Transplant Flashcards
What is a transplant?
replacement of tissues/organs undergone irreversible pathological process which threatens patients life or hampers QOL
Transplanted organs
- lungs
- heart
- kidneys
- pancreas
- uterus
- liver
Transplanted tissues
skin
nerves
bone marrow
cornea
autograft
eg skin graft
isograft
eg identical twin
can have different HLA
allograft
eg sister - not genetically identical
xenograft
eg pig heart valves
What chromosome is histocompatibility on?
chromosome 6
HLA class 1
HLA - A,B,C
all nucleated cells
Tc
HLA class 2
HLA-DR
only APC
CD4, Th
most important in rejection
What % of transplant recipients have HLA identical donor?
30%
Privileged sites
blood flow = immunity exposed
no immunosuppression, no sensitisation etc
When does graft rejection occur?
transplant tissue is rejected by recipients immune system which destroys transplanted tissue
Graft rejection causes
ABO or HLA incompatible
sensitisation
failed immunosuppression
infections/enviro triggers
Immediate rejection
in minutes, HLA-ABO incompatible
complement activation
inflammation and thrombosis
3 phases of sensitisation in acute rejection
recognition - alloantigens
APC reaction - via MHC
co-stimulation via CD28,CD40
When does acute rejection occur?
first 6 months
Infiltrate in acute rejection
Tc, B cells, NK, macrophages
Treatment of rejection
CCS
anti thymocyte globulin
plasma exchange
Other complications of transplant
infection
bleeding
malignancy - melanoma, lymphoma
recurrence of original disease
Preventing graft rejection
ABO matching
tissue typing - class 1+2 HLA
prophylactic immunosuppression
Immunosuppression used
CCS - prednisolone
calcineurin inhibitors eg tacrolimus
anti proliferatives
What does graft versus host disease usually occur in?
bone marrow transplant
triad for graft vs host disease
immunocompetent cells in graft
defective recipient immunity
HLA differences
Preventing graft vs host disease
donor/recipient matching
donor marrow T cell depletion
Types of donors
living - related/unrelated, altruistic
dead - DBD,DCD
What happens in unmodified xenografts?
hyperacute rejection
unmodified xenografts - immunological
natural IgM human anti-swine ab –> graft endothelial galactose residues