HLA Flashcards

1
Q

What is Human Leukocyte antigen testing
(3)

A

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

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2
Q

What is the HLA genetic region
(3)

A

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

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3
Q

How many classes of MHC are there

A

3 classes

MHC class I, II, III

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4
Q

What are the three loci of class III

A

DP
DQ
DR

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5
Q

What are the three loci of class I

A

A
B
C

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6
Q

What are some applications of HLA testing?

A

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

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7
Q

What did we used to use HLA testing mainly for?

A

Paternity
Forensics

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8
Q

When would it be important to determine HLA antigen composition
(3)

A

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

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9
Q

How is HLA expressed

A

Two codominant alleles for each locus

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10
Q

Write about the two codominant alleles for each locus

A

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

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11
Q

What is haplotype

A

This refers to the allelic makeup of a single chromosome

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12
Q

Write about linkage disequilibrium
(2)

A

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

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13
Q

What are HLA gene products

A

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)

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14
Q

Where are class I molecules

A

Present on all nucleated cells, dendritic cells and platelets

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15
Q

Where are class II molecules found

A

Present only on B lymphocytes, activated T lymphocytes, macrophages, monocytes and endothelial cells

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16
Q

Write about the function of the HLA system

A

Role in the adaptive arm of the immune system
Recognition and elimination of foreign antigens
Self and non-self discrimination
Large degree of polymorphism seen in MHC
Thought to have evolved to present a large range of foreign peptide antigens

17
Q

Write about HLA and transfusion issues
(6)

A

Disparity in HLA groups between donor and recipient leucocytes may stimulate production of HLA antibodies

These antibodies may cause ‘Febrile’ non haemolytic transfusion reactions by complexing with antigen and resulting in WBC destruction and release of pyrogens

They may also compromise future transplants in multi-transfused patients

All ‘cellular’ blood products contain leucocytes-hence benefit of leucodepletion

HLA antibodies are important in TRALI

HLA antibodies may reduce the efficiency of platelet transfusions -> causes refractoriness and the need for HLA matched platelets

18
Q

What reactions can HLA antibodies cause
(4)

A

Implicated in acute and delayed HTRs

Not in HDFN

Platelet reactions

TRALI