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Core Concepts in Immunology > Lecture 7. Monocytes and Macrophages > Flashcards

Lecture 7. Monocytes and Macrophages Flashcards

1
Q

What causes increased heat and swelling

A

Vasodilation and increased vascular permeability

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2
Q

What causes dilation of local and small blood vessels ?

A

Cytokines

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3
Q

What happens due to increased expression of adhesion molecules by the endothelium ?

A

Leukocytes move to periphery of blood vessels

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4
Q

Where do leukocytes extravasate ?

A

At the site of infection

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5
Q

Where does blood clotting occur ?

A

In the microvessels

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6
Q

What are involved in monocyte recruitment particularly adhesion molecules ?

A
  1. Cell surface expressed ligand
  2. Endothelium expressed receptor/binding partner
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7
Q

What does an activated endothelium increase /

A

Expression of many alveolar macrophages

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8
Q

What do chemokine gradients do in monocyte recruitment particularly in adhesion molecules ?

A

Up regulate monocyte expression

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9
Q

What is the rolling attachment step in monocyte recruitmeny particularly adhesion molecules ?

A

Selectin expression on endothelial cell - non specifically attracts leukocytes

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10
Q

What is the arrest adhesion step in monocyte recruitment ?

A

CR3 also called Mac1 binds ICAM1/2

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11
Q

What is diapedesis ?

A

The passage of blood cells through intact walls of capillaries

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12
Q

What produced chemokines ?

A

Local macrophages or activated endothelium

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13
Q

What is the attracted cell determined by ?

A

Receptor specificity

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14
Q

What do monocytes express in terms of chemokines ?

A

CCR2B, CCR1,3,5,

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15
Q

What do CCR2B and CCR1,3,5 follow gradients towards ?

A
  1. CCL2
  2. CCL3
  3. CCL4
    4.CCL5
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16
Q

What does integrin activation alter ?

A

Cytoskeletal dynamic and facilitate diapadesis

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17
Q

What happens after monocytes enter the tissue ?

A

They follow chemokine gradient to the site of inflammation

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18
Q

What is the key factor in maturation ?

A

CSF-1

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19
Q

How does the mature macrophage become activated ?

A

By local signals/cytokines that determine the function

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20
Q

What are the resident/recruited macrophages specialised to do ?

A

Sample, detect and respond to danger via phagocytosis

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21
Q

What is the importance of phagocytosis for immunity ?

A
  1. Elimination/killing of pathogens
  2. Antigen generation
  3. Induction of pro-inflammatory signalling
  4. Resolve inflammation
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22
Q

What are both macrophages and neutrophils ?

A

Professional phagocytes

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23
Q

What is a macrophage alone ?

A

An antigen presenting cell

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24
Q

What is the neutrophil marker ?

A

Gr1

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25
What is the structure of a neutrophil ?
Multi-lobed nucleus, granular cytoplasm
26
What is a neutrophil derived from ?
Common myeloid progenitors via the myeloblast
27
Where are neutrophils common ?
Blood
28
What are the first cells recruited to tissue ?
Neutrophils
29
What does phagocytosis lead to with neutrophils ?
Fusions with granules, degranulation leads to death
30
What are the markers of a macrophage ?
CD11b, CD14, F4/80, CD68
31
What is the structure of a macrophage ?
Round nucleus, irregular shape/cytoskeleton
32
What is a macrophage derievd from ?
Common myeloid progenitor via monocyte
33
What are the functions of macrophages ?
1. Patrolling/tissue resient macrophages 2. Recruited to site of infection later
34
What does macrophage phagocytosis lead to ?
Lysosomal maturation which liberates antigens
35
What do the signaling functions of the macrophage do ?
Drive inflammation and adaptive immunity
36
What is phagocytosis ?
Highly regulated cellular process involving multiple proteins, rearrangements of actin cytoskeleton
37
What are the other processes that phagocytosis is linked to ?
Antigen processing and initiation of proinflammatory signaling and metabolism
38
Why do cells express receptors ?
To identify common patterns of infection and regulate inflammatory processes
39
What are some jobs that families of PRR may do ?
1. Some trigger phagocytosis uptake 2. Some trigger pro-inflammatory signaling and transcription of cytokine genes 3. Some trigger intracellular maturation and trafficking of cytokine
40
What are the Phagocytic receptors ?
1. C-type lectin receptors 2. Mannose receptors 3. Scavenger receptors 4. Complement receptors
41
What are c-type lectin receptors ?
Dectin-1 recognises zymosan from fungi
42
What are mannose receptors ?
Thought to recognise sugars on bacterial surface and trigger uptake, also play a role in resolution phase of inflammation
43
What are scavenger receptors ?
MARCO, SRA, SRB-1, CD36 bind various glycoproteins from bacteria and fungi as well as host DAMPs
44
What are complement receptors ?
CR3 binds fungal B-glucans and triggers uptake
45
What does the phagosome generally fuse with ?
The lysosome to form the phagolysosome
46
What does the phagosome fuse with in the neutrophil ?
Primary and secondary granules
47
What does the fusion of phagosomes with granules mediate ?
Destruction of pathogen
48
What is autophagy
A process whereby the cell captures and targets cytoplasmic compartments for degradation or can target intracellular microbes
49
What distinguishes autophagy from regular phagocytosis ?
The formation of intracellular double membrane organelles
50
What is the intracellular pathogen in autophagy ?
Ubiquitinated
51
What does the ubiquitinated intracellular pathogen lead to ?
Formation of double membrane autophagosome
52
What mediates te formation of the double membrane autophagosome ?
p62
53
What does the ubiquitinated recruit ?
autophagosome systems - using Atf5 and LC3 systems
54
What is the macrophage and neutrophil products by acidification ?
Bacteriostatic or bacteriacidal
55
Wha are the macrophage and neutrophil products by toxix oxygen products ?
1. Superoxide Oygen 2. Hydrogen peroxide 3. Single oxygen 4. Hydroxyl radical 5. Hypohalite
56
What are the macrophage and neutrophil producrs of toxic nitrohen oxides ?
Nitrogen oxide
57
What are the macrophage products of antimicrobial peptides ?
1. Cathelicidin 2. Macrophage elastase derived peptides
58
What are the neutrophil prducts of antimicrobial peptides ?
1. Alpha defensis 2. Beta defensins HBD4 3. Cathelicidin 4. Azurocidin 5. Bacterial permeability inducing protein 6. Lactoferrin
59
What are the macrophage and neutrophil products in enzymes ?
1. Lysosymes 2. Acid hydrolases
60
What are the competitiors of macrophage and neutrophil products ?
1. Lactoferrin 2. Vitamin B12 binding protein
61
How do cells make NADPH ?
Pentose phosphate pathway during glycolysis
62
In the respiratory burst was is inactive in resting cells ?
NADPH oxidase
63
What is chronic granulomatous disease ?
Deficiency in NAADPH oxidase
64
What does effecrocytosis involve ?
1. Recognition of dead and dying cells 2. Uptake and internalisation 3. Digestion of dead cell and associated pathogen 4. Induction of anti-inflammatory response
65
What type of macrophages are more pro-inflammatory ?
M1
66
What type of macrophagess are anti-inflammatory ?
M2
67
How do we know which macrophage is to be sent ?
1. Extra cellular signals 2. Cytokines produced in the environment
68
How are M1 and M2 distinguished ?
By arginine use
69
What does each type of macorphage do ?
1. Express unique markers 2. Prouce unique cytokine 3. Drive different T cell responses 4. Has unique metabolic profiles
70
What does M1 express ?
iNOS
71
What does M2 express and use ?
Arginase-1
72
What is the monocyte called in the bone marrow ?
monoblast
73
What is the monocyte in the circulation called ?
Monocyte
74
What is the monocyte in the tissue called ?
Macrophage
75
What is the inflammatory monocyte in the circulation called ?
GR1+LY6Chi
76
What is the resident/regulatory monocyte in the circulation called ?
GR1-LY6Clow
77
What initiates inflammatory response ?
Tissue/Patrolling macrophages
78
Where are tissue/patrolling macrophages found?
Mucosal surfaces
79
What is the resident macrophage in the brain ?
microglia
80
What is the resident macrophage in the liver
Kuppfer cells
81
What is the resident macrophage in the lung
Alveolar macrophages
82
What is the resident macrophage in the gut
Intestinal macrophage
83
What is the resident macrophage in the skin
Langerhans cells
84
What is the resident macrophage in the bone
osteoclast
85
What are the common functions of tissue resident macrophages ?
1. Regulate homeostasis 2. Repair and recycling

Core Concepts in Immunology (22 decks)

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