HLA Flashcards
What is Human Leukocyte antigen testing
(3)
A specialised branch or division of immunology for histocompatibility testing
It supports specialties in transplantation, transfusion and immunogenetics
It was observed by Jean Dausset that patients whose sera contained leukoagglutinins had received more blood transfusion than other patients
What is the HLA genetic region
(3)
A series of closely linked genes that determine surface antigens or receptors responsible for the recognition and elimination of foreign tissues
It is also called the major histocompatibility complex (MHC)
The HLA complex contains an estimated 35 to 40 genes
How many classes of MHC are there
3 classes
MHC class I, II, III
What are the three loci of class III
DP
DQ
DR
What are the three loci of class I
A
B
C
What are some applications of HLA testing?
Hamatopoietic progenitor cell transplants
Solid-organ transplants
Platelet selection for refractory patients
Disease association e.g. DQ2 in Coeliac disease
Optimize certain drug therapy regimens e.g. for HIV treatment
What did we used to use HLA testing mainly for?
Paternity
Forensics
When would it be important to determine HLA antigen composition
(3)
It must be evaluated in prospective donor-recipient pairs before organ transplantation and in candidates for platelet therapy refractory to random donor platelets
Pre-sensitisation to HLA antigens may cause rapid rejection of transplanted tissue or poor platelet survival following transfusion
HLA-antigen testing is also used in disease correlation, paternity testing and anthropologic studies
How is HLA expressed
Two codominant alleles for each locus
Write about the two codominant alleles for each locus
The physical linkage of the HLA genes results in all of the genes on a single chromosome typically being inherited together
The entire set of A, B, C, DR, DQ and DP genes located on one chromosome is called a haplotype, usually inherited as a unit
Genetic crossovers and recombination in the HLA region are uncommon (less than 1%)
The HLA genotype represents the association of the alleles on the two chromosomes as determined by family studies
What is haplotype
This refers to the allelic makeup of a single chromosome
Write about linkage disequilibrium
(2)
An observed value of the joint frequency of codominant alleles that is significantly different from the expected frequency (the product of the individual allele frequencies)
Disequilibrium between the B and DR loci alleles may account for problems in correlating B locus serotyping with allograft survival and disease associations with clinical significance for allograft survival
What are HLA gene products
Globular glycoproteins, composed of two noncovalently linked chains
Class I molecules (HLA-A, HLA-B, HLA-C)
Class II molecules (HLA-DR, HLA-DQ, HLA-DP)
Where are class I molecules
Present on all nucleated cells, dendritic cells and platelets
Where are class II molecules found
Present only on B lymphocytes, activated T lymphocytes, macrophages, monocytes and endothelial cells