Transplant Flashcards
2 things to check for transplant
HLA matching
- close matching for less alloreactivity - successful engraftment
- but not too close loses GvL effect
ABO incompatibility
HLA and Mendelian genetics
- genetic probability
Class I and Class II alleles inherit as a block
- Haplotype, no crossing over
Siblings w 100% match is 1/4
50% is 1/2
0% match is 1/4
How do T Cells alloreact to Donor cells?
How do B Cells alloreact to Donor cells?
Note positive selection of T cells to self MHC
- is bind weakly; but to antigen complex strongly
- hence if foreign MHC is close to self, less reactivity //
Our Host T cell
- Donor Antigen
- Donor MHC – this resembles self-MHC enough to bind; not eliminated by negative selection
- even self-MHC restricted T cells recognizes allogenic foreign MHC and foreign peptide complex;
- BUT more closely resemble, less alloreactivity;
B cells
- preformed or forms AB against foreign HLA, ABO incompatibility
SOT Rejections
- Hyperacute
- Acute
- Chronic
- time, mechanism
Hyper - minutes
- preformed AB
- endothelial cells - thrombosis, ischemic necrosis
- AB mechanisms: opsonization, CDCT (complement), ADCC (NKC)
Acute - days weeks
- host T cells; activated by DONOR APC (dendritic cells)
- Donor dendritic cells mature through DAMPs;
- CD8 attack
Chronic - months, years
- host T cells, activated by host PAPCs
- graft vessel narrowing through inflammation, fibrosis
whats indirect allorecognition
recipient, host APCs activate host T cells
- seen in chronic rejection
The main difference between indirect and direct alloantigen recognition stems from the origin of the macrophages (type of APC). In direct alloantigen recognition, the involved dendritic cells are donor derived. In indirect alloantigen recognition, the dendritic cells (APCs) involved are recipient APCs.
HSCT
- first step on Px? Cx?
- whats the mechanism of donated HSC for T cell maturation?
First step
- ablate bone marrow; Cx of immune reconsitution - vulnerable to infections!!!
- donated T Cell precursor will then go to thymus
- positive, neg selection using HOST peptides, HOST, APCs - restricted to host MHCs;
Whats the diff between HSCT and SOT
HSCT contains donor T cells, immune function to fight us; (more than SOT)
2 mechanisms of HSCT problems
Graft contains HSC + Donot T Cells
GvH (GvL also)
- Graft w high T cells
- using our host APCs, to activate Donor T Cells
- attack host, attack leukemia
HvG
- Graft w low T Cells
- T Cell, B Cells, ABs;
- Graft rejection
When do we give T cell replete HSCT
- what to take note of
Patient w high risk of cancer relapse
- need make sure alloreactivity
- hence HLA should not match too closely
If less than optimal HSC available
- give more T cells to kill off remaining host T cells
- block HvG transplant rejection
- increase success of engraftment
When do we give T cell deplete HSCT
To decrease chance of GvH disease
- Child w SCID, px few functional T cells, HvG risk is low; give T cell deplete to drop GvH risk
Why do we not give completely T cell deplete HSCT
Host T cells can kill off HSC
- HvG disease - rejection
