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Immunohaematology I > Human Leukocyte Antigen > Flashcards

Human Leukocyte Antigen Flashcards

1
Q

What is tissue typing?

A

Detection of antigens on the surface of lymphocytes.

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2
Q

What is the HLA system?

A

Human Leukocyte Antigen system.

  • Important in compatibility testing for tissue and bone marrow transplantation
  • HLA antigens are expressed on all nucleated cells in the body
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3
Q

What HLA antigens does T and B lymphocytes carry respectively?

A 
T-cells: MHC class I antigens (A, B, C loci)
B-cells: MCH class II antigen (DR, DP, DQ loci)
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4
Q

Why can HLA antigens cause complications in patients who need repeated blood transfusions?

A

Some transfusion products contain WBCs and PTLs which express HLA Ag’s on their surfaces.

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5
Q

What are the locus classes of HLA?

A

Class I: HLA A, B, Cw

Class II: HLA D, DR, DQ, DP

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6
Q

List a few HLA antigen subtypes from each of these locus classes.

A

HLA A2, HLA B12, HLA Cw*02021, Dw1, DR1, DQw1, DPw1

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7
Q

Discuss inheritance, classes, and expression of MHC/HLA.

A

Inheritance:

  • An individual has 2 of each A, B, Cw and DR antigens, one set from each parent
  • Each set is a haplotype, so inherit 2 haplotypes

Classes:

  • Class I
    1. 2 Chains: Alpha chain w/ 3 regions, Beta-2-microglobulin chain
    2. Variations of HLA A, B, Cw types depend on Alpha 1 and 2 regions
  • Class II
    1. 2 Chains: Invariant Alpha chain w/ 2 regions and Beta chain w/ 2 regions
    2. Variations of HLA DR types depend on Beta 1 and 2 regions

Expression:

  1. HLA A, B, C: On all nucleated cells in the body
  2. HLA DR, DP, DQ: B-cells and APCs
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8
Q

What is the principle of HLA testing?

A
  1. Micro-lymphocytotoxicity testing: T-lymphocyte phenotypes
  2. Leucoagglutination: Febrile Transfusion Reactions
  3. Mixed Lymphocyte Culture (MLC) technique: D locus Ag
  4. ‘C fixation: Presence of PTL Abs and non-HLA specifics
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9
Q

What HLA antigens are tested on RBCs?

A

Bga - HLA-B7
Bgb - HLA-B17
Bgc - HLA-A28

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10
Q

What does HLA system tissue typing include?

A
  1. Detection of HLA Ags
    - By serology (lymphocytotoxicity test)
    - By DNA/Molecular techniques (PCR and qPCR)
  2. Detection of HLA Abs
  3. Cross-matching (using spleen and lymph nodes harvested samples)
  4. Blood Grouping
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11
Q

Discuss serology HLA testing for class I typing.

A

Principle: Using sodium citrated blood

Isolation: Blood is defibrinated to remove PTLs and lymphocytes are removed after blood processing on a gradient medium and centrifuged.

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12
Q

Discuss serology HLA testing for class II typing.

A

Principle: Using EDTA anticoagulated blood

Isolation: Immunomagnetic beads coated with a monoclonal Ab directed at the target Ag are used for fast reliable positive selection of B cells that contain class II Ags. Done using ‘C dependent cell lysis.

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13
Q

What is the application of HLA testing?

A
  1. Tissue transplantation
  2. Forensic Investigations
  3. Disputed Parentage
  4. Platelet Transfusions
  5. Disease Association
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14
Q

What is the role of HLA in transplantation?

A

Bone Marrow:

  • Graft survival depends on HLA-A, -B, -D, and -DR matching
  • ABO compatibility is important

Renal:

  • HLA-A and -B matching is significant
  • DR matching improves graft survival
  • C-Ag have limited significance

Heart, Liver, and Lung:
-HLA compatibility has an effect on graft survival

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15
Q

What is the role of HLA in paternity testing?

A

Testing only HLA-A and -B Ags, 90% accurate results obtained.

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16
Q

What is the role of HLA in HTRs?

A
  • Post multiple transfusions w/ blood products, patients can develop Abs to foreign HLA introduced by transfusions, making it hard to find HLA compatible blood match
  • Leukocyte free blood products must be transfused
17
Q

What is the role of HLA in platelet transfusions?

A
  • PTLs contain leukocytes, unless further treated
  • Alloimmunization may cause patients to become refractory to untyped PTL transfusions
  • May lead to PTL Abs in patient and may require HLA matched PTLs
18
Q

Discuss Fetomaternal/Neonatal Alloimmune Thrombocytopenia

A
  1. Pathology:
    - Infant PTLs destroyed due to allo-Ab of mother
    - When infant and father are PL (a1) positive and mother is PL (a1) negative
    - Mother: immunized due to previous transfusions, miscarriages, pregnancy.
    - Anti-PL (a1) is IgG
  2. Clinical features:
    - Partial Rash
    - Severe cases: ICH and death
  3. Lab Diagnosis:
    - PTL count is below 20x10^9/L
    - Other cell counts is normal
19
Q

What is the role of HLA in disease association?

A

-TRALI and TA-GvHD

  • B37: Juvenile Rheumatoid Arthritis
  • A3: Multiple Sclerosis
  • Bw15: Diabetes Mellitus
  • Dw3: Addison’s Disease
  • B8: Chronic active hepatitis

Immunohaematology I (10 decks)

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