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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
What is the thing responsible for release and up regulation in granulopoiesis ?
CXCR2
26
What is release activated by ?
Signalling through CXCR2, TLR and G-CSFR
27
What is a band neutrophil ?
An immature neutrophil which can sometimes leave the bone marrow
28
What does G-CSF stand for ?
Granulocytes conony stimulating factor
29
What is G-CSF ?
A growth or cytokine produced by numerous cell types
30
How does G-CSF mediate its effects ?
By binding to a single homodimer receptor G-CSFR
31
What is G-CSF in the plasma ?
Normally undetecable unless in response to infection
32
What does G-CSF do ?
Stimulate survival, proliferation, differentiation and functions of neutrophils
33
What does G-CSF induce ?
Neutrophil exit from the bone marrow
34
What does G-CSF interfere with ?
CXCR4-CXCL12 interaction
35
What does G-CSF simultaneously induce ?
CXCL1, CXCL2 and CXCL5
36
What are CXCL1, CXCL2, CXCL5 ?
They are ligands for CXCR2 which is highly expressed on the mature polymorphic neutrophil
37
What can inhibit neutrophil apoptosis ?
Locally produced G-CSF in tissue
38
What is G-CSF expression controlled by ?
Phagocytosis of apoptotic neutrophils
39
What does phagocytosis of apoptotic neutrophils do ?
Reduces IL-23 production by macrophages which in turn reduces IL-17 production
40
What does IL-17 production promote ?
Upregulation of G-CSF
41
What is G-CSF used to treat ?
Neutropenia in cancer patients
42
What is chemotaxis ?
The process of cell movement towards its target site
43
What recruits neutrophils to site of infection ?
Generation of chemotactic gradients
44
What is the chemotactic gradient achieved by ?
Production of chemoattractants at the site of infection
45
What can chemoattractants be produced by ?
Host cells and the invading bacteria
46
What can induce chemoattractants ?
Chemokines
47
What are the neutrophil chemoattractants ?
1. Chemotactic lipids 2. Chemokines 3. Complement 3a and C5a 4. Formylated peptides
48
What are chemokines ?
Small souluble proteins
49
What is the structure of a chemokine ?
Contains four cystine residues in conserved locations in their N-terminus
50
What are the four families based on the number of amino acids between first two cysteines ?
1. CXC 2. CC 3. CX3C 4. C
51
What can chemokines do ?
1. Some are pro-inflammatory 2. Others are homeostatic 3. Interact with G-protein coupled receptors
52
What is good at making IL8 ?
Keratinocytes
53
What is involved in leukocye exravasation ?
1. Vasodilation 2. Activation of endothelium 3. Rolling 4. Adhesion 5. Transendothelial migration 6. Migration
54
What are the pathogen recognition receptors ?
1. TLRs 2. Lectin receptors
55
What are the chemokine receptors ?
1. CXCR1 2. CXCR2 complement receptors
56
What are some integrins ?
VLA-4 LFA-1
57
What is an example of the complement receptors ?
CR1-4
58
What are some examples of neutrophil receptors ?
1. Pathogen recognition receptors 2. Chemokine receptors 3. Integrins 4. Complement receptors 5. Fc receptors
59
What are pathogens recognised by ?
Receptors on surface of phagocyte
60
What can happen to pathogens for optimal recognition by phagocyte ?
Opsonisation
61
What is opsonin independent recognition ?
Direct recognition of targets on microbe
62
What does activation of receptors lead to ?
Cytoskeleton rearrangement and pseudopod formation
63
What is the fundamental basis of phagocytosis ?
Rearrangement of actin cytoskeleton
64
What are intracellular signalling pathways triggered by ?
Receptor activation
65
What is the function of PRRs ?
Facilitate recognition and enhance this process by activation of signalling pathways in phagocyte
66
What are the phases of phagocytosis ?
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
What are the neutrophil killing mechanisms ?
1. Release of antimicrobial peptides 2. Acidic environment 3. O2 independent 4. O2 dependent 5. Neutrophil extra-cellular traps
68
What is phagolysosome pH ?
Up regulation of proton pump expression on surface of phagolysosome membrane
69
What is releated to 02 independent killing ?
Neutrophil granules
70
What are neutrophil granules ?
Reservoirs for storing antimicrobial agents and digestive enzymes
71
What is another word for primary granules ?
Azurophil
72
What is in a primary granule ?
1. Myeloperoxidase 2. Defensins 3. Serine proteases: Elastase, cathepsin G
73
What is a secondary (specific) granule ?
1. Lactoferrin 2. Cathelicidin 3. Lysozyme 4. Collagenase
74
What is the tertiary granule ?
1. Gelatinase/MMP9 2. Lysozyme
75
What is found in the secretory granule ?
Cytokine
76
What is used for membrane permebalisation ?
Anti-microbial peptides eg. defensins
77
What hydrolyses proteins in cell membranes ?
Elastase, cathepsin G
78
What can sequester free iron ?
Lactoferrin
79
What targets structural components ?
1. Gelatinase breaks down gelatin 2. Lysosyme targets peptidoglycan
80
What can neutrophil granules do ?
1. Membrane permebalisation 2. Hydrolyse proteins in cell membrane 3. Sequester free iron 4. Target structural components
81
What can NETs cause ?
Pathology
82
What do NETs have ?
Chromatin which contains anti-microbial peptids
83
What type of disease do NETS cause ?
Lupus
84
What is programmed cell death ?
1. Apoptosis 2. Pyroptosis
85
What is non-programmed cell death ?
Necrosis
86
What is neutrophil apoptosis ?
Mechanism by which inflammatory neutrophils are safely removed from site of infection or injury
87
What are the characteristics of apoptosis ?
1. Blebbing 2. Cell shrinkage 3. Alterations in membrane lipids 4. Chromatin condensation 5. DNA fragmentation 6. Cell disintegrates into apoptotic bodies
88
What happens to cell remains in neutrophil apoptosis ?
Contents of the cell remains enclosed within cell membrane
89
What does activation of neutrophil apoptosid require ?
Death signal
90
What is efferocytosis ?
Phagocytosis of apoptotic neutrophils
91
What is necroptosis triggered by?
Cell death receptors
92
What is pyroptosis triggered by ?
Inflammasome activation
93
What is neutrophil necrosis ?
A violent form of cell death caused by external facotrs
94
What effects does neutrophil necrosis have on host tissue ?
Detrimental effects
95
What are the characteristics of neutrophil necrosis ?
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
What does accumulation of apoptotic neutrophils lead to ?
Secondary necrosis

Core Concepts in Immunology (22 decks)

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