HLA, HSCT, Solid Organ Flashcards

1
Q

Genes for HLA’s are on chromosome

A

6

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2
Q

What is the most polymorphic loci known in man

A

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

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3
Q

What is the HLAs function in the immune system

A

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

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4
Q

HLA Class 1

A

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

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5
Q

Expression of HLA Class 1 prevents what?

A

Destruction by natural killer cells

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6
Q

Where do HLA class 1 reside

A

On most nucleated cells and platelets.

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7
Q

HLA Class II

A

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

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8
Q

HLA class III

A

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

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9
Q

Public Antigens

A

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.

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10
Q

CREG

A

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)

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11
Q

HLA inhertiance

A

usually inherited as a haplotype

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12
Q

Finding an HLA matching sibling

A

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

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13
Q

Haplotype Match

A

sibling that inherited same haplotype from ONE parent

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14
Q

Genotype HLA match

A

sibling that inherited same genotype from BOTH parents

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15
Q

Linkage disequilibrium

A

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.

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16
Q

European example of HLA linkage disequilibrium

A

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

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17
Q

Recombination/Crossover

A

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

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18
Q

Microlymphocytotoxicity test

A

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

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19
Q

HLA detection Molecular based

A

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

20
Q

isograft/syngraft

A

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

21
Q

Allograft

A

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

22
Q

xenograft

A

from donor and recipient of different species

23
Q

hyperacute rejection

A

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

24
Q

acute rejection

A

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

25
Q

chronic rejection

A

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

26
Q

Flow Cytometry in HLA typing is used for:

A
  1. HLA typing 2. HLA antibody ID 3. HLA crossmatching most common in transplant patient/donor
27
Q

Mixed lymphocyte culture what it is

A

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

28
Q

Mixed lymphocyte culture how it’s performed

A

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

29
Q

PRA

A

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

30
Q

Single antigen bead assay

A

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

31
Q

Cyototoxic crossmatch

A

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

32
Q

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

A

It is more sensitive and it discriminates IgG vs IgM

33
Q

Positive cytotoxic crossmatch results indicate:

A

contraindication for transplant

34
Q

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

A

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

35
Q

HLA match classifications/codes

A

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

36
Q

Solid organ transplants- priorities in compatibility per organ

A

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

37
Q

birdshot retinopathy HLA correlation

A

A29

38
Q

Type 1 diabetes correlation

A

DQ3

39
Q
Autoimmune disorders/ disease due to molecular mimicry: 
1Rubella
2HTLV1-
3Herpes- 
4EBV- 
5Sterp- 
6Mycobacteria-
7H1N1 Flu-
A

1 Type 1 Diabetes

  1. Associated myelopathy
  2. Stromal Keratitis
  3. Multiple sclerosis, lupus and parkinson’s
  4. rheumatoid myocarditis
  5. bilary cirrhosis
  6. narcolepsy
40
Q

Ankylosing Sponylitis correlation

A

HLA B27, 90% gene related predominantly male

41
Q

Steven Jonson’s syndrome hyperreactivity ***

A

Allopumol Carbamazapen

42
Q

G in allele nomenclature

A

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

43
Q

P in allele nomenclature

A

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

44
Q

Stem Cell donor/recipient match

A

3/6 match or Haplomatched donor

45
Q

Choloroquine diphosphate effect on HLA antigens

A

removes 80% of HLA antigens