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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
Q

What is the structure of a neutrophil ?

A

Multi-lobed nucleus, granular cytoplasm

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26
Q

What is a neutrophil derived from ?

A

Common myeloid progenitors via the myeloblast

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27
Q

Where are neutrophils common ?

A

Blood

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28
Q

What are the first cells recruited to tissue ?

A

Neutrophils

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29
Q

What does phagocytosis lead to with neutrophils ?

A

Fusions with granules, degranulation leads to death

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30
Q

What are the markers of a macrophage ?

A

CD11b, CD14, F4/80, CD68

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31
Q

What is the structure of a macrophage ?

A

Round nucleus, irregular shape/cytoskeleton

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32
Q

What is a macrophage derievd from ?

A

Common myeloid progenitor via monocyte

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33
Q

What are the functions of macrophages ?

A
  1. Patrolling/tissue resient macrophages
  2. Recruited to site of infection later
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34
Q

What does macrophage phagocytosis lead to ?

A

Lysosomal maturation which liberates antigens

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35
Q

What do the signaling functions of the macrophage do ?

A

Drive inflammation and adaptive immunity

36
Q

What is phagocytosis ?

A

Highly regulated cellular process involving multiple proteins, rearrangements of actin cytoskeleton

37
Q

What are the other processes that phagocytosis is linked to ?

A

Antigen processing and initiation of proinflammatory signaling and metabolism

38
Q

Why do cells express receptors ?

A

To identify common patterns of infection and regulate inflammatory processes

39
Q

What are some jobs that families of PRR may do ?

A
  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
Q

What are the Phagocytic receptors ?

A
  1. C-type lectin receptors
  2. Mannose receptors
  3. Scavenger receptors
  4. Complement receptors
41
Q

What are c-type lectin receptors ?

A

Dectin-1 recognises zymosan from fungi

42
Q

What are mannose receptors ?

A

Thought to recognise sugars on bacterial surface and trigger uptake, also play a role in resolution phase of inflammation

43
Q

What are scavenger receptors ?

A

MARCO, SRA, SRB-1, CD36 bind various glycoproteins from bacteria and fungi as well as host DAMPs

44
Q

What are complement receptors ?

A

CR3 binds fungal B-glucans and triggers uptake

45
Q

What does the phagosome generally fuse with ?

A

The lysosome to form the phagolysosome

46
Q

What does the phagosome fuse with in the neutrophil ?

A

Primary and secondary granules

47
Q

What does the fusion of phagosomes with granules mediate ?

A

Destruction of pathogen

48
Q

What is autophagy

A

A process whereby the cell captures and targets cytoplasmic compartments for degradation or can target intracellular microbes

49
Q

What distinguishes autophagy from regular phagocytosis ?

A

The formation of intracellular double membrane organelles

50
Q

What is the intracellular pathogen in autophagy ?

A

Ubiquitinated

51
Q

What does the ubiquitinated intracellular pathogen lead to ?

A

Formation of double membrane autophagosome

52
Q

What mediates te formation of the double membrane autophagosome ?

A

p62

53
Q

What does the ubiquitinated recruit ?

A

autophagosome systems - using Atf5 and LC3 systems

54
Q

What is the macrophage and neutrophil products by acidification ?

A

Bacteriostatic or bacteriacidal

55
Q

Wha are the macrophage and neutrophil products by toxix oxygen products ?

A
  1. Superoxide Oygen
  2. Hydrogen peroxide
  3. Single oxygen
  4. Hydroxyl radical
  5. Hypohalite
56
Q

What are the macrophage and neutrophil producrs of toxic nitrohen oxides ?

A

Nitrogen oxide

57
Q

What are the macrophage products of antimicrobial peptides ?

A
  1. Cathelicidin
  2. Macrophage elastase derived peptides
58
Q

What are the neutrophil prducts of antimicrobial peptides ?

A
  1. Alpha defensis
  2. Beta defensins HBD4
  3. Cathelicidin
  4. Azurocidin
  5. Bacterial permeability inducing protein
  6. Lactoferrin
59
Q

What are the macrophage and neutrophil products in enzymes ?

A
  1. Lysosymes
  2. Acid hydrolases
60
Q

What are the competitiors of macrophage and neutrophil products ?

A
  1. Lactoferrin
  2. Vitamin B12 binding protein
61
Q

How do cells make NADPH ?

A

Pentose phosphate pathway during glycolysis

62
Q

In the respiratory burst was is inactive in resting cells ?

A

NADPH oxidase

63
Q

What is chronic granulomatous disease ?

A

Deficiency in NAADPH oxidase

64
Q

What does effecrocytosis involve ?

A
  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
Q

What type of macrophages are more pro-inflammatory ?

A

M1

66
Q

What type of macrophagess are anti-inflammatory ?

A

M2

67
Q

How do we know which macrophage is to be sent ?

A
  1. Extra cellular signals
  2. Cytokines produced in the environment
68
Q

How are M1 and M2 distinguished ?

A

By arginine use

69
Q

What does each type of macorphage do ?

A
  1. Express unique markers
  2. Prouce unique cytokine
  3. Drive different T cell responses
  4. Has unique metabolic profiles
70
Q

What does M1 express ?

A

iNOS

71
Q

What does M2 express and use ?

A

Arginase-1

72
Q

What is the monocyte called in the bone marrow ?

A

monoblast

73
Q

What is the monocyte in the circulation called ?

A

Monocyte

74
Q

What is the monocyte in the tissue called ?

A

Macrophage

75
Q

What is the inflammatory monocyte in the circulation called ?

A

GR1+LY6Chi

76
Q

What is the resident/regulatory monocyte in the circulation called ?

A

GR1-LY6Clow

77
Q

What initiates inflammatory response ?

A

Tissue/Patrolling macrophages

78
Q

Where are tissue/patrolling macrophages found?

A

Mucosal surfaces

79
Q

What is the resident macrophage in the brain ?

A

microglia

80
Q

What is the resident macrophage in the liver

A

Kuppfer cells

81
Q

What is the resident macrophage in the lung

A

Alveolar macrophages

82
Q

What is the resident macrophage in the gut

A

Intestinal macrophage

83
Q

What is the resident macrophage in the skin

A

Langerhans cells

84
Q

What is the resident macrophage in the bone

A

osteoclast

85
Q

What are the common functions of tissue resident macrophages ?

A
  1. Regulate homeostasis
  2. Repair and recycling

Core Concepts in Immunology (22 decks)

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