HLA, HSCT, Solid Organ

Question 1

Genes for HLA’s are on chromosome

Answer 1

6

Question 2

What is the most polymorphic loci known in man

Answer 2

HLA, chance of two unrelated individuals having identical HLA types is very low

Question 3

What is the HLAs function in the immune system

Answer 3

Antigen presentation, allorecognition-important immunological determinant for solid organ transplants

Question 4

HLA Class 1

Answer 4

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

Question 5

Expression of HLA Class 1 prevents what?

Answer 5

Destruction by natural killer cells

Question 6

Where do HLA class 1 reside

Answer 6

On most nucleated cells and platelets.

Question 7

HLA Class II

Answer 7

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

Question 8

HLA class III

Answer 8

complement proteins C2 C4 TNF can be absorbed onto RBCs, chido=C4B rogers= C4a

Question 9

Public Antigens

Answer 9

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.

Question 10

CREG

Answer 10

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)

Question 11

HLA inhertiance

Answer 11

usually inherited as a haplotype

Question 12

Finding an HLA matching sibling

Answer 12

Chance of sibling matching=25% formula = 1-(3/4)^n. n= number of siblings

Question 13

Haplotype Match

Answer 13

sibling that inherited same haplotype from ONE parent

Question 14

Genotype HLA match

Answer 14

sibling that inherited same genotype from BOTH parents

Question 15

Linkage disequilibrium

Answer 15

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.

Question 16

European example of HLA linkage disequilibrium

Answer 16

A1 = 15% B8= 10% you would think the likelihood of them being inherited together would be 1.5 but it’s actually 7.8%

Question 17

Recombination/Crossover

Answer 17

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

Question 18

Microlymphocytotoxicity test

Answer 18

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

Question 19

HLA detection Molecular based

Answer 19

small samples increased TATs, n oneed for viable cells or antigen expression, high sensitivity and specificity

Question 20

isograft/syngraft

Answer 20

graft or transplant of cells tissue or organ from one individual to another who is syngeneic (genetically identical)

Question 21

Allograft

Answer 21

graft or transpant from one individual to an MHC disparate individual- nonhistocompatible or histoincompatible due to polymorphic HLA

Question 22

xenograft

Answer 22

from donor and recipient of different species

Question 23

hyperacute rejection

Answer 23

rejection due to- preformed antibodies against a component of graft or organ

Question 24

acute rejection

Answer 24

thought to occur through T cells recognition of alloantigens on donor cells, insufficient immunosuppressants

Question 25

chronic rejection

Answer 25

occurs months or years after transplant occurs, accompanied by proliferative inflammatory lesions of small arteries, thickening of glomerular basement membrane and interstitial fibrosis

Question 26

Flow Cytometry in HLA typing is used for:

Answer 26

1. HLA typing 2. HLA antibody ID 3. HLA crossmatching most common in transplant patient/donor

Question 27

Mixed lymphocyte culture what it is

Answer 27

"cellular crossmatch" prior to transplant, takes 6 days but more sensitive than serology (microlymphotoxicity)

Question 28

Mixed lymphocyte culture how it's performed

Answer 28

lymphocytes from patient and donor cultured together. Each cell able to recognize the "foreign" HLA antigens of other-lymphocytes transform into blast cells - synthesize DNA and take up radioactive thymidine. if there is an uptake of radioactive thymidine this indicates lymphocytic activation

Question 29

PRA

Answer 29

panel reactive antibody, identifies antibody specificity and antigens to avoid from donor in future transfusions

Question 30

Single antigen bead assay

Answer 30

polysteryne beads impregnated with different concentrations of dyes, 100 unique beads can be coated with different HLA antigens,Patient plasma is added-HLA antibodies will bind to corresponding antigen on bead. PE labeled IgG added and binds to IgG that is bound to the bead, emits fluorescence- detectable each antigen=specific fluorescence

Question 31

Cyototoxic crossmatch

Answer 31

HLA anitobdy crossmatch, recipient serum and donor lymphcytes (MUST BE FRESH WITHIN 48 HOURS) this is used to prevent a hyperacute rejection

Question 32

Flow cytometry in antibody testing for HLA can be an advantage because (2)

Answer 32

It is more sensitive and it discriminates IgG vs IgM

Question 33

Positive cytotoxic crossmatch results indicate:

Answer 33

contraindication for transplant

Question 34

Bennett good speed HLA antigens (3) and problems they cause

Answer 34

Bga-B7 Bgb-8 Bgc-A28, antibodies against these may react against red cells with HLA remnants

Question 35

HLA match classifications/codes

Answer 35

A (4anitgen match this is the best) B1V-3 anitgens fourth is unknown B1X-3 antigens 4th is reactive, B2U, B2X, B2UX, C, D -in order of most compatible to least compatible

Question 36

Solid organ transplants- priorities in compatibility per organ

Answer 36

ABO compatibility is the most important. Liver HLA matching may have no effect. Hear some centers match for HLA type, Degree of HLA compatibility corresponds with graft survival

Question 37

birdshot retinopathy HLA correlation

Answer 37

A29

Question 38

Type 1 diabetes correlation

Answer 38

DQ3

Question 39

``` Autoimmune disorders/ disease due to molecular mimicry: 1Rubella 2HTLV1- 3Herpes- 4EBV- 5Sterp- 6Mycobacteria- 7H1N1 Flu- ```

Answer 39

1 Type 1 Diabetes 2. Associated myelopathy 3. Stromal Keratitis 4. Multiple sclerosis, lupus and parkinson's 5. rheumatoid myocarditis 6. bilary cirrhosis 7. narcolepsy

Question 40

Ankylosing Sponylitis correlation

Answer 40

HLA B27, 90% gene related predominantly male

Question 41

Steven Jonson's syndrome hyperreactivity ***

Answer 41

Allopumol Carbamazapen

Question 42

G in allele nomenclature

Answer 42

HLA allele that encodes for identical nucleotide in peptide binding domain. Identical DNA = G code

Question 43

P in allele nomenclature

Answer 43

HLA alleles that share identical nucleotide sequences for the EXONS encoding the peptide binding domains- Identical Protein for the peptide pinding domain =P code

Question 44

Stem Cell donor/recipient match

Answer 44

3/6 match or Haplomatched donor

Question 45

Choloroquine diphosphate effect on HLA antigens

Answer 45

removes 80% of HLA antigens