Immuno - Transplantation Flashcards
Which HLA types do we look for mismatching
HLA-A
HLA-B
HLA-DR
DR>B>A in terms of importance
A and B are on MHC I whilst DR is on MHC II
The more the mismatches, the greater chance of infection
Receiving graft from a single parent, what are maximum number of mismatches
3/6
You receive 3 HLA types from each parent so you will match with at least 3. Its possible to match with more if your parents share the same HLA types.
Maximum number of mismatches allowed is 6
Receiving grant from a sibling, what are the %age mismatches for 0, 3 and 6 mismatches
0 mismatches - 25%
3 mismatches - 50%
6 mismatches - 25%
What screening methods can be used to test donor cells against host serum?
Cytotoxicity assay - checks to see if donor cells get destroyed in presence of complement. If they do, suggests that there are anti-donor antibodies in host serum
FACS - Can look to see if serum antibody is binding to donor cells. Can be done with fluorescent anti-human IgG
Solid phase assay - does recipient serum bind to donor HLA molecules on solid beads?
What screening methods can be used to test donor cells against host serum?
HLA Typing
Screen for anti-HLA molecules
Which molecules are recognised in a transplant?
HLA types
Minor HLA
ABO
In transplant, what are the two types of recognition?
Direct - DONOR APC presenting MHC to host immune cells. Acute rejection mainly involves this - very quick response.
Indirect - HOST APC present donor antigens as normal - like a normal immune response
Types of transplant rejection
Hyperacute
Hyperacute
When host has PREFORMED antibodies vs donor HLA already which activates response and causes rejection within minutes-hrs.
Results in thrombosis and necrosis
Prevent with good HLA matching, screening for anti-HLA antibodies and IMMUNOSUPPRESSION
Types of transplant rejection
Acute
Can be cellular or antibody mediated, weeks-months
Cellular is T-cell mediated and there will be cellular infiltration on biopsy. Treat with T-cell suppression.
Ab is B-cell mediated and there will be vascultis or C4d deposition. Treat with Ab clearance and B-cell suppression
Types of transplant rejection
Chronic
Months-years
Due to many acute rejection episodes - Fibrosis and damage to blood vessel supply, leading to ischaemia and organ failure. Treat by minimising organ damage
Types of transplant rejection
GvHD
Days-weeks
Donor cells attacking host
Skin rash, bloody D+V, jaundice are classic signs.
Prevent with immunosuppression/steroids
Types of transplant rejection
Acute vascular rejection
Similar to hyperacute but takes 4-6 days.
Happens after a xenograft - graft from another species
Immunosuppression regime
Inducting agent (all anti-T cell):
OKT3/ATG (anti-CD3), anti-CD52, anti-CD25
Post transplant baseline immunosuppression:
Tacrolismus/cyclosporin
mycophenolate mofetil/azothioprine
+-steroids
Manage acute episodes of rejection:
Cell mediated: Steroids, OKT3/ATG
Ab mediated: IVIG, plasmapheresis, anti-C5, anti-CD20
Drugs
OKT3
Anti-CD3
Drugs
Anti-thymocyte globulin (ATG)
Anti-CD3
