Transplant Immunopathology Flashcards
Class 1 general
A,B,C nucleated cells
Class 2 general
DR, DP, DQ APCs
T vs B HLA markers
T - only class 1 B - both
Inheritance of HLA antigens
25% chance that a brother or sister has a perfect match
Low res HLA typing
Used for solid organ
Serological equivalent
High res HLA typing
Allele level
Needed for stem cell
Serological typing def
What is expressed on the actual cell surface is tested
HLA antibody formation
Pregnancy - more pregnancy = better chance
Blood transfusions - use LRBCs in order to decrease risk
Prvious transplant - 90% within two weeks of allograft failure (more likely for HLA-DP antibodies)…cut off immunosuppression then better chance of prudcing ABS
HLA antibody screen process
Patient serum tested against a bunch of HLA antigens coupled to beads…specificities determined and listed
cPRA
Panel reactive antibodies….greater value means less probanbility of successful match
COld ischemic time
Longer that organ goes without oxygen and blood flow, greater chance it won;t work
MFI
Mean fluorescnece intensity…higher value means more antibodies and more concern
Virtual Crossmatch
Compare on paper
Look at donor HLAs and antibodies in recipient
Corssmatch
Detects preformed donor specific HLA antibodies in recipient
Utilize donor lymphocytes and recipient serum
Minimizes risk of hyperacute rejection
AHG-CDC crossmatch
Take lymphos from donor and separate into B and T…add patient serum and enhancing agent…use complement…if cell is dyed then determines if cell isdamaged…if damaged then incompatible
Flow cytometry crossmatch
Take lymphos from donor…add antibodies (1 to T and 1 to B)…add patient serum…add flueorescent anti0IgG antibody that sticks to antibodies and can see if shift vs. negative control
Problem with crossmatch
Takes a few hours…okay for kidneys but not ideal for heart transplant
Direct pathway T cell activation
Donor APCs will find way into recipient will find way into circulation…stimulates recipient helper T cells to amount response
Indirect pathway T cell activation
INjured tissue cells are processed by recipient APCS and then presented to helper T cells
Immunosuppressive agents
Cyclosporine A or tacrolimus (calcineurin inhibitor) used with mycophenolate and steroids
Predipose to infections and neoplasms
Infections most common
In first 6 months post transplant
Neoplasms
Skin (Basal cell carcinoma or squamous cell carcinoma)
Viral (cervical squamous cell carcinoma from HPV, Post-transplant lymphproliferative disoder from EBV, Kaposi’s sarcoma from HHV 8)
Types of rejection
Hyperacute - AB mediation…secs to min
Acute - Cell or AB mediated…weeks to months or anytime with nonadherence
Chronic - multifactorail…months to years
Graft vs. host dz - cell mediated in stem cell trasnplant s
Hyperacute rejection xenotransplantation
We have naturally occurring antiboides to animal HLAs so rapidly attack
