Immunology 3 - Transplantation Flashcards
Recall the 3 phases of immune response to a transplanted graft
- Recognition of foreign antigens
- Activation of antigen-specific lymphocytes
- Effector phase of grant rejection
What are the 2 most variant protein variants in clinical transplantation?
ABO blood group
HLA antigens
On which type of cell is HLA class I expressed?
All cells
On which type of cell is HLA class II expressed?
Antigen-presenting cells
Which part of the HLA molecule is highly variable?
Peptide binding groove in between the alpha subunits
In T cell-mediated transplant reaction, how are alloreactive T cells activated?
- Both donor and host APCs present foreign HLA in MHCs
2. Costimulatory signals
Which types of HLA fall into each class?
HLA-A, B, C = class 1 HLA-DR, DQ, DP =class 2
What are the actions of activated T cells in T cell-mediated transplant rejection?
- Proliferation
- Produce cytokines (especially IL2)
- ‘Help’ CD8+ cells
- ‘Help’ antibody production
- Recruit phagocytic cells
What test can be used to see if transplant rejection is occurring?
A biopsy - an inflammatory response will be seen
What are the key histological features of T cell-mediated transplant rejection?
Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubulitis (inflammatory cells within the tubular epithelium)
Macrophages, recruited by the T cells
Recall the 3 phases of antibody mediated rejection
- B cells recognise foreign HLA
- Proliferation and maturation of B cells with anti-HLA antibody production
- Effector phase: antibodies bind to graft ENDOTHELIUM
Recall the process of antibody-mediated rejection phase 3
Antibody binding to transplanted organ vessel endothelium –> complement activation to form MAC and monocyte/neutrophil recruitment via Fc receptor –> endothelial injury and inflammation (capillaritis)
Capillaritis is a cardinal feature of antibody-mediated rejection
What are the key histological features of antibody-mediated transplant rejection?
- Inflammatory cell infiltrate
- Capillaritis
- Immunohistochemistry shows fixation or complement fragments on endothelial cell surfaces
Describe the effector phase of T cell-mediated transplant rejection
The T cells will tether, roll and arrest on the endothelial cell surface
They will then crawl through into the interstitium and start attacking the tubular epithelium
What test is used to do HLA typing before a transplant?
PCR-DNA sequencing