Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

williams hEEmatology 10th ed > CHAPTER 137 HUMAN LEUKOCYTE AND PLATELET ANTIGENS > Flashcards

CHAPTER 137 HUMAN LEUKOCYTE AND PLATELET ANTIGENS Flashcards

1
Q

Two major classes of HLA and their examples

A

class I (A, B, and C loci)
class II (DR, DQ, and DP loci)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

primarily expressed on B cells and other antigen-presenting cells such as dendritic cells, endothelial cells, and monocytes

A

class II (DR, DQ, and DP loci)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

human leukocyte antigens play key roles in: (3)

A

1) HSC transplantation acceptance/ rejection

2) allosensitization to non-leukoreduced blood transfusions leading to platelet transfusion refractoriness,

3) lesser, in solid- organ transplantation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

HLA are highly polymorphic glycoproteins encoded by a region of genes known as the major histocompatibility complex (MHC) located on

A

chromosome 6p21

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

T/F: After ABO antigens, HLA antigens are the major barrier to transplantation.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Are ubiquitous and present on most nucleated somatic cells

A

Class I antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Exhibit more restricted distribution, with varying levels of expression on B cells, dendritic cells, monocytes, macrophages, and endothelial cells.

A

Class II antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

T/F: class II antigens can be induced on many cell types through activation.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

nonclassical class Ib antigens
- much less polymorphic
- function less understood

A

HLA-E, HLA-F, and HLA-G

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Antibodies recognizing platelet-specific alloantigens have been discovered in three clinical situations:

A
  1. mothers who give birth to infants with FNAIT;
  2. patients who develop dramatic thrombocytopenia after blood transfusion (PTP);
  3. and patients who have received multiple transfusions.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

principal cause of immunologic platelet transfusion refractoriness

A

class I HLA antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

T/F: occasionally patients receiving multiple platelet transfusions will develop antibodies to platelet specific alloantigens.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

If platelet transfusion refractoriness does develop because of platelet- specific antibodies, compatible platelet products may be identified by: (2)

A

1) using either platelet crossmatching or
2) by accessing family member or other HPA-typed donors who are compatible with the patient’s antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

T/F: Antibodies against some HPA-allelic determinants can inhibit platelet function.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

_____can inhibit clot retraction and platelet aggregation, presumably because they block the binding of GPIIb/IIIa (α β ) (CD41/CD61) to fibrinogen. –> identify the type of platelet function disease

A
  • Anti–HPA-1 alloantibodies,
  • GLANZMANN
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

______, lack platelet GPIb-V-IX (CD 42a-c)

A

Bernard-Soulier syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

_______ can completely inhibit aggregation of HPA-4 platelets that are homozygous for the allele recognized by the alloantibodies because the epitope is in close proximity to the RGD (arginine-glycine-aspartic acid peptide sequence)

A

Anti–HPA-4 alloantibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

T/F: other anti–HPA-alloantibodies, such as those specific for HPA-3, may not significantly interfere with platelet function but nonetheless can cause Fc-mediated platelet destruction and immune thrombocytopenia

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

result from transfusion of antibodies to recipient HPA

A

passive alloimmune thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Transfusion of blood components containing antibodies to ____ and _____ have been reported to result in significant thrombocytopenia for 1 to 2 weeks.

A

HPA-1a and -5b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

T/F: Many of the best-documented platelet-specific antibodies detected in such patients are directed against platelet antigens whose phenotypic frequencies are less than 30% in the blood-donor population.

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Matching Type:
1. Anti–HPA-1 alloantibodies
2. Anti–HPA-3 alloantibodies
3. Anti–HPA-4 alloantibodies
4. Anti–HPA-1a and 5b alloantibodies

a. inhibit aggregation of HPA-4 platelets that are homozygous for the allele recognized by the alloantibodies because the epitope is in close proximity to the RGD
b. result in significant thrombocytopenia for 1 to 2 weeks
c. can inhibit clot retraction and platelet aggregation, presumably because they block the binding of GPIIb/IIIa (α β ) (CD41/CD61)
d. can cause Fc-mediated platelet destruction and immune thrombocytopenia

A

1, c
2, d
3, a
4, b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

The earliest.
Involved mixing of patient serum with normal platelets and used platelet function-dependent end points such as α-granule release, aggregation, or agglutination.

A

Phase I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

the only major phase I assay remaining in wide use today

A

serotonin release assay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

detect either surface or total platelet-associated immunoglobulin on patient platelets or on normal platelets after sensitization with patient serum

A

phase II tests

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

An example of a phase II assay in wide use today:

A

solid-phase red cell adherence test, used for platelet crossmatching

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

developed in which the binding of antibodies to isolated platelet surface GPs is detected.

A

Phase III assays

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

detect alloantibodies in the evaluation of suspected FNAIT and PTP, as well as autoantibodies in some cases of ITP

A

Phase III assays

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Examples of phase III assays (2)

A
  1. monoclonal antibody immobilization of platelet antigens assay (MAIPA)
  2. modified antigen capture ELISA (MACE)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

because of limited access to rare typing sera and the need to establish platelet typing in patients with very few platelets, they have been largely supplanted by _______

A

molecular typing using methods based on PCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Alleles present at gene frequencies greater than 2 percent within the population are designated as ____

A

public alleles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

These alleles are more likely to encode alloantigens involved in PTP.

A

public alleles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

HPA NOMENCLATURE

_____ allele represents the more prevalent form of the protein, while the _____ allele represents the less-common form.

A

a, b

34
Q

HPA-lb is expressed on the platelets of approximately _____ percent of persons of European ancestry but of less than____ percent of persons of Asian ancestry

A

15, 1

35
Q

Type _____ CD36-deficient individuals can become immunized via transfusion or pregnancy and make isoantibodies against CD36 that have been implicated in cases of FNAIT, PTP, and platelet transfusion refractoriness.

A

I

36
Q

T/F CD36 deficiency is common in Asians and Africans, but is rare in white populations.

A

TRUE

37
Q

Platelet GPIV (CD36) is expressed on various human cells including (5)

A

platelets, macrophages, capillary endothelium, erythroblasts, and adipocytes

38
Q

Matching Type

  1. ANN
  2. AIN
  3. TRALI

a. anti–HNA-2 and anti–HNA-3a
b. anti–HNA-1a, anti–HNA-1b and FcγRIIIb epitopes
c. anti–HNA-1a, anti–HNA-1b, anti–HNA-2, anti-FcγRIIIb

A
  1. c
  2. b
  3. a
39
Q
  • neutropenia is detected in the first week of life when the neonate becomes febrile or develops an infection
    -neutrophil count are 0.1 to 0.2 × 109/L.
  • Total WBC , platelet count, and hemoglobin are usually normal, but eosinophilia or monocytosis may be present.
  • occasionally, infant is asymptomatic, but almost all affected children have an infection.
  • The duration of the neutropenia may be as short as a few days or as long as 28 weeks.
    -The mean duration of neutropenia is approximately 11 weeks.
A

Alloimmune Neonatal Neutropenia

40
Q

Pathophysiology of Alloimmune Neonatal Neutropenia

A

During pregnancy, mothers can become alloimmunized to fetal neutrophil antigens. Maternal IgG directed to neutrophils can cross the placenta and destroy the neonate’s neutrophils.

41
Q

T/F: (IVIG) and granulocyte colony-stimulating factor (G-CSF) have a limited role in the treatment of neonatal alloimmune neutropenia

A

TRUE

42
Q

In most cases, children presented with severe neutropenia, having neutrophil counts less than 0.5 × 109/L

Monocytosis has been reported to occur in up to 38 percent of patients.

Marrow biopsies in affected patients usually show normal to hypercellular marrow with a decreased number of mature neutrophils.

A

Autoimmune Neutropenia of Childhood

43
Q

In AIN, the onset of autoimmune neutropenia of children begins at ___months of age

Most studies have found that neutrophil counts recover spontaneously by the age of ____ years, with a median duration of neutropenia of 13 to 20 months.

A

8, 5

44
Q

occurs within 6 hours of a transfusion when hypoxia and noncardiogenic pulmonary edema occur, as measured by a fall in hemoglobin oxygen saturation to less than 90 percent or a partial pressure of arterial oxygen (PaO2)-to-fraction of inspired oxygen (FIO2) ratio (PaO2:FIO2) of less than 300 torr

A

TRALI

45
Q

T/F Febrile nonhemolytic transfusion reactions occur within a few hours of a transfusion and can be associated with chills and rigors.

A

T

46
Q

Matching Type

  1. are expressed only on neutrophils
  2. expressed on neutrophils and subpopulations of neutrophils
  3. neutrophils, lymphocytes, platelets, endothelial cells, kidney, spleen, and placental cells.

a. HNA 2
b. HNA 1
c. HNA 3

A

1, b
2, a
3, c

47
Q
  • previously known as Mart(a)
  • located on the αM chain (CD11b) of the C3bi receptor (CR3)
  • caused by a single nucleotide substitution of G-to-A at position 30283 (Arg->His 61)
  • significance unknown
A

HNA 4

48
Q
  • first described as Ond(a)
  • ound to be expressed on the αL integrin unit, leukocyte function antigen-1 (CD11a),
  • result of a G-to-C single nucleotide substitution at position 2446 (Arg-> Thr at 766)
A

HNA 5

49
Q

result of a single nucleotide change in choline transporter-like protein-2 gene (SLC44A2) at nucleotide 455, which results in an amino acid change at position 152

A

HNA 3

50
Q

Role of NB1 Glycoprotein in Neutrophil Function
(3)

A

binds to platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) and functions as a cell adhesion molecule.

important in the migration of neutrophils through endothelial cells.

involved with neutrophil–endothelial cell interaction

51
Q

T/F: CD177 mRNA is overexpressed by neutrophils from patients with polycythemia rubra vera and essential thrombocytosis, but the expression of HNA-2 is not.

A

TRUE

52
Q

gene encoding NB1 glycoprotein, ____, is located on chromosome ____

A

CD 177
19q13.31

53
Q

HNA 1
_____ of neutrophilic metamyelocytes, and on approximately ____ of neutrophilic myelocytes

A

one-half
10%

54
Q

T/F The four HNA-1 system antigens are encoded by three alleles.

A

True

55
Q

The antigen frequencies of three of the alleles vary widely among different racial groups.
Among whites, _____ is the most common antigen, but in Japanese and Chinese populations ____ is most common.

A

HNA-1b
HNA-1a

56
Q

Function of HNA-1 Antigens

A

Neutrophils that are homozygous for HNA-1b have a lower affinity for immunoglobulin (Ig) G3 than those homozygous for HNA-1a.

Neutrophils from those who are homozygous for HNA-1b phagocytize erythrocytes sensitized with IgG1 and IgG3 anti-Rh monoclonal antibodies and bacteria opsonized with IgG1 at a lower level than neutrophils homozygous for HNA-1a.

57
Q

Patients requiring platelet transfusions may be broadly sensitized to _____ (i.e., have high PRA) through prior transfusions (particularly nonleukoreduced) or pregnancies.

A

HLA-A, and -B

58
Q

_____ ankylosing spondylitis
_____ narcolepsy
_____ associated with hypersensitivity to abacavir

A

HLA- B27
HLA-DQ2
HLA-B*5701

59
Q

The HLA antigens coded by the MHC play a central role in
(3)

A
  1. transplantation - most common application
  2. regulation of immune responses, and
  3. susceptibility to a variety of diseases.
60
Q

HLA typing for matching of kidneys and pancreas is performed at the ________ loci at low resolution (serologic or antigen level by DNA).

A

HLA-A, HLA-B, and HLA-DR

61
Q

T/F: HLA matching is not prospectively performed for hepatic or cardiac transplantation.

A

TRUE

62
Q

_____ and ______ prime importance for kidney and heart transplants where its existence could cause a hyperacute rejection and graft failure.

A

Detection of alloantibody by screening techniques and the donor specific crossmatch

63
Q

T/F In HSC, the graft may recognize the host tissue as foreign and mount an immune response resulting graft-versus-host disease (GVHD)

A

T

64
Q

HUMAN LEUKOCYTE ANTIGEN TYPING

Tissue typing for HLA antigens can be performed by various methods using (3) technologies

A

serologic, cellular, and molecular

65
Q

common prior to the widespread adoption of DNA methods.

are labor-intensive and require the use of radioisotopes;

mainly used in research laboratories.

A

Cellular assays

66
Q

Cellular assays

A

mixed lymphocyte reaction and the primed lymphocyte test

67
Q

a suspension of lymphocytes is incubated with human alloantisera or monoclonal antibody in a microtiter tray.

A

CDC

68
Q

test has been a fundamental procedure for defining HLA antigens for more than 30 years

A

CDC

69
Q

Serology for class II (DR and DQ) antigens requires enrichment for B lymphocytes, which can be accomplished with antibody or _____

A

immunomagnetic bead reagents.

70
Q

involve amplification of genomic DNA from selected portions of HLA genes with oligonucleotide primer pairs

A

PCR

71
Q

primarily of clinical interest in marrow/blood stem cell transplantation.

A

Molecular HLA typing

72
Q

described as massively parallel allowing for many overlapping reads of the same sequence area

A

NGS

73
Q

This is very important for solid-organ transplantation where the presence of ______ can cause irreversible rejection upon transplantation.

A

detection of antibodies to HLA antigens.

74
Q

have become standard practice as they are more sensitive than the CDC method.

A

solid phase assays

75
Q

T/F The α chain of HLA-DR is constant for all HLA-DR molecules, whereas the β chain is polymorphic and determines specificity of the molecule.

A

T

76
Q

Class II molecules: extracellular regions of each chain contain only two domains. The two domains of the α chain are designated α1 and α2, and the two domains of the β-chain are called β1 and β2.

In all class II antigens the______represents the most polymorphic region.

A

β1 domain

77
Q

Class I Antigens

Antigenicity resides in the_____, the areas of highest polymorphism

A

α1 and α2 domains

78
Q

T/F
Platelets express HLA-A antigens, but lack some HLA-B and most HLA-C antigens.

A

T

79
Q

Include genes that encode other proteins that participate in immune response such as complement, heat shock proteins, tumor necrosis factor, and other lymphocyte antigens.

A

class III genes

80
Q

Class____ genes are the most centromeric
Telomeric are the class____ genes

A

II
I

williams hEEmatology 10th ed (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions