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Innate Immunity > Monocytes and macrophages > Flashcards

Monocytes and macrophages Flashcards

1
Q

Monocyte nucleus shape

A

Bean-shape

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2
Q

Blood concentration

A

10% of circulating cells

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3
Q

Development of monocytes

A

Begin as hematopoietic cells
To common myeloid progenitor (CMP)
To granulocyte/monocyte progenitor
and finally differentiate into monocyte progenitor.

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4
Q

Classical Monocytes

A

CD14+ CD16-, typically CCR2+.

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5
Q

Intermediate Monocytes:

A

CD14+ CD16+, commonly CCR5+.

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6
Q

Patrolling/Non-Classical Monocytes

A

CD14low CD16+, express CX3CR1+ and CD64+.

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7
Q

Mice, Patrolling Monocytes

A

Ly6Clow.

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8
Q

Mice, Classical Monocytes:

A

Ly6Chigh.

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9
Q

Flow Cytometry Markers

A

Utilized to identify and differentiate between various monocyte populations.

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10
Q

Monocyte Role

A

Monocytes perform phagocytosis, present antigens, and secrete cytokines.

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11
Q

Monocyte Migration

A

Can migrate to tissues and transform into macrophages or dendritic cells.

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12
Q

Monocyte maturation

A

Develop from progenitor cells in the bone marrow through various stages before becoming fully mature monocytes.

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13
Q

How long do monocytes circulate in the blood

A

Circulate in the blood for 1-3 days before migrating to tissues.

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14
Q

Surface markers of monocytes

A

CD14,CCR2, CCR5, CX3CR1

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15
Q

CD14 surface marker function

A

A co-receptor for the detection of bacterial lipopolysaccharides (LPS).

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16
Q

CCR2 surface marker function

A

A receptor that mediates chemotaxis toward sites of inflammation.

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17
Q

CCR5 surface marker function

A

Involved in the inflammatory response and may play a role in cell migration and activation.

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18
Q

CX3CR1 surface marker function

A

A receptor involved in adhesion and migration of monocytes.

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19
Q

Monocyte Differentiation into

A

two types of macrophages—M1 (pro-inflammatory) and M2 (anti-inflammatory/healing)

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20
Q

Monocyte and Cancer

A

Ongoing research investigates the role of monocytes in cancer, healing, and as vehicles for drug delivery, human and mouse monocytes serve as models to study immune response and pathology

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21
Q

Balance of M1 and M2

A

The balance between M1 and M2 can influence the outcome of many diseases. (diseases, or hematological disorders.)

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22
Q

High and low monocyte count

A

High monocyte counts can indicate chronic inflammation, while low counts may suggest bone marrow suppression or systemic lupus erythematosus (SLE).

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23
Q

Functions of Non-classical/Patrolling Monocytes

A

Sense tissue damage, involved in tissue repair and angiogenesis.
Scavenge and respond to viruses/nucleic acid via endosomal TLR7/8 with cytokines such as TNF, IL-1β, CCL3.
Scavenge immune complexes and have a role in autoimmunit

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24
Q

how do monocyte scavengers and respond to viruses/nucleic acid

A

via endosomal TLR7/8 with cytokines such as TNF, IL-1β, CCL3.

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25
Q

Functions of Classical Monocytes

A

Exhibit antimicrobial activity through phagocytosis.
Produce reactive oxygen species (ROS), nitric oxide (NO), myeloperoxidase (MPO), and Type I Interferons.
Mediate inflammation and leukocyte recruitment, responding to cytokines like IL-1α, TNF, IL-6, IL-8, and CCL2.
Activate T cells due to the presence of MHC class II on their surface.

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26
Q

What does classic monocytes produce

A

Produce reactive oxygen species (ROS), nitric oxide (NO), myeloperoxidase (MPO), and Type I Interferons.

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27
Q

How do they mediate inflammation and leukocyte recruitment

A

responding to cytokines like IL-1α, TNF, IL-6, IL-8, and CCL2.

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28
Q

TLR4 ligands

A

trigger a response in patrolling monocytes

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29
Q

TLR7/8 ligands

A

prompt a response in classical monocytes.

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30
Q

Ly6C^low and Ly6C^high monocytes have different responses to

A

TLR4 and TLR7/8 stimulation.

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31
Q

monocyte produce key inflammatory cytokines

A

like TNF, IL-1β, and CCL3 during this response.

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32
Q

what do Classical monocytes release

A

They release antimicrobial molecules such as ROS, NO, MPO, and Type I Interferons to neutralize threats.

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33
Q

Classical monocytes function

A

proficient phagocytes that engulf and destroy pathogens and key players in promoting inflammation and recruiting other leukocytes to sites of infection.

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34
Q

Monocyte and MHC II

A

Antigen presentation, and different monocyte subsets respond to various TLRs, which recognize distinct pathogen-associated molecular patterns.

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35
Q

TLR4

A

induces a pro-inflammatory reaction in patrolling monocytes.

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36
Q

TLR7/8

A

Detects viral RNA within endosomes.

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37
Q

What are the stimuli associated with the M1 macrophage phenotype?

A

LPS, IFNγ, TNFα.

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38
Q

What are the biomarkers associated with the M1 macrophage phenotype?

A

TNF, IL-1β, IL-6, IL-12, IL-23, iNOS, COX-2, CCR7

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39
Q

What are the functions associated with the M1 macrophage phenotype?

A

Associated with type 1 inflammation, antigen presentation, and angiogenesis.

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40
Q

What are the stimuli associated with the M2a macrophage phenotype?

A

IL-4, IL-13

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41
Q

What are the biomarkers associated with the M2a macrophage phenotype?

A

TGFβ, arginase-1, Ym1, Fizz1.

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42
Q

What are the functions associated with the M2a macrophage phenotype?

A

with type 2 inflammation, eosinophil recruitment, stabilization of neovascularization.

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43
Q

What are the stimuli associated with the M2b macrophage phenotype?

A

immune complexes, LPS

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44
Q

What are the biomarkers associated with the M2b macrophage phenotype?

A

L-1β, IL-6, CCL1, CXCL1, CCL2

45
Q

What are the stimuli, biomarkers, and functions associated with the M2b macrophage phenotype?

A

antigen presentation, immune regulation.

46
Q

What are the stimuli associated with the M2c macrophage phenotype?

A

IL-10, glucocorticoids, TGFβ1

47
Q

What are the stimuli, biomarkers, and functions associated with the M2c macrophage phenotype?

A

CD163, SOCS3, VEGF, MMP9

48
Q

What are the stimuli, biomarkers, and functions associated with the M2c macrophage phenotype?

A

tissue remodelling, anti-inflammatory properties, and phagocytosis

49
Q

What are the stimuli associated with the M2d macrophage phenotype?

A

TLR agonists, IL-6, A2R agonist, tumor microenvironment

50
Q

What are the biomarkers associated with the M2d macrophage phenotype?

A

VEGF, IL-10, IL-12, NO2.

51
Q

What are the functions associated with the M2d macrophage phenotype?

A

Associated with tumor-associated immune regulation and angiogenesis.

52
Q

Endothelial Activation (for monocyte activation)

A

CD4+ T cells secrete CXCL10; endothelial cells express VCAM1.

53
Q

Recruitment(for monocyte activation)

A

Neutrophils and monocytes migrate to the site.

54
Q

monocyte activation

A

Monocytes differentiate into macrophages, expressing CCR2, CX3CR1, and produce IL-1β, TNFα.

55
Q

Fibroblast ACtivation

A

Driven by IL-13 from CD4+ T cells.

56
Q

Macrophage tissue repair

A

facilitate growth of new tissue and differentiate into M2 phenotype promoting healing.

57
Q

Where do tissue-resident macrophages originate from?

A

originate from embryonic precursors, particularly from the yolk sac and fetal liver monocytes, which migrate to tissues early in development

58
Q

Subtypes of monocytes

A

classical, intermediate, and non-classical/patrolling monocytes, each with distinct surface markers and functions.

59
Q

differentiation Classical monocytes (CD14+ CD16-)

A

migrate through the blood and can differentiate into various macrophage subtypes in tissues.

60
Q

What functions do tissue macrophages serve?

A

phagocytize microbes and dead cells, secrete cytokines that modulate immune responses, present antigens to T cells, and are involved in tissue remodeling and repair.

61
Q

What is the typical size of a monocyte and its nucleus shape?

A

Monocytes are typically 10-15μm in diameter with a characteristic bean-shaped nucleus.

62
Q

What factors differentiate Ly6Clow and Ly6Chigh monocytes in their response to TLR stimulation?

A

Ly6Clow responds differently to TLR4 and TLR7/8 stimulation, with TLR4 inducing a pro-inflammatory response and TLR7/8 making classical monocytes respond.

63
Q

What are the three populations of monocytes in humans and their markers?

A

Classical (CD14+ CD16-), Intermediate (CD14+ CD16+), and Patrolling/Non-classical (CD14low CD16+).

64
Q

Describe the transition of classical monocytes in tissue.

A

Classical monocytes can transition to patrolling monocytes. They are the first to arrive at an injury site and later become CX3CR1 positive, a transition driven by IL-4/IL-10 for repair.

65
Q

What are the two origins of tissue-resident macrophages?

A

Embryonic origin, where macrophages are established prenatally, and bone marrow hematopoiesis, leading to monocyte-derived macrophages.

66
Q

What are DOMs in the context of macrophage function?

A

DOMs refer to Delayed Onset Muscle Soreness, which is associated with the production of pro-inflammatory cytokines by macrophages

67
Q

What are the unique functions of tissue-resident macrophages?

A

What are the unique functions of tissue-resident macrophages?

68
Q

What are Synovial Tissue Macrophages (STMs)

A

STMs are specialized macrophages forming a protective layer in the synovial membrane of joints.

69
Q

Where do STMs arise from

A

fetal hematopoietic stem cells during embryonic development, indicating early specialization.

70
Q

STM function

A

maintain joint homeostasis and prevent autoimmune reactions, act as a crucial barrier to infection and are implicated in the pathogenesis and resolution of arthritis.

71
Q

STMs

A

Synovial Tissue Macrophage

72
Q

Role of Macrophage Polarization in Rheumatoid Arthritis (RA)

A

macrophages can exhibit M1 or M2 polarization, contributing to either inflammation (M1) or healing (M2)

73
Q

M1 in RA

A

pro-inflammatory and often exacerbate the destruction of joint tissue.

74
Q

What does it mean that macrophages are heterogeneous?

A

existence of diverse macrophage subtypes, each with unique functions and phenotypic markers.

74
Q

M2 in RA

A

facilitate tissue repair and regeneration, reducing inflammation.

75
Q

Balance of M1 and M2 in RA

A

influences the progression and resolution of RA symptoms.

76
Q

why is macrophages are heterogeneous essential

A

This plasticity is vital for responding appropriately to various pathological conditions.

77
Q

How do monocyte-derived and tissue-resident macrophages differentiation?

A

Monocyte-derived macrophages can differentiate into tissue-resident macrophages adapting to the needs of the local microenvironment.

78
Q

Tissue-resident macrophages originate from

A

both the embryo and the bone marrow, allowing a combination of innate immune memory and adaptive response.

79
Q

Integration of monocyte-derived and tissue-resident macrophages

A

Coordinated immune response, ranging from initial inflammation to subsequent healing processes.
Their collective activities are crucial in tissue repair, inflammation resolution, and maintenance of tissue homeostasis.

80
Q

How do macrophages assist in the resolution of inflammation

A

secreting anti-inflammatory cytokines and growth factors such as VEGF-A, promoting angiogenesis.

81
Q

How do Tissue repair macrophages help resolve inflammation

A

display receptors like IL-4R and CD206 and can derive from both local proliferation and recruitment of circulating monocytes.

82
Q

What is Macrophage Polarization?

A

dynamic changes in macrophage function in response to environmental cues, resulting in diverse phenotypes: pro-inflammatory (M1) or anti-inflammatory (M2).

83
Q

M1 macrophages are stimulated by

A

LPS and IFNγ, leading to an inflammatory response critical for defense against pathogens.

84
Q

M2 macrophages, induced by

A

IL-4 and IL-13, play roles in tissue repair, immune regulation, and resolution of inflammation.

85
Q

What characterizes pro-inflammatory (M1) macrophages?

A

produce inflammatory cytokines (TNF-α, IL-1β, IL-6), reactive nitrogen and oxygen species, and present antigens to T cells, fueling the inflammatory response.

86
Q

M1 involved in

A

initial defense mechanism against pathogens and are associated with the progression of inflammatory diseases.

87
Q

M1 express

A

high levels of surface molecules like CSF1R and produce enzymes such as iNOS.

88
Q

What characterizes anti-inflammatory (M2) macrophages?

A

contribute to the resolution phase of inflammation, tissue remodeling, and repair, as well as the maintenance of homeostasis.

89
Q

M2 produce

A

anti-inflammatory cytokines like IL-10 and growth factors including TGF-β to facilitate healing.

90
Q

M2 arise from

A

arious signals such as IL-4, IL-13, and immune complexes, influencing their specific roles in the immune response.

91
Q

How do macrophages diversify and specialize?

A

Macrophages exhibit remarkable plasticity, with the ability to switch between M1 and M2 phenotypes depending on the microenvironmental context.

92
Q

Macrophage specialization

A

influenced by factors such as tissue of residence, length of stay in the tissue, and the nature of the inflammatory respons

93
Q

What is TGF-β and its role in the immune system?

A

regulator in wound healing, fibrosis, and immune cell regulation, helping to suppress inflammation and facilitate tissue remodeling.

94
Q

TGF-β

A

Transforming Growth Factor-Beta

95
Q

Function of VEGF in tissue repair?

A

stimulates angiogenesis, the formation of new blood vessels, crucial for supplying nutrients and oxygen to healing tissues.

96
Q

VEGF

A

Vascular Endothelial Growth Factor

97
Q

FGF

A

Fibroblast Growth Factor

98
Q

role of FGF in the healing process?

A

involved in cell proliferation and differentiation during wound healing and tissue regeneration.

99
Q

What does PDGF do in tissue repair?

A

recruits cells like fibroblasts to the injury site to proliferate and produce extracellular matrix, contributing to the repair.

100
Q

PDGF

A

Platelet-Derived Growth Factor

101
Q

How does EGF contribute to tissue regeneration?

A

promotes cell growth and differentiation, especially epithelial cell repair, aiding in the healing of wounds.

102
Q

EGF

A

Epidermal Growth Factor

103
Q

IGF

A

Insulin-Like Growth Factor

104
Q

IGF’s importance in muscle and bone repair?

A

aids in cell survival and growth, playing a key role in muscle and bone repair.

105
Q

Macrophages contribute to tissue repair and regeneration by releasing a variety of growth factors;

A

TGF-β - Transforming Growth Factor-Beta
VEGF - Vascular Endothelial Growth Factor
FGF - Fibroblast Growth Factor
PDGF - Platelet-Derived Growth Factor
EGF - Epidermal Growth Factor
IGF - Insulin-Like Growth Factor

106
Q

Necrotic EC

A

necrotic endothelial cells

107
Q

Necrotic EC

A

death of cells in an organ or tissue due to disease, injury, or failure of the blood supply.

Innate Immunity (9 decks)

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