Transplant immunology Flashcards
what is HLA and where is it found
Human Leukocyte Antigen
- same as MHC
- key to self-discrimination
where are 2 classes found
1 - most somatic cells
2 - B-cell, APCs
where do we get our HLA from
one haplotype from each parent (co-dominant)
how many important HLA are there
8 loci x 2 alleles = 16 alleles - there are many others too
what does a 0/16 mismatch mean
close, but not perfect since others exist
what is importance of mismatch
predict survival
0 - very good
less difference between 1and2and3 etc
what is presently more important than HLA mismatch
presence of HLA antibodies to that HLA
3 ways one might have anti-HLA ABs
- preg.
- blood transfusion
- organ transplant
what is crossmatch test
assessment of HLA ABs in serum before transplant
what is complement dep. cytotoxitiy (CDC) crossmatch test
- give recipient serum with AB
- Ab binds HLA
- antibody fixes complement
- MAC formed and get holes
- give dye and dye enters in
- This is POSTIVE test (bad)
what happens in tranplant with pos. CDC test
hyperacute rejection - immediate loss from anitbody that is there
what is flow cytometry crossmatch test
more sens and spec.
- donor cell and recipient serum
- give fluresent tagged antiHLA AB AB (meta)
- coulter counter
what is most sensitive test
detection of HLA AB with beads coated with specific HLA antigens
- then use same method
what happens if CDC neg, but other tests positive
acute antibody mediated rejection
- 7 days post- transplant
- activates memory cells
what is importance of crossmatch test
- pos. CDC is ABSOLUTE contrainidcaiotn
2. may still reject even if neg.
what is panel reactive antibody (PRA) test
uses bead method to test a wide variety of different HLA
what is result of PRA test
get virtual match which gives percent of match to all HLA within that type
what is evidence between PRA and crossmatching
contrary reults
what can happen in transplant even with no DSA
donor MHC presented to recipient T-cells - first step in activation
3 signal model of Tcell activation
- antigen specific TCR and MHC on APC
- co-stim of CD28 on TC and CD80 on APC
- T cell releases IL-2, which bind to CD25 and get mTOR and cell proliferation
result of 3 signal model
produce many effector T-cells that eventually activate B-cells with graft AB
what happen in acute rejection
activate T-cells enter graft
- release cytokines - inflamm
- direct killing of cells epxressing forreign HLA
what do immunosuprresive drugs do (2)
- block various pathways in the T-cell activation
2. Tcell depletion
what are effects of T-cell depletion
- prevents acute rej.
- increase infection risk
- increased malignancy
- no prevention of humoral rejection
what is antibody mediated (humoral) rejection
AB s bind HLA
- activates complement to kill
what happens if knock out T and B cells
can still get rejection from monocytes
what is tolerance
durable state of antigen-specific unresponsiveness, induced by exposure to antigen in a patient who is otherwise immuno-competent
what is mixed chimerism
mixed population of donor and recipient T and B cells, so the donor supresses the host cells
