Immunology 5 - Transplantation Flashcards
Average half life of a donated kidney
9-14 years (12)
The most relevant protein variations in clinical transplantation are…
ABO blood group
HLA
Which chromosome is HLA coded on?
Chromosome 6
The two major forms/components of rejection
T-cell mediated and antibody-mediated rejection
3 phases ofimmune response to transplanted graft
Phase 1 = recognition of foreign antigens
phase 2 = activation of antigen-specific T lymphocytes
Phase 3 = effector phase of graft rejection
In transplant, which HLA alleles are most important to match?
DR > B > A
What is a major determinant of the risk of rejection
The number of HLA mismatches
Number of alleles shared between parent: child and siblings
Parent to child: 50% alleles shared
Siblings: 25-50%
Phase 1 of T-cell mediated rejection
1) Presentation of foreign HLA antigens in MHC by APCs (both DONOR - direct and HOST - indirect) - aPC:TCR reaction
2) Co-stimulation
3) Amplification and activation through cytokine release
These actions occur in the lymph nodes
Phase 2 of T-cell mediated rejection (actions of activated T cells)
Proliferation Production of cytokines (IL-2 important) Provide help to CD8+ T Cells provide help for antibody production recruit phagocytic cells
Phase 3 (effector phase) of T-cell rejection
The T cells will tether, roll and arrest on the endothelial cell surface
THey will then transmigrate through the interstitium and start attacking the TUBULAR EPITHELIUM
Effect of cytotoxic T cells inside the transplanted organ
Granzyme b, perforin, Fas ligand
Histological features of T cell mediated rejection
Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubulitis
(can also get arteritis if the inflammatory cells attack the blood vessels)
A fail in graft function is not always due to rejection, what else could it be caused by?
Immunosuppressants given post transplant can be nephrotoxic, just need to adjust dose
Which type of recognition in acute rejection and chronic rejection, respsectively
Acute: direct (donor APC presenting antigen to recipient T cells)
Chronic: indirect (Recipient APC presenting antigen to recipient T cells)
Cardinal feature of antibody mediated rejection
CAPILLARITIS = inflammatory cells in the capillaries of the kidneys
Phase 3 - effector phase of antibody mediated rejection
Antibodies bind to graft endothelium
Are anti-HLA anitbodies naturally occuring?
No
How can anti-HLA antibodies be formed?
Pre-formed: pregnancy, transplant, transfusion
Post-formed
What does antibody mediated rejection eventually result in?
Graft fibrosis
How can you tell if graft is being rejected?
Raising creatinine and biopsy
Methods to prevent graft rejection
HLA typing via PCR DNA sequencing
Screening for anti-HLA antibodies before, during and after transplant
3 assays to screen for anti-HLA antibodies
Cytotoxic assays (cdc) Flow cytometry (Facs) Solid phase assays (luminex - series of beads containing all the possible HLA epitopes)
There are 3 signals to activate T cells and they can all be targeted as immunosuppresion
APC MHC to TCR
APC CD80/86 to T cell CD28 (Costimulation)
CYtokines IL-2 to T cell CD25
