HLA System Flashcards
Locus of genes that encode for proteins on surface of cells that are responsible for regulation of the immune system in humans
Human leukocyte antigen system
Location of HLAs
All nucleated cells and solid tissue cells
Chromosome location of HLA genes
Short arm of chromosome 6
HLA gene inheritance
Codominant
MHC class I antigens
HLA-A
HLA-B
HLA-C
MHC class II antigens
HLA-DR
HLA-DQ
HLA-DP
HLA-DN
Functions of HLA antigens
Recognize self from non-self
Involved in immune response through antigenic stimuli
Coordinate cellular and humoral immunity
Solid organ transplant survival
Populations where combinations of alleles or genotypes can be found in expected proportions
Linkage equilibrium
Occurrence of some combinations of alleles or genetic markers in a population more often or less often than would be expected from random formation of haplotypes from alleles based on their frequencies
Linkage disequilibrium
HLA antigens found on platelets
HLA-A
HLA-B
Location of class I antigens
T cells
Most nucleated cells
Solid tissue
Location of class II antigens
B lymphocytes Monocytes Macrophages Dendritic cells Intestinal epithelium Early hematopoietic cells Epithelial cells Spermatozoa Activated T lymphs
Which HLA class is derived from exogenous proteins (proteins taken up by cell)
Class II
Which HLA class is derived from endogenous proteins (proteins made by the cell)
Class I
HLA class that interacts with T lymph’s that are CD8 positive
Class I
HLA class that interacts with T lymph’s that are CD4 positive
Class II
HLA class important for host defense against malignancy transformation and viral pathogens
Class I
HLA class that secretes immunostimulatory cytokines, important for antibody production
Class II
Testing for HLA class I molecules done by:
Microcytotoxicity testing
Sequence-specific primers
Testing for HLA class II molecules done by:
Mixed lymphocyte culture
PCR
Sequence-specific primers
HLA inheritance in which individuals share a common haplotype
Haploidentical
HLA inheritance in which individuals share no common haplotype
Haplodistinct
HLA inheritance in which individuals have exact or full-house match
HLA identical
Possibility that 2 siblings will be HLA identical
25%
Cause of absence of HLA antigens
Homozygosity at particular locus and/or to a null allele
Occurs when chromosome segments which contain genetically linked material are switched between the 2 chromosomes that are present during gametogenesis or meiosis
Crossing over
Originally identified as RBC antigens but now determined to be soluble antigens associated with plasma lipoproteins that readily absorb to RBC surfaces
Bg antigens
Bga = HLA __
HLA-B7
Bgb = HLA ___
HLA-B17
Bgc = HLA___
HLA-A28
What do Bg antibodies react with?
HLA remnants on mature red cell membrane
Measure corresponding to increased frequency a certain disease occurs when individuals have a certain HLA type when compared to individuals who do not have the certain HLA type
Relative risk
Celiac disease associated with HLA ___
DQ2
Ankylosing spondylitis associated with HLA___
B27
Narcolepsy associated with HLA___
DQ6
Chronic active hepatitis associated with HLA___
DR3
Type I diabetes associated with HLA___
DQ8
Multiple sclerosis associated with HLA___
DR15, DQ6
Rheumatoid arthritis associated with HLA___
DR4
Graves’ disease associated with HLA___
DR17
Lupus associated with HLA___
DR3
Hereditary C2 deficiency associated with HLA___
A10, B18
HLA antigens tested for transplant
A, B, C, DR, DQ, DP
Optimal allele-level match important for which HLA antigens
A, B, C, DR
Best choice of donors for HPC transplant
HLA-identical siblings,followed by mismatched donors and umbilical cord HPCs
Collective term for HLA antigen groups that have cross-reactivity
Cross-reactive group (CREG)
ABO and/or HLA match requirement for heart transplant
ABO only
ABO/HLA match requirement for cornea transplant
ABO
A, B, Dr
ABO/HLA match requirement for pancreas transplant
ABO
A, B, DR
ABO/HLA match requirement for liver transplant
ABO
DR
ABO/HLA match requirement for kidney transplant
ABO
A, B, DR
ABO/HLA match requirement for bone marrow transplant
A, B, C, DR, DQ
ABO not required
AABB standards requirement for kidney transplant candidate HLA testing
Testing for HLA antibodies once a month
“A” in HLA matching
4 antigens match
“B1U” in HLA matching
3 antigens detected in the donor, all match
“B1X” in HLA matching
3 donor antigens match, 1 cross-reactive
“B2U” in HLA matching
2 antigens detected in donor, both match
“B2UX” in HLA matching
3 antigens detected in donor, 2 match and 1 cross-reactive
“B2X” in HLA matching
2 donor antigens match, 2 cross-reactive
“C” in HLA matching
1 antigen in donor not present in recipient and not cross-reactive
“D” in HLA matching
2 antigens in donor not present in recipient and not cross-reactive
Current methods for HLA testing
Cellular assays
Molecular
Serologic
Sample requirement for HLA typing
Heparin anticoagulant
Room temp storage
Lymphocyte populations from 2 different individuals mixed and incubated with each other in tissue culture
Mixed lymphocyte culture reactions
2 populations used in mixed lymphocyte cultures
Responders and stimulators
Function of responder population in mixed lymphocyte culture reactions
Recognizes differences in HLA D loci on surface of stimulator population
Undergoes blastogenic transformation, DNA synthesis occurs and can be measured by feeding cells a radio labeled DNA precursor
Function of stimulator population in mixed lymphocyte culture reactions
Breaks foreign antigen
Pretreated with X-ray or mitomycin C to make it incapable of also responding
Testing used for HLA-A, B, C antigen typing
Microlymphocytotoxicity testing
Principle of microlymphocytotoxicity testing
Interaction of specific antibodies with HLA surface antigens on lymphocytes activates C’ and results in opaque looking cells due to cell death
Positive reaction in microlymphocytotoxicity testing
High percentage of dead cells (indicates that patient’s lymph’s have that HLA antigen corresponding to antigen in the well)
Gold standard testing for HLA typing
Sequence-based PCR
Percentage of cells that are dead after they react with cytotoxic antibodies
Panel-reactive antibody level
Methods for crossmatch and detection of HLA antibodies
Serologic microlymphocytotoxicity testing
Solid-phase/microarray
Flow cytometry
HLA antigens matched in platelet refractoriness
HLA-A and HLA-B
Reaction caused by HLA class I and II antigens in the patient against donor antibodies
TRALI