Leukocyte Structure and Function Flashcards

1
Q

What does leukocyte activation require?

A

A change in morphology and behavior from extracellular signal

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2
Q

cell surface markers expressed on surface of all blood cells (leukocytes)

A

<p>CD antigens (cluster of differentiation)</p>

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3
Q

Primary cells of innate immunity

A

Myeloid cells

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4
Q

There are about 5,000-10,000 total leukocytes (cells/ul) circulating. Which type make up the most? Which make up the least?

A

Neutrophils- 55-70%

Basophiles-0.5-1%

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5
Q

This type of leukocyte has a really round nucleus, almost same size as cytoplasm

A

Lymphocyte

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6
Q

This cell has a segmented nucleus, but it stains dark in H/S stain you probably can’t see it

A

basophil

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7
Q

What is the activated function of neutrophil?

A

Phagocytosis and activation of bactericidal mechanisms

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8
Q

Are neutrophils short lived or long lived?

A

Short lived; circulate for a few hours, undergo apoptosis/necrosis

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9
Q

How many rounds of phagocytosis do neutrophils undergo before cell death?

A

ONE. A single one.

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10
Q

What clears out dead neutrophils?

A

Tissue macrophages

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11
Q

What is the chief cell of acute inflammation?

A

Neutrophils

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12
Q

These molecules are associated with groups of pathogens, recognized by cells of innate immune system

A

PAMPs “pathogen associated molecular patterns”

DAMPs “danger associated”

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13
Q

All neutrophils express this integral membrane protein on their surface to recognize pathogens

A

Mannose receptor

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14
Q

This term describes the rapid release of reactive oxygen species and NADPH-oxidase subunites to destroy internalized bacteria

A

Respiratory or oxidative burst

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15
Q

This is a small vesicle that contains the bacterium inside

A

phagosome

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16
Q

What is a lysosome fuzed with phagosome called?

A

Phagolysosome

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17
Q

What do tertiary neutrophil granules contain?

A

Gelitinase (MMP-9)

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18
Q

What are the characteristics and role of primary / azurophilic neutrophil granules?

A

Dark staining, antimicrobial proteins, fuse with endosomes and empty contents. Kill ingested bacteria

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19
Q

What are the characteristics and role of secondary/specific/definitive neutrophil granules?

A

Pale, fuse with endosome, trigger respiratory burst. Release contents extracellulary

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20
Q

What are 3 important consequences of the Respiratory Burst?

A
  1. Increase oxygen consumption
  2. production of superoxide O2-
  3. Production of hydrogen peroxide (H2O2) and other bactericidal reactive oxygen species (ROS)
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21
Q

What is the primary azurophilic neutrophil granule?

What is another important one?

A
Myeloperoxide (MO)
Sulfated Proteoglycan (Sulfated PG)
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22
Q

NADPH oxidase, sometimes called “phagocytic oxidase,” is in the walls of which neutrophil granule?

A

Secondary granules

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23
Q

How many subunits does NADPH oxidase have? How amny are in cytoplasm? Which ones?

A

5 subunits, 3 in cytoplasm: p40phox, p45, p67

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24
Q

What is the membrane bound component of the NADPH oxidase?

A

flavocytochrome b (consists of 2 subunits: gp22phox, gp91 phox)

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25
Q

Once activated, NADPH oxidase converts oxygen molecules to what?

A

Superoxide, O2-

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26
Q

What enzyme converts superoxide to hydrogen peroxide?

A

Superoxide dismutase

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27
Q

What enzyme breaks down hydrogen peroxide to hypochloric acid? (HOCL-)

A

Myeloperoxidase (MPO)-

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28
Q

This enzyme breaks down hydrogen peroxide to benign components such as water and oxygen

A

Catalase

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29
Q

Mutations in NADPH oxidase underlie what disease?

A

Chronic Granulomatous Disease (can be autosomal recessive or X-linked if mutation of gp91)

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30
Q

How do neutrophils aid in infection control and wound healing?

A

Release mediators to destroy damaged tissue; disassemble matrix proteins to allow neutrophil-microbe interaction; prevent microbe escape

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31
Q

How do matrix metalloproteinases (MMPs) contribute to tissue destruction from chronic inflammation?

A

Inflammation causes cytokines to attract more leukocytes, MMPS digest ECM&raquo_space; tissue destruction

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32
Q

Both of these cells release histamine and have surface receptors for antibody

A

Mast cells and basophils

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33
Q

Basophil or Mast cell? Recruited to tissue

A

Basophils

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34
Q

Basophil or Mast cell? Source of tissue histamine

A

Mast cell

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35
Q

Basophil or Mast cell? Complete maturation in tissues

A

Mast cell

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36
Q

Basophil or Mast cell? Resident in tissues

A

Mast cell

37
Q

Source of blood histamine

A

Basophil

38
Q

Basophil or Mast cell? Circulate as mature cells

A

Basophil

39
Q

Monocyte Inflammatory phase (3)

A

inflammatory trafficking, phagocytosis, proteolysis

40
Q

Monocyte Reparative phase (2)

A

Patrol for signs of damage, wound clean up and repair

41
Q

CD14

A

inflammatory phase monocyte

42
Q

CD16

A

reparative phase monocyte

43
Q

Once in damaged tissue, monocytes polarize two these two primary types

A

Macrophages (M1 and M2)

44
Q

4 major functions of Macrophages

A

Scavengers, Secretory cells, Regulate, Antigen-presenting cells

(R ASS)

45
Q

Inflammatory monocytes become what type of macrophage?

A

M1

46
Q

Reparative monocytes become what type of macrophage?

A

M2

47
Q

M1 or M2? Remove dead cells

A

M1

48
Q

M1 or M2? Suppress inflammation

A

M2

49
Q

M1 or M2? Pro-inflammatory cytokines

A

M1

50
Q

M1 or M2? Stimulate inflammation

A

M1

51
Q

M1 or M2? Anti-inflammatory cytokines

A

M2

52
Q

M1 or M2? Promote angiogenesis

A

M2

53
Q

Monocyte/Macrophage or Neutrophil?

Long lived-weeks/months

A

M/M

54
Q

Monocyte/Macrophage or Neutrophil?

Short lived-hours

A

Neutrophil

55
Q

Monocyte/Macrophage or Neutrophil?

Self-replicating and adaptable

A

M/M

56
Q

Monocyte/Macrophage or Neutrophil?

End stage cells with a single function

A

Neutrophil

57
Q

Monocyte/Macrophage or Neutrophil?

Accumulate slowly, persist longer

A

M/M

58
Q

Monocyte/Macrophage or Neutrophil?

Accumulate quickly, short lived

A

Neutrophil

59
Q

Monocyte/Macrophage or Neutrophil?

Modest metabolic burst

A

M/M

60
Q

Monocyte/Macrophage or Neutrophil?

Stronger metabolic burst

A

Neutrohil

61
Q

Reticulo-endothelial system

A

Resident macrophages

62
Q

Site of fluid exchange and inflammatory trafficking (leukocyte migration)

A

Capillary beds of veins

63
Q

What causes leukocytes to stick and roll along vessel walls?

A

Selectins expressed by endothelial cells

64
Q

What are the four adhesion molecule CAM families? Which bind with which?

A

SelectinsMucin-like CAMs

Integrins Ig-superfamily CAMs

65
Q

Soluble cytokines

A

Chemokines

66
Q

Inflammation is controlled by what interaction?

A

Cell surface adhesion molecules (CAMs) and chemokines and their receptors on endothelial cells and leukocytes regulate migration in and out of tissue

67
Q

Proteins are classified as chemokines due to shared small shape. What is important in forming their 3-D shape?

A

Presence of 4 cysteine residues

68
Q

Inflammation exacerbates disease. List 8 (A CAN PACT)

A

Alzheimers, Cancer, Arthritis, Neurological diseases, Pulmonary diseases, Autoimmune diseases, cardiovascular diseases, Type II diabetes

69
Q

These G-protein coupled receptor’s main function is to attract leukocytes and activate adhesion

A

Chemokine

70
Q

a tetrasaccharide carbohydrate that is attached to O-glycans on the surface of endothelial cells or ECM molecules, involved in capture/tethering and rolling part of trafficking

A

Sialyl Lewis X (s-Lex)

71
Q

This protein functions as a CAM on the surfaces of activated endothelial cells (or ECM), and expressed very early in rolling stage

A

P selectin (along with E-selectin and s-Lex)

72
Q

True or false: in the multi step model for leukocyte trafficking, the steps are overlapping and combinatorial

A

TRUE.

73
Q

True or false: in the mutli step model for leukocyte trafficking, the components play only one role in a single step

A

FALSE. They can play more than one role in multiple steps

74
Q

What accounts for the specificity and diversity in migration in the multi-step model?

A

It is due to the differential expression and modification of the components

75
Q

What are the 7 steps of mult-step model of Leukocyte trafficking?

A

Capture, Rolling, Activation, Adhesion, Diapedesis, Traversing Basal Lamina, Migration through ECM

76
Q

What are the interactions in rolling? What is the strength and why

A

Selectins (E and P) interact with leukocyte sialyl-lewis-x, it is a weak interaction to allow rolling

77
Q

What adhesion molecules (ligands) of the endothelium will interact with leukocyte’s integrin LFA-1 during adhesion?

A

ICAM-1 and ICAM-2

78
Q

In capturing phase, what part of leukocyte binds with what part of endothelial cell?

A

L-selectin binds with s-Lex

79
Q

Strong interactions are achieved by what two types of signaling?

A

Outside-in signaling, and inside-out

80
Q

What makes up outside-in signaling?

A

Chemokines from endothelium signal through G-protein coupled receptors

81
Q

What make up inside-out signaling?

A

Integrins are activated and allow for tight interaction with ICAMs on endothelium

82
Q

Takes 90 seconds and requires disassembly/reassembly of both leukocytes and endothelial cytoskeleton

A

Diapedesis

83
Q

Describe the adhesion molecule zipper

A

Endothelial tight junctions open up like a zipper, form new junctions between leukocyte and endothelium without any leak

84
Q

During intercellular diapedesis, the “transmigratory cup” forms. What are the three important molecules involved?

A

Integrin, ICAM-1, VCAM-1

85
Q

During transcellular diapedesis, what are the three important molecules involved?

A

VE-cadherin (vascular endothelial, CD144)
ICAM-1
LFA-1 (lymphocyte function-associated antigen 1)

86
Q

In lymph nodes, what do T-cells require to be activated and go into the specific T-cell area?

A

Chemokines

87
Q

When macrophages attack the pathogen/bacteria that has entered at the site of injury/inflammation, it releases this important cytokine

A

TNFa (tumor-necrosis factor alpha) (along with IL-6, IL-1, and IL-8)

88
Q

Why is TNF-a considered a pro-inflammatory cytokine?

A

It activates receptors on the blood vessel endothelium