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Core Concepts in Immunology > Lecture 6. Neutrophils > Flashcards

Lecture 6. Neutrophils Flashcards

1
Q

What are the two types of leukocytes ?

A
  1. Grnaulocytes
  2. Agranulocytes
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2
Q

What are the three types of granulocytes ?

A
  1. Neutrophils
  2. Eosinophils
  3. Basophils
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3
Q

What are the two types of agranulocytes ?

A
  1. Monocytes
  2. Lymphocytes
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4
Q

Where are neutrophils generated ?

A

In bone marrow

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5
Q

What sort of lifespan do neutrophils have ?

A

Short life span about 18 hours

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6
Q

What happens at the end of a neutrophils lifespan in tissues ?

A

They are cleared or removed

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7
Q

Why do the number of neutrophils in circulation remain relatively constant ?

A

Due to the fine balance between production and elimination

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8
Q

Why must neutrophils clearance mechanisms be tightly regulated ?

A

Because of their cytotoxic contents

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9
Q

What is the structure of a neutrophil ?

A

They are multi-nucleated

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10
Q

What is the structure of the nucleus in a neutrophil ?

A

Clearly visible and consists of three to five lobes connected by chromatin

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11
Q

What are the four types of granules found in the cytoplasm of the neutrophil ?

A
  1. Primary - azurophic
  2. Secondary - specific
  3. Tertiary - gelatinase
  4. Secretory
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12
Q

What are the neutrophils in terms of defence ?

A

The first line of defense

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13
Q

What is the role of the neutrophil in the innate immune system ?

A

Critical effector cell

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14
Q

What do neutrophils patrol the organisms for ?

A

Signs of microbial invasion and when detected, react rapidly to trap and kill invading organisms

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15
Q

What are the primary anti-microbial functions of the neutrophil ?

A
  1. Phagocytosis
  2. Degranulation
  3. Release of neutrophil extracellular traps (NETs)
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16
Q

What do neutrophils pay a detrimental role in ?

A

Pathogenesis of acute and chronic inflammatory disease

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17
Q

What can neutrophils inform or regulate ?

A

Immune responses for example release cytokines and chemokines

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18
Q

What do neutrophils comprise of ?

A

Multiple phenotypes (immunostimulatroy and immunosupressive) or subsets that change with time as they mature or age and also depending on the tissue microenvironment

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19
Q

What is the most important cell in fighting extra-cellulalar bacterial infection ?

A

Neutrophil

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20
Q

How many stages is there in formulation of granular leukocytes ?

A

Five

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21
Q

What is granulopoiesis ?

A

The formation of granular leukocytes

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22
Q

What are all stages of granulooiesis controlled by ?

A

Expression of specific transcription factors which direct the formation of granules

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23
Q

What is the retention/release of cells from the bone marrow controlled by ?

A

Chemokine receptors

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24
Q

What is the thing responsible for retention and down regulation in granulopoiesis ?

A

CXCR4

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25
Q

What is the thing responsible for release and up regulation in granulopoiesis ?

A

CXCR2

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26
Q

What is release activated by ?

A

Signalling through CXCR2, TLR and G-CSFR

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27
Q

What is a band neutrophil ?

A

An immature neutrophil which can sometimes leave the bone marrow

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28
Q

What does G-CSF stand for ?

A

Granulocytes conony stimulating factor

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29
Q

What is G-CSF ?

A

A growth or cytokine produced by numerous cell types

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30
Q

How does G-CSF mediate its effects ?

A

By binding to a single homodimer receptor G-CSFR

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31
Q

What is G-CSF in the plasma ?

A

Normally undetecable unless in response to infection

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32
Q

What does G-CSF do ?

A

Stimulate survival, proliferation, differentiation and functions of neutrophils

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33
Q

What does G-CSF induce ?

A

Neutrophil exit from the bone marrow

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34
Q

What does G-CSF interfere with ?

A

CXCR4-CXCL12 interaction

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35
Q

What does G-CSF simultaneously induce ?

A

CXCL1, CXCL2 and CXCL5

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36
Q

What are CXCL1, CXCL2, CXCL5 ?

A

They are ligands for CXCR2 which is highly expressed on the mature polymorphic neutrophil

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37
Q

What can inhibit neutrophil apoptosis ?

A

Locally produced G-CSF in tissue

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38
Q

What is G-CSF expression controlled by ?

A

Phagocytosis of apoptotic neutrophils

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39
Q

What does phagocytosis of apoptotic neutrophils do ?

A

Reduces IL-23 production by macrophages which in turn reduces IL-17 production

40
Q

What does IL-17 production promote ?

A

Upregulation of G-CSF

41
Q

What is G-CSF used to treat ?

A

Neutropenia in cancer patients

42
Q

What is chemotaxis ?

A

The process of cell movement towards its target site

43
Q

What recruits neutrophils to site of infection ?

A

Generation of chemotactic gradients

44
Q

What is the chemotactic gradient achieved by ?

A

Production of chemoattractants at the site of infection

45
Q

What can chemoattractants be produced by ?

A

Host cells and the invading bacteria

46
Q

What can induce chemoattractants ?

A

Chemokines

47
Q

What are the neutrophil chemoattractants ?

A
  1. Chemotactic lipids
  2. Chemokines
  3. Complement 3a and C5a
  4. Formylated peptides
48
Q

What are chemokines ?

A

Small souluble proteins

49
Q

What is the structure of a chemokine ?

A

Contains four cystine residues in conserved locations in their N-terminus

50
Q

What are the four families based on the number of amino acids between first two cysteines ?

A
  1. CXC
  2. CC
  3. CX3C
  4. C
51
Q

What can chemokines do ?

A
  1. Some are pro-inflammatory
  2. Others are homeostatic
  3. Interact with G-protein coupled receptors
52
Q

What is good at making IL8 ?

A

Keratinocytes

53
Q

What is involved in leukocye exravasation ?

A
  1. Vasodilation
  2. Activation of endothelium
  3. Rolling
  4. Adhesion
  5. Transendothelial migration
  6. Migration
54
Q

What are the pathogen recognition receptors ?

A
  1. TLRs
  2. Lectin receptors
55
Q

What are the chemokine receptors ?

A
  1. CXCR1
  2. CXCR2 complement receptors
56
Q

What are some integrins ?

A

VLA-4 LFA-1

57
Q

What is an example of the complement receptors ?

58
Q

What are some examples of neutrophil receptors ?

A
  1. Pathogen recognition receptors
  2. Chemokine receptors
  3. Integrins
  4. Complement receptors
  5. Fc receptors
59
Q

What are pathogens recognised by ?

A

Receptors on surface of phagocyte

60
Q

What can happen to pathogens for optimal recognition by phagocyte ?

A

Opsonisation

61
Q

What is opsonin independent recognition ?

A

Direct recognition of targets on microbe

62
Q

What does activation of receptors lead to ?

A

Cytoskeleton rearrangement and pseudopod formation

63
Q

What is the fundamental basis of phagocytosis ?

A

Rearrangement of actin cytoskeleton

64
Q

What are intracellular signalling pathways triggered by ?

A

Receptor activation

65
Q

What is the function of PRRs ?

A

Facilitate recognition and enhance this process by activation of signalling pathways in phagocyte

66
Q

What are the phases of phagocytosis ?

A
  1. Adherence and activation of phagocyte receptors
  2. Pseudopods extend and engulf bacteria
  3. Formation of phagosome
  4. Fusion of phagosome with lysosome to form phagolysosome
  5. Killing of ingested bacteria
67
Q

What are the neutrophil killing mechanisms ?

A
  1. Release of antimicrobial peptides
  2. Acidic environment
  3. O2 independent
  4. O2 dependent
  5. Neutrophil extra-cellular traps
68
Q

What is phagolysosome pH ?

A

Up regulation of proton pump expression on surface of phagolysosome membrane

69
Q

What is releated to 02 independent killing ?

A

Neutrophil granules

70
Q

What are neutrophil granules ?

A

Reservoirs for storing antimicrobial agents and digestive enzymes

71
Q

What is another word for primary granules ?

72
Q

What is in a primary granule ?

A
  1. Myeloperoxidase
  2. Defensins
  3. Serine proteases: Elastase, cathepsin G
73
Q

What is a secondary (specific) granule ?

A
  1. Lactoferrin
  2. Cathelicidin
  3. Lysozyme
  4. Collagenase
74
Q

What is the tertiary granule ?

A
  1. Gelatinase/MMP9
  2. Lysozyme
75
Q

What is found in the secretory granule ?

76
Q

What is used for membrane permebalisation ?

A

Anti-microbial peptides eg. defensins

77
Q

What hydrolyses proteins in cell membranes ?

A

Elastase, cathepsin G

78
Q

What can sequester free iron ?

A

Lactoferrin

79
Q

What targets structural components ?

A
  1. Gelatinase breaks down gelatin
  2. Lysosyme targets peptidoglycan
80
Q

What can neutrophil granules do ?

A
  1. Membrane permebalisation
  2. Hydrolyse proteins in cell membrane
  3. Sequester free iron
  4. Target structural components
81
Q

What can NETs cause ?

82
Q

What do NETs have ?

A

Chromatin which contains anti-microbial peptids

83
Q

What type of disease do NETS cause ?

84
Q

What is programmed cell death ?

A
  1. Apoptosis
  2. Pyroptosis
85
Q

What is non-programmed cell death ?

86
Q

What is neutrophil apoptosis ?

A

Mechanism by which inflammatory neutrophils are safely removed from site of infection or injury

87
Q

What are the characteristics of apoptosis ?

A
  1. Blebbing
  2. Cell shrinkage
  3. Alterations in membrane lipids
  4. Chromatin condensation
  5. DNA fragmentation
  6. Cell disintegrates into apoptotic bodies
88
Q

What happens to cell remains in neutrophil apoptosis ?

A

Contents of the cell remains enclosed within cell membrane

89
Q

What does activation of neutrophil apoptosid require ?

A

Death signal

90
Q

What is efferocytosis ?

A

Phagocytosis of apoptotic neutrophils

91
Q

What is necroptosis triggered by?

A

Cell death receptors

92
Q

What is pyroptosis triggered by ?

A

Inflammasome activation

93
Q

What is neutrophil necrosis ?

A

A violent form of cell death caused by external facotrs

94
Q

What effects does neutrophil necrosis have on host tissue ?

A

Detrimental effects

95
Q

What are the characteristics of neutrophil necrosis ?

A
  1. Rupturing of cell membranes
  2. Cell swelling
  3. Random destruction of cellular structures
  4. Holes in cell membrane
  5. Cytosolic proteins released from dying cell
96
Q

What does accumulation of apoptotic neutrophils lead to ?

A

Secondary necrosis

Core Concepts in Immunology (22 decks)

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