Innate Immune Cells Flashcards

1
Q

What has the immune system evolved to do?

A
  • to sculpt colonization to benefit the host
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2
Q

How do single-celled organisms fight microbes?

A
  • by harnessing toxic peptides to thwart invading microbes

- this mechanism is still found in complex animals

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3
Q

How have multicellular organisms evolved their immune system to fight invaders?

A
  • they devote specialized cells to engulf bacteria and viruses
  • evolved from nutritive phagocytes in gutless animals
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4
Q

How have higher vertebrates evolved their immune system to fight invaders?

A
  • the big bang of immunology
  • evolved second form/ adaptive immunity where specialized WBC exquistely target a specific pathogen and maintain the body as an immune memory
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5
Q

What does immediate innate, early induced innate and adaptive immune response all have in common?

A
  • they all have the same end goal to remove the infectious agent
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6
Q

What cells are in innate immunity?

A
  • macrophage
  • dendritic cell
  • mast cell
  • NK cell
  • complement protein
  • neutrophil, eosinophil, basophil (grouped together into granulocytes)
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7
Q

What cells are in adaptive immunity?

A
  • B-cell
  • T-cell
  • antibodies
  • CD4+ T cell
  • CD8+ T cell
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8
Q

What cells are in both innate and adaptive immunity?

A
  • y T cell

- NK cell

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9
Q

Where do pluripotent hematopoietic stem cells live?

A
  • in the bone marrow
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10
Q

T/F: there are a lot of pluripotent hematopoitic stem cells

A
  • False

- there’s a small number in the body, but they’re self-renewing, so any amount is good because they can regenerate

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11
Q

What do pluripotenet hematopoietic stem cells respond to?

A
  • stromal cells, cytokines, colony stimulating factors (CSF)
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12
Q

What are the lineage development and cell diferentiation of pluripotent hematopoietic stem cells mediated by?

A
  • coordinated and regulated expression of transcription factors
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13
Q

What’s the cellular lifespan of red blood cells?

A

120 days

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14
Q

What’s the lifespan of T-cells?

A

30 years

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15
Q

What’s the lifespan of neutrophils?

A

1-2 days

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16
Q

T/F: normally hematopoiesis is steady state but can increase 10-20 fold in hemorrhage or infection

A
  • True
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17
Q

What are the 5 colony stimulating factors?

A
  • IL-3 (used to be multi-CSF)
  • Macrophage-CSF (M-CSF)
  • Granulocyte-CSF (G-CSF
  • Granulocyte-macrophage- CSF (GM-CSF)
  • Erythropoietin (EPO)
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18
Q

T/F: the environment cannot affect the innate immune system

A

False, it can affect the regulation of different cells

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19
Q

Can cells going through different stages of differentiation able to give rise to all blood cell types?

A
  • no, they can still make multiple cell types but are no longer able to differentiate into all types of blood cells
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20
Q

What are the intermediate stages referred to as?

A
  • common progenitor cells
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21
Q

T/F: pluripotent hematopoietic stem cells do not directly differentiate into immune cells

A

True, they have to pass through different stages of differentiation

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22
Q

What’s the dependent lineage from transcription factor GATA-1?

A
  • erythroid
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23
Q

What’s the dependent lineage from transcription factor GATA-2?

A
  • erythroid
  • myeloid
  • lymphoid
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24
Q

What’s the dependent lineage from transcription factor PU-1?

A
  • erythroid (maturation)
  • myeloid (late stages)
  • lymphoid
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25
Q

What’s the dependent lineage from transcription factor Bmi-1?

A
  • all lineages
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26
Q

What’s the dependent lineage from transcription factor Ikaros?

A
  • lymphoid
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27
Q

The transition between various stages of differentiation is driven by what?

A
  • exposure to cytokines, including CSFs
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28
Q

What does the activity of the transcription factor induce?

A
  • all developmental changes involved in cell differentiation
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29
Q

T/F: neutophils, basophils, lymphocytes and eosinophils look very similar

A

False, they look very different

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30
Q

What’s the activated function of macrophages?

A
  • phagocytosis and activation of bactericidal mechanisms

- antigen presentation

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31
Q

What’s the activated function of dendritic cells?

A
  • antigen uptake in peripheral sites

- anitgen presentation

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32
Q

What’s the activated function of neutrophils?

A
  • phagocytosis and activation of bactericidal mechanisms
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33
Q

What’s the activated function of eosinophils?

A
  • killing of antibody-coated parasites
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34
Q

What’s the activated function of basophils?

A
  • promotion of allergic responses and augmentation of anti-parasitic immunity
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35
Q

What’s the activated function of mast cells?

A
  • release of granuoles containing histamine and active agents
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36
Q

T/F: monocytes can give rise to phagocytes

A
  • true
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37
Q

Where are monocytes present?

A
  • in the blood where they traffic to various tissues
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38
Q

When does the monocyte differentiate? What does it Differentiate into?

A
  • once it enters a tissue the monocyte differentiates into a macrophage
  • named according to tissue
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39
Q

Is monocyte differentiation specific?

A
  • it’s very organ specific so it can fight off invaders
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40
Q

How much do monocytes account for in every organ in the body?

A
  • 10-15%
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41
Q

What is the name of the macrophage/monocyte that captures and kills pathogens through phagocytosis?

A
  • mononuclear phagocytes
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42
Q

What is the name of the macrophage/monocyte that processes and presents pathogen molecules to the T-cells?

A
  • antigen presenting cells (APC)
  • they present pathogen to cells in the adaptive immune system (like TOLLs) so T cells can activate and know how to attack
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43
Q

T/F: monocytes/macrophzges are 1st class of phagocytes

A

True

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44
Q

What’s the difference between monocytes and macrophages physically?

A
  • macrophages have more lysosomes, phagosomes and pseudopodia (things sticking out)
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45
Q

What are the 5 changes that occur in a monocyte when it differentiates into a macrophage?

A
  • enlarges 5-10x
  • increases intracellular organelles
  • increases phagocytic ability
  • increased amount of hydrolytic enzymes
  • begin to secrete a variety of soluble factors
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46
Q

T/F: macrophages serve the same functions in different tissues

A

False, macrophages serve different functions in different tissues

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47
Q

What are the 4 things macrophages do?

A
  • detect pathogens (PRRs)
  • clear infection (phagocytosis)
  • activate adaptive immune system (MHC-T cells)
  • shape/direct adaptive immune response (cytokines)
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48
Q

What are the receptors on macrophages?

A
  • LPS receptor CD14
  • Toll-like receptors (TLR)
  • Fc receptors
  • mannose receptor
  • complement receptors
  • IFNg receptor
  • Chemokine receptors
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49
Q

How do macrophages clear infections through direct clearance?

A
  • phagocytosis of pathogen, killing it
50
Q

How do macrophages clear infections through enhanced inflammatory response?

A
  • contain/isolate pathogen
  • secrete cytokines
    raise body temperature
  • recruit additional cells (neutrophils)
51
Q

What are the 2 methods macrophages use to clear infections?

A
  • direct clearance

- enhance inflammatory response

52
Q

Where are dendritic cells located?

A
  • skin
53
Q

Do dendritic cells move?

A
  • no they’re stationary
54
Q

What do dendritic cells look like?

A
  • unusually shaped phagocytic cells with long, spindly membrance processes
55
Q

What do dendrtic cells (DC) express high levels of?

A
  • MHCII
56
Q

Why do DC express high levels of MHCII?

A
  • DC are antigen presenting cells (like macrophages) and these high levels allow the cell-surface molecule to present the pathogens to the CD4+ T-cells
57
Q

T/F: DC are most important cell type for the activation of naive T-cells

A

True

58
Q

Where do dendritic cells develop?

A
  • there are many different types of DC so different areas
  • subset from lymphoid lineage
  • subset from myeloid lineage
59
Q

What are non-lymphoid dendritic cells called?

A
  • depends on where it is in the body
  • skin - Langerhans
  • other organs - interstitial dendritic cells
60
Q

What happens if a dendritic cell encounters a pathogen?

A
  • after it picks it up in the tissue the DC will change its morphology in the blood and lymph to be veiled
  • moves to lymph node
61
Q

What do lymphoid dendritic cells called?

A
  • depends on here it is in the body
  • interdigitating DCs in T-cell rich organ sites
  • follicular DCs in B-cell rich lymphoid organ site
62
Q

How do Langerhans cells drain into the lymph node?

A

1) antigen uptake by Langerhans cells in the skin

2) Langerhans cells leave the skin and enter the lymphatic system

63
Q

How do dendritic cells drain into the lymph node?

A

1) mature dendritic cells enter the lymph node from infected tissues and can transfer some antigens to resident dendritic cells
2) B7-positive dendritic cells stimulate naive T cells

64
Q

How many functions do dendritic cells serve?

A
  • one, they just want to pick up pathogens and take them to the lymph node
65
Q

What are a couple physical features of neutrophils?

A
  • lots of granules, have a primary and secondary granule

- odd shaped nucleus, like a U

66
Q

What’s a metaphor for neutrophils?

A
  • they’re like the front line horsemen of the innnate immune system
67
Q

How long do neutrophils live for?

A
  • relatively short-lived
  • about 1-2 days and die naturally
  • if they fight something then only hours
    :’’(
68
Q

Where do neutrophils live?

A
  • in the blood
69
Q

Where are neutrophils recruited from?

A
  • from the blood vessels into the infected tissues
70
Q

T/F: neutrophils are voracious phagocytes

A
  • true

- they eat and digest invaders

71
Q

What does polymorphonucelar cells (PMNs)?

A
  • multiobed nucleus

- always refers to neutrophils

72
Q

Are neutrophils granulocytes?

A
  • yes

- they contain a lot of pre-synthesized effector molecules that are stored in granules

73
Q

What happens during neutrophil extravasation?

A

1) endothelial activation
2) tethering and rolling
3) firm adhesion
4) tranmigration and chemotaxis
- goes from round to pancake shape

74
Q

What are the 5 effector mechanisms used by neutrophils?

A
  • phagocytosis
  • degranulation
  • oxidative burst
  • cytokines
  • NETs
75
Q

Define phagocytosis

A
  • eat the infecting pathogen
76
Q

Define degranulation

A
  • dump cytotoxic granular contents on the target
77
Q

Define oxidative burst

A
  • generation of reactive oxygen species (ROS) and reactive nitrogen species (NOS) that can be used to make hydrogen peroxide and hypochloric acid which is toxic to bacteria
78
Q

Define cytokines

A
  • inflammation, activation of other cells
79
Q

Define NETs

A
  • Neutrophil Extracellular Traps

- cell pokes out its own DNA to capture and contain bacteria

80
Q

What are the thress types of granules in neutrophils?

A
  • azurophilic (primary)
  • specific (secondary)
  • gelatinase (tertiary)
81
Q

What makes granules a great risk for collateral damage?

A
  • the granules in neutrophils can either fuse with the phagosome or it can be released into the extracellular environment (i think this is the dangerous part)
82
Q

How long is the life span of neutrophils?

A
  • once fully mature 1-2 days
83
Q

What are the stages of formation for neutophils?

A

1) myeloblast
2) promyelocyte
3) myelocyte
4) metemyelocyte
5) band cell
6) PMN

84
Q

How can a neutrophil suicide be useful?

A
  • by killing themselves they release the contents of their nuclei and mitochondrial DNA
  • the nucleic acid + bactericidal enzymes makes a lethal network outside the cell to trap and kill bacteria
85
Q

What are some physical features of eosinophils?

A
  • lots of granules

- contains large red-staining granules

86
Q

What specific type of infection are eosinophils primarily used for?

A
  • parasitic infections

- the number of eosinophils increase to 10-20% of blood leukocytes during a parasitic infection

87
Q

How is the recognition of parasites enhanced?

A
  • by the addition of an antibody to an eosinophil
88
Q

What are some physical features of basophils?

A
  • lots of large granules
  • horse-shoe shaped nucleus
  • lobed nucleus and heaily granulated cytoplasm
89
Q

What reactions are basophils primarily used in?

A
  • allergic responses

- antiparasitic immunity

90
Q

T/F: basophils are phagocytes

A
  • False

- they aren’t phagocytes

91
Q

How do basophils attack invaders?

A
  • they aren’t phagocytes so instead release large amount of pharamacologically active compunds from in their granules
92
Q

What are basophils important mediators for?

A
  • hypersensitivity

- allergic responses

93
Q

What are some physical features of mast cells?

A
  • normal nucleus

- large granules

94
Q

What activates mast cells?

A
  • IgE
  • bacterial products
  • parasites
95
Q

What are mast cells coated with? How does this help them?

A
  • IgE

- the cell can bind with up to 200 different IgE to its surface

96
Q

What’s a granule content in mast cells?

A
  • neurotransmitters that regulate blood vessel tone
97
Q

What are mast cells known for?

A
  • fighting infections

- ability to cause allergies

98
Q

Where do mast cells differentiate?

A
  • in the tissue

- phenotype varies on location

99
Q

Where are mast cells located?

A
  • at host-environment interfaces

- skin, lungs, gut

100
Q

How involved are mast cells in immune responses?

A
  • very involved

- they’re responsible for telling other cell types to make aware that something is happening and they need to help

101
Q

T/F: natural killer cells are clonal

A
  • False, they are not clonal
102
Q

Are NK cells more responsive to bacterial or viral invaders?

A
  • viral

- other cells are primarily bacterial

103
Q

Do NK cells have markers for B or T-cells?

A
  • no
104
Q

Why are NK cells names natural killer cells?

A
  • they can kill target cells without prior immunization
105
Q

How are NK cells regulated?

A
  • by a balance of activating and inhibiting receptors
106
Q

How do NK cells recognize targets?

A
  • they can recognize targets labeled with antibody

- known as antibody-dependent cellular cytotoxity (ADCC)

107
Q

What is the negative feedback loop seen in NK cells?

A
  • MHC class I on normal cells is recognized by inhibitory receptors that inhibit signals from activating receptors
  • NK cell does not kill the normal cell
108
Q

When would a NK cell kill another cell?

A
  • altered or absent MHC class I cannot stimulate a negative signal, the NK cell is triggered by signals from activating receptors
  • activated NK cell releases granule content, inducing apoptosis in the target cell
109
Q

T/F: NK cells are readily potent helpers available to fight against virus

A

True

110
Q

What is the endothelium?

A
  • a single cell layer that forms continuous lining to contain the blood
111
Q

What are 3 things the endothelium is important for?

A
  • plays critical role in homeostasis
  • it’s a barrier
  • it’s responsive to many mediators
112
Q

How does the endothelium help maintain homeostasis?

A
  • helps maintain coagulation and vascular tone (aka blood pressure)`
113
Q

How does the endothelium act as a barrier?

A
  • it regulates the movement of both fluids and macromolecules and leukocytes
114
Q

How is the endothelium responsive to mediators?

A
  • can actively engage in recruitment of different cells
115
Q

When the endothelial cells are activated what can they do?

A
  • produce oxidants, lipid mediators, cytokines, NO
  • promote coagulation and regulate vascular tone
  • increase microvascular permeability
  • express adhesion and activation molecule resulting in increased leukocytes recruitment
116
Q

Where are platelets derived from?

A
  • bone marrow

- megakaryocyte “bits”

117
Q

Do platelets have a nucleus? Granules?

A
  • no nucleus but lots of granules
118
Q

What are 2 major responses platelets are responsible for for?

A
  • homeostasis (critical)

- inflammation (participates)

119
Q

Do platelets bind to neutrophils or can neutrophils adhere to platelets?

A
  • both!
120
Q

How deos removing platelets affect inflammation?

A
  • it can reduce the inflammatory response
121
Q

What do platelets help the body with?

A
  • helps to shield the body from infections

- can enhance the effector function of other cells (NET production by neutrophils)