HLA, HSCT, Solid Organ Flashcards
Genes for HLA’s are on chromosome
6
What is the most polymorphic loci known in man
HLA, chance of two unrelated individuals having identical HLA types is very low
What is the HLAs function in the immune system
Antigen presentation, allorecognition-important immunological determinant for solid organ transplants
HLA Class 1
A, B, and C, present peptides from within the cell, digested viral proteins, self proteins or malignant cell proteins. Attract CD8+ cytotoxic T cells lead to cell death, adaptive immune response
Expression of HLA Class 1 prevents what?
Destruction by natural killer cells
Where do HLA class 1 reside
On most nucleated cells and platelets.
HLA Class II
DR, DQ, and DP. presents peptides from outside of the cell. Phagocytosed bacteria. Stimulate CD4+ T helper cells- stimulates antibody production, b cells, cytotoxic T cells and modulate immune response. These are on Antigen Presenting Cells (B cells, Marcophages, monocytes, dendritic cells intestinal epithelium, microvascular endothelium. Mostly DR, `20% DQ and very low DP
HLA class III
complement proteins C2 C4 TNF can be absorbed onto RBCs, chido=C4B rogers= C4a
Public Antigens
Less variable portion of the HLA molecule. Bw4 and Bw6 on almost all HLA-B molecules , can be very difficult to match if someone forms an antibody to a public antigen.
CREG
Cross-reactive antigen Group. Many common epitopes, antibodies bind common epitopes. Cross reactivity in serologic testing, unable to distiguish by serologic testing alone (HLA-B15 and B16)
HLA inhertiance
usually inherited as a haplotype
Finding an HLA matching sibling
Chance of sibling matching=25% formula = 1-(3/4)^n. n= number of siblings
Haplotype Match
sibling that inherited same haplotype from ONE parent
Genotype HLA match
sibling that inherited same genotype from BOTH parents
Linkage disequilibrium
When alleles of some haplotypes ocur more frequently than would be expected on the basis of chance alone. . Potentially due to survival advantage certain haplotypes are more likely to be inherited together.
European example of HLA linkage disequilibrium
A1 = 15% B8= 10% you would think the likelihood of them being inherited together would be 1.5 but it’s actually 7.8%
Recombination/Crossover
Genes that are closely linked. rarely occurs but creates new haplotypes. 0.8% between HLAA-and HLAB. 1.5% between HLA-B and HLA-DR
Microlymphocytotoxicity test
Serologic Detection of HLA antigens. HLA antibodies on plates. Lymphocytes from patient added. T and B cells- Class 1 typing. B cells- Class 2 typing. Rabbit complement added. Antiobidy binding causes complement activatin and cell death. Dye added, intact cells exclude dye and appear refractile. Dead cells incorporate dye; HLA type defined when antibodies cause lysis of >50% of patients cells. Grade is based off of color-death