PharmD

Transplantation:

Is the moving of a cell, tissue or organ from one body

to another for the purpose of replacing the recipient's

damaged or failing cells 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

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

Humoral immunity

• (^) Mediated by humoral antibodies
• (^) These include performed circulating antibodies
• (^) Important role in hyperacute rejection Complements activation ADCC Opsonization Role of NK cells
• (^) Mediators secreted by activated Th cells can promote

NK activation

1. Host versus graft reaction (HVGR)

Conventional organ transplantation

2. Graft versus host reaction (GVHR)

Bone marrow transplantation

Classification of Allograft Rejection

Host versus graft reaction (HVGR)

**1. Hyperacute rejection

2. Acute rejection
3. Chronic rejection**

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 o (^) Delayed hypersensitivity mediated by CD4+Th 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

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.