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Flashcards in Leukocyte Structure and Function Deck (88):
1

What does leukocyte activation require?

A change in morphology and behavior from extracellular signal

2

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

CD antigens (cluster of differentiation)

3

Primary cells of innate immunity

Myeloid cells

4

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

Neutrophils- 55-70%
Basophiles-0.5-1%

5

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

Lymphocyte

6

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

basophil

7

What is the activated function of neutrophil?

Phagocytosis and activation of bactericidal mechanisms

8

Are neutrophils short lived or long lived?

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

9

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

ONE. A single one.

10

What clears out dead neutrophils?

Tissue macrophages

11

What is the chief cell of acute inflammation?

Neutrophils

12

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

PAMPs "pathogen associated molecular patterns"
DAMPs "danger associated"

13

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

Mannose receptor

14

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

Respiratory or oxidative burst

15

This is a small vesicle that contains the bacterium inside

phagosome

16

What is a lysosome fuzed with phagosome called?

Phagolysosome

17

What do tertiary neutrophil granules contain?

Gelitinase (MMP-9)

18

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

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

19

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

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

20

What are 3 important consequences of the Respiratory Burst?

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

21

What is the primary azurophilic neutrophil granule?
What is another important one?

Myeloperoxide (MO)
Sulfated Proteoglycan (Sulfated PG)

22

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

Secondary granules

23

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

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

24

What is the membrane bound component of the NADPH oxidase?

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

25

Once activated, NADPH oxidase converts oxygen molecules to what?

Superoxide, O2-

26

What enzyme converts superoxide to hydrogen peroxide?

Superoxide dismutase

27

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

Myeloperoxidase (MPO)-

28

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

Catalase

29

Mutations in NADPH oxidase underlie what disease?

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

30

How do neutrophils aid in infection control and wound healing?

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

31

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

Inflammation causes cytokines to attract more leukocytes, MMPS digest ECM >> tissue destruction

32

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

Mast cells and basophils

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Basophil or Mast cell? Recruited to tissue

Basophils

34

Basophil or Mast cell? Source of tissue histamine

Mast cell

35

Basophil or Mast cell? Complete maturation in tissues

Mast cell

36

Basophil or Mast cell? Resident in tissues

Mast cell

37

Source of blood histamine

Basophil

38

Basophil or Mast cell? Circulate as mature cells

Basophil

39

Monocyte Inflammatory phase (3)

inflammatory trafficking, phagocytosis, proteolysis

40

Monocyte Reparative phase (2)

Patrol for signs of damage, wound clean up and repair

41

CD14

inflammatory phase monocyte

42

CD16

reparative phase monocyte

43

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

Macrophages (M1 and M2)

44

4 major functions of Macrophages

Scavengers, Secretory cells, Regulate, Antigen-presenting cells

(R ASS)

45

Inflammatory monocytes become what type of macrophage?

M1

46

Reparative monocytes become what type of macrophage?

M2

47

M1 or M2? Remove dead cells

M1

48

M1 or M2? Suppress inflammation

M2

49

M1 or M2? Pro-inflammatory cytokines

M1

50

M1 or M2? Stimulate inflammation

M1

51

M1 or M2? Anti-inflammatory cytokines

M2

52

M1 or M2? Promote angiogenesis

M2

53

Monocyte/Macrophage or Neutrophil?
Long lived-weeks/months

M/M

54

Monocyte/Macrophage or Neutrophil?
Short lived-hours

Neutrophil

55

Monocyte/Macrophage or Neutrophil?
Self-replicating and adaptable

M/M

56

Monocyte/Macrophage or Neutrophil?
End stage cells with a single function

Neutrophil

57

Monocyte/Macrophage or Neutrophil?
Accumulate slowly, persist longer

M/M

58

Monocyte/Macrophage or Neutrophil?
Accumulate quickly, short lived

Neutrophil

59

Monocyte/Macrophage or Neutrophil?
Modest metabolic burst

M/M

60

Monocyte/Macrophage or Neutrophil?
Stronger metabolic burst

Neutrohil

61

Reticulo-endothelial system

Resident macrophages

62

Site of fluid exchange and inflammatory trafficking (leukocyte migration)

Capillary beds of veins

63

What causes leukocytes to stick and roll along vessel walls?

Selectins expressed by endothelial cells

64

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

SelectinsMucin-like CAMs
Integrins Ig-superfamily CAMs

65

Soluble cytokines

Chemokines

66

Inflammation is controlled by what interaction?

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

67

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

Presence of 4 cysteine residues

68

Inflammation exacerbates disease. List 8 (A CAN PACT)

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

69

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

Chemokine

70

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

Sialyl Lewis X (s-Lex)

71

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

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

72

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

TRUE.

73

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

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

74

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

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

75

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

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

76

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

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

77

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

ICAM-1 and ICAM-2

78

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

L-selectin binds with s-Lex

79

Strong interactions are achieved by what two types of signaling?

Outside-in signaling, and inside-out

80

What makes up outside-in signaling?

Chemokines from endothelium signal through G-protein coupled receptors

81

What make up inside-out signaling?

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

82

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

Diapedesis

83

Describe the adhesion molecule zipper

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

84

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

Integrin, ICAM-1, VCAM-1

85

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

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

86

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

Chemokines

87

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

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

88

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

It activates receptors on the blood vessel endothelium