Transplant Immunology Flashcards
Define the following:
- Transplantation
- Graft
- Donor
- Recipent
- Allo as in allograft
The transfer (engraftment) of human cells, tissues or organs from a donor to a recipient with the aim of restoring function(s) in the body (WHO)
Graft - the transplanted tissue
Donor - the source of the graft
Recipent - individual receiving the transplant
Allo - from the genetically different member of the same species
Class 1 (HLA-A, -B and -C) gene products expressed on all cells and present antigenic peptides to CD8 T cells
Class II (HLA-DR, -DP and -DQ) expressed on APCs and present antigen to CD4 T cells
Class 1 (HLA-A, -B and -C) gene products expressed on all cells and present antigenic peptides to CD8 T cells
Class II (HLA-DR, -DP and -DQ) expressed on APCs and present antigen to CD4 T cells
3 stages?
Hyperacute - minutes to hours
Acute - Cellular (T-cell mediated) +Humeral (antibody production requiring T cella and B cell function) - days to weeks
Chronic - months - yrs
Hyperactive Rejection:
What causes it?
Why is it so rare now?
Rapid extensive thrombosis and graft infarction!
Pre-existing anti-donor antibodies in recipient (previous pregnancy, transfusion, transplantation etc.)
Targets are mainly blood group antigens and MHC molecules
Now very rare due to advances in screening and cross-matching
Acute Rejection:
What causes this
CD8 cytotoxic T cells - what do they do?
CD4 helper effector cells - what do they do?
How does it present? - 2
How is it diagnosed? - *****
Leading to a cell-mediated response
Key step is recognition of donor antigens by recipient T cells
Infiltrating the graft
- Recognise foreign MCH class 1 molecules on donor cells
- Kill the graft cells, causing tissue damage
Cytokine release
Recruitment of neutrophils and macrophages
Tissue damage, vascular compromise, ischaemia
======
Acute deterioration of graft function
Pain in region of graft and graft oedema
Biopsy
Chronic Rejection:
> 6 months
What happens to the blood vessels?
Also get FIBROSIS!
Both cellular and antibody-mediated!
Transplant vasculopathy - accelerated arteriosclerosis
Prevention:
What 3 tests need to be done?
When is it started?
What is the classical triple therapy for immunosuppression?
Combination treatment:
- Steroids
- Calcineurin inhibitor - ciclosporin
ETC.
Cross matching
ABO blood group compatibility
Histocompatibility (HLA matching)
Induction at time of transplant
(1) Corticosteroid
(2) Calcineurin inhibitor (tacrolimus or ciclosporin)
(3) Antiproliferative agent
- Azathioprine
- Mycophenolate mofetil (MMF)
- Sirolimus (rapamycin)
Treatment of Rejection:
How would you treat cellular (T-cell mediated) rejection?
Chronic rejection - manage complications
Treated with INCREASED immunosuppression
Graft Versus Host Disease:
How does this work?
What sort of curative treatment increases the risk of this?
What are the 3 stages of the mechanism? - try but can just read
It can be acute or chronic.
Acute:
- What 3 parts of the body does it affect?
Chronic:
- Variety of organ sites
Graft contains donor T cells, to which the recipient is foreign
The graft mounts an immune response against the host (to be expected
Allogeneic haematopoietic stem cell transplantation (HSCT)
(1) Activation of host APCs
(2) Donor T cell activation
(3) Cellular and inflammatory effector stage
Skin
Liver
Gut
Acute GvHD:
What happens to the skin? - 3
What happens to the liver? - 2
Gut - 4
Painful or pruritic erythematous macules
Confluent erythema, erythroderma
Subepidermal bullae, vesicles, desquamation
Deranged LFTs
Jaundice
Abdo pain
Diarrhoea
GI bleeding
Ileus obstruction
How is GvHD diagnosed?
Prevention:
Main way this is done?
What else is done? - 2
Treatment - Topical/IV Steroids
BIOPSY of skin, liver and gut
Depletion of T cells from donor graft
Donor selection (choose good match) Drugs to suppress donor T cells – same ones used to prevent transplant rejection steroids, ciclosporin, MMF
