Immuno 7: Transplant Flashcards
What are the 2 most important protein variations that determine donor organ compatibility ? (Least likely to be rejected)
HBO blood group
HLA
Which 3 HLA isotypes are considered the most immunogenic ?
HLA-A
HLA-B
HLA-DR
How can transplanted organs cause a T-cell mediated immune response ?
If there is a mismatch in HLA molecules APC cells present foreign HLA to naive T cells in the lymph nodes
The CD4+ T cells activate Cytotoxic CD8+ T cells and macrophages
Do we have pre-formed HLA-antibodies ?
No
Unless you have previously had a transplant, received a blood transfusion or been pregnant
What could cause a hyperacute rejection of an organ transplant ?
If you already had pre formed HLA-antibodies
List 3 ways antibodies cause killing of pathogens/graft ?
1- Neutralising by binding directly to pathogen or toxin
2- Opsonising the pathogen/graft so Phagocytes can clear it
3- Binding to pathogen/graft so NK cells can recognise FC receptor of antibody and destroy the pathogen/graft
List 2 ways antibodies cause killing of graft via complement?
1- Antibody binds to HLA molecule on endothelium of the graft. The Fc region canactivate the classical complement cascade leading to formation of the membrane attack complex which ends in cell lysis
2- Antibody binds to HLA molecule on endothelium of graft. The activation of complement cascade recruits NK cells and other mononuclear cells which kill the graft cells.
How does Antibody mediated transplant rejection look different to T cell mediated transplant rejection on histology ?
Antibody mediated- Microcirculation inflammation (endothelium)
T cell mediated - Tubulointerstitial inflammation
What are the 3 main types of anti-HLA assays to screen for antibodies against the graft ?
Cytotoxicity assay- looks whether there is cell lysis between patients serum and donor antibodies if complement is added
Flowcytometry- flourescently labelled anti-human antibodies detects antibodies to the graft
Solid phase assays- uses recombinant proteins of all the HLA molecules in fluorescent beads. Looks at which bead fluoresces to see which HLA molecules are causing an immune reaction
What is the role of IL2 in T cell mediated immune response to graft ?
IL2 is a cytokine that causes autocrine and paracrine activation of T cells
List 3 immunosuppressive agents used in transplants that target T cells ?
Cyclosporin- Calcineurin inhibitor
Azathioprine- cell cycle inhibitor
Anti CD3 antibody (muromonab)- targets TCR
Daclizumab- anti-CD25 antibody
List 3 immunosuppressive agents used in transplants that target antibody mediated rejection ?
Rituximab- anti CD20 antibody
Eculizumab- Complement inhibitor
BAFF inhibitors- blocks cytokines
Explain graft vs host disease ?
1- The recipients immune system is wiped out by radiation therapy.
2- The donor stem cells set up a new immune system in the recipients bone marrow
3- The new immune system can start attacking the hosts organs because they recognise the self antigens as foreign
What is one possible benefit that can occur as a result of graft vs host disease ?
Immune response can attack tumours (graft vs tumour effect)
Which 2 drugs are commonly given for GVHD prophylaxis ?
Methotrexate
Cyclosporin
