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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
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
33
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

Year 1 (48 decks)

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