Transplant Flashcards
1
Q
MHC and transplant
A
- there is MHC class I- HLA-A, B, C, D, E, F, G
- there is MHC class I- HLA-DM, DO, DP, DQ, DR
- some are highly polymorphic, some aren’t as much, some are harder/easier to match
2
Q
Blood Group Antigens
A
- blood in the most common transplant
- blood groups are antigens of the surface of most cells of the body. Most people have “natural” antibodies against other blood groups
- they differ by one carbohydrate
- O has anti-A, and anti-B antibodies
- A has anti-B, B has anti-A, AB- no antibodies
- also have to deal with Rh
- ABO method agglutionation
3
Q
Hyperacute rejection
A
- the most severe and immediate type
- caused by preformed antibodies
- most common is blood group antigen
- also could have pre-existing HLAs-
- antibodies against donor blood group antigens bind vascular endothelium of graft, initating an inflammatory response occlude blood vessels -> graft is engorged and purple because of hemorrhage
4
Q
Cross Match
A
- antibodies to HLA
- IgG antibodies
- from previous transplant
- a lot of blood transfusions
- women give birth
5
Q
Panel Reactive Antibody
A
- the serum of a recipient is tested against a panel of leukocytes from many individuals- how many wells do they have reaction
- detection of the presence of antibodies to HLA
- presented as percentage-0-100%, low value less likely to react
6
Q
Acute rejection
A
- T cells from recipient become reactive against the transplant
- takes to week
- stronger response to donor cells expressing MHC II- present in graft and elicit a strong immune response
- second is indirect with presentation of dead donor cell by host APCs
- most immune suppression therapies are directed towards inhibiting acute rejection
7
Q
Chronic rejection
A
- takes months or years and is primarily the result of indirect recognition of the transplant.
- it may be to MHC molecules or towards other minor transplantation antigens
- associated with the presence of antibodies to HLA-class 1 antigens in the graft which seem to act on the vasculature of the graft
8
Q
Matching HLA
A
- important
- not critical to survival
- when possible matching is done, when critical blood type matching will suffice
- 0 mismatches- 13.4 half life, 6 misses- 8.9 halflife
9
Q
Testing at transplantation
A
- Repeat ABO on donor
- HLA I and II on donor
- find match on computer net
- cross match on all positive sera from antibody screening
10
Q
Workup for transplantation- HLA I
A
- HLA Type I
- should find 6 type I antigens unless there is homozygosity
- 2A loci, 2B loci, 2C loci
11
Q
Workup for transplantation- HLA II
A
- panal reactive antibody
- mixed lymphocyte reaction
- molecular techniques
12
Q
Anti-ABC antibody testing
A
- Anti-HLA-ABC testing done monthly
- presensitization by graft, transfusion, pregnancy
- used for cross-matching against donor lymphocytes
13
Q
Corticosteroids
A
- these relatives of cortisol interfere with a transcription factor needed to turn on the genes for T cells to become activated
- knock out T cells
- prednisone and prednisolone
- decrease IL-1, 3, 4,5 CXCL8- decrease inflammation, also decrease adhesion molecules etc
14
Q
Cytotoxic drugs
A
- interfere with DNA synthesis
- interfere with the rapid cell proliferation needed for immune responses
- Azathrioprine- purine analog
15
Q
FK506 and cyclosporine
A
- natural product isolated from microbial cultures
- inhibit signaling pathway used by T cells to turn on their genes for activation, IL-2 secretion
- FK506 is known as tacrolimus, cyclosporine is Neoral
