W12.2 Flashcards
type of rejection for HSC transplant
GVHD
HSC transplant is used for
Hematologic malignancies, immunodeficiencies, bone marrow failure
Steps of HSC transplant
- For hematologic malignancies, immunodeficiencies, bone marrow failure
- Step 1. Wipe out prior immune system
- Step 2. Replace with donor bone marrow which gives rise to new blood cells including new (foreign) immune system
GVHD
situation, Neg effect, occurance
- Donor mature T/NK cells may be present in bone marrow
- Negative effect: Foreign immune system can attack the entire host body
- Occurs first 100 days post-infusion and affects skin, GI tract, liver
H. stem cells (transplantation antigen)
???
GVHD
positive effects
- GVHD can be harnessed in HSC transplants for leukemia treatment
- Graft-vs-leukemia effect helps eliminate residual recipient cancer hematopoietic cells
- T cells or NK cells mediate it
Ways to improve transplant success
(Histocompatibility Lab Diagnostics)
- HLA typing
- Pre-formed anti-HLA antibody screening
- Recipient Abs to HLA Ags
HLA typing
phenotypic or genotypic definition of the HLA antigens or genes in a transplant candidate and donor
Pre-formed anti-HLA antibody screening
detecting pre-formed Abs in recipient that may cause hyperacute rejection
CDC test
Complement-dependent cytotoxicity (CDC) test
- Classic procedure
- Requires defined antisera or mAbs to HLA antigens
- Limitations: viable Lymph. needed, antisera variations, limited resolution
HLA genotyping
- Molecular method
- Amplification of gene by polymerase chain reaction (PCR) followed by analysis of DNA sequence
- overcomes CDC limitations
Recipient Abs to HLA Ags
if Abs to donor present, that donor not further considered
Recipient ABs to HLA Ags : CDC
- panels of lymphocytes with defined HLA phenotypes are incubated with the patient’s serum
- Percent panel reactive antibody (%PRA): % lymphocytes in the panel (out of 30–60) killed by the patient’s serum
Recipient ABs to HLA Ags : ELISA
- substitute for CDC
- HLA-coated ELISA plates
Recipient ABs to HLA Ags : Flow Cytometry
- Antibody in patient serum can be incubated with latex beads that are coated with HLA antigens, either from a single donor or a single purified HLA protein
- Patient serum is incubated with the beads, and bound antibody is detected by adding a FITC-labeled anti- IgG reagent
- Most sensitive assay