Lecture #13 Flashcards
Graft
Transplanted tissue/ organ
Ortotopic transplantation
The graft is placed in its normal anatomical position
Heterotrophic tranplantation
The graft is placed not in its normal anatomic position
Isograft/ syngraft
The donor and the recipient are homozygotic tweens
Autograft
The donor and the recipient are the same person
Allograft
The donor and the recipient are different persons
Xenograft
The donor is an animal
Primary rejection of an allograft Ex skin allograft
10-14 days
The tissue establishes blood supply (angiogenesis) - immune cells are infiltrated - thrombosis - ischemia - necrosis
Secondary rejection of an allograft Ex skin allograft
5-6 days
The tissue already has blood supply therefore infiltration of immune cells is rapid so does thrombus - ischemia and necrosis
Critical matching criteria between donor and recipient
- Major histocompetability complex
mainly HLD-A HLA-B HLA-DR - Minor histocompetability molecules
H-Y on the Y chromosome, HA1-HA5 autosomal peptideson HSC - ABO Rh blood groups, VEC vascular endothelial cells antigen system, SK Skjelbred antigen
Liver transplantation survival rates
1y survival over 75%
5y survival 70%
Heart transplantation
We preform heart transplant only if the patient has more then 50% to die in the present year
5y survival is 80% after 5y CHD will develope
Pancreas transplantation
1y survival 72% but improves along with kidney transplantation
Cornea transplantation
60-70% acceptance
HLA matching is not prerequisite
Direct alloreactivity
- Sensitization - the donor’s APCs will go to the lymph nodes and present their self antigen to T cells
- Rejection - activated lymphocytes (all types) will reach the organ via blood circulation and attack it (humoral and cytotoxic)
ACUTE and intense
Indirect alloreactivity
- Sensitization - the recipient’s APCs will engolf antigns from the transplanted tissue and present them to T cells in the lymph nodes
- Rejection - activated lymphocytes (mainly Th1 and B cells) will reach the organ via blood circulation and produce Ab against the antigens (humoral mainly)
CHRONIC and mild
3 types of HVG reactions (in solid organs)
- Hyperacute - Preformed Ab against antigens of the donor due to previous exposure to ABO, HLA, VEC antigens
Ex: pregnancy, abortion, blood transfusion, previous organtransplantation
The mechanism of rejection is humoral (vasculitis) - Acute - Can be humoral (vasculitis) or cellular (parenchymal damage)
- Chronic - mediated by Th1 and macrophages - granuloma formation - fibrosis - loss of activitiy of the organ
How do we prevent transplantation rejection?
- Donor selection
- In vitro graft manipulation - elimination of the donor’s immunocompetent cells by steroid infusion/ tolerance induction/ anti CD28/ anti CD4/ anti MHCII…
- Immunosuppression of the recipient by anti IL2R, anti TCR, abatacept, GCS (inhibit cytokine production)
What are the conditions to development of GVHR?
- Presence of immunocompetent cells in the graft
(bone marrow, thymus, spleen, neonatal blood transfusion but also liver, lung, gut) - Impaired imune defense of the recipient
- Different HLA genes or minor histocompetability molecules
In GVHR the damage to the recipient cells is via
Apoptosis
Fas-FasL , TNF, granzymes and perforins
