Exam 1: Dr. Kaplan Inflammation: Mechanisms 2 Flashcards

1
Q

What are the 3 ways on innate immune cell killing?

A

Phagocytosis
Release of antimicrobial products
Targeted destruction of infected host cells

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2
Q

What do the innate immune cell killings defend against?

A

A variety of pathogens without eliciting help from the adaptive system

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3
Q

How quickly can the innate immune cell killing mechanisms be deployed?

A

Immediately without previous exposure, but can continue to work after adaptive immune response has been mounted

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4
Q

What are 3 types of phagocytes?

A

Macrophages
Neutrophils
Dendritic cells

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5
Q

What are the 3 stages of phagocytosis?

A

Recognition and adhesion of particles on plasma membrane of phagocyte
Membrane and cytoskeletal reorganiztion to mediate particle engulfment and creation of a phagosome
Maturation of phagosome to microbicidal and degradative phagolysosome

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6
Q

What are examples of some PRRs?

A

MR/CD206
Dectin-1
Scavenger receptor A1
Phosphatidyl serine receptor

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7
Q

What does MR/CD206 recognize?

A

Mannose and fucose on bacteria, fungi, and viruses

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8
Q

What does dectin-1 recognize?

A

β-glucan residues on fungi

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9
Q

What does scavenger receptor A1 recognize?

A

Polyanionic ligands on various microbes

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10
Q

What does phosphatidyl serine receptor recognize?

A

Phosphatidyl serine on apoptotic cells

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11
Q

What is recognition mediated by?

A

PRRs and opsonic receptors

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12
Q

What is opsonization?

A

Process whereby particles are coated with a protein-binding enhancer to enhance phagocytosis

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13
Q

What are the 2 major opsonins that mammals have?

A

Complement (C3b)

Antibody (IgG)

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14
Q

What can also act as an opsonin when bound to microbes?

A

CRP

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15
Q

What are 2 examples of opsonic receptors?

A

CR3

FCγ1R/CD64

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16
Q

What does CR3 recognize?

A

C3b on an surface bound by C3b

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17
Q

What does FCγ1R/CD64 recognize?

A

The Fc portion of the IgG antibody on any surface bound by IgG

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18
Q

What does the phagocytosis of irregularly shaped microbes or several microbes require?

A

Alteration in morphology

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19
Q

What does recognition of particle by phagocytic receptors result in?

A

Tight adhesion of microbe to phagocyte and clusters the receptors together

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20
Q

How long does the phagosome last?

A

Only a few seconds, but quickly evolves to an acidic, oxidative, degradative, antimicrobial chamber

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21
Q

What does the evolution of the phagolysosome evolution involve?

A

Fusion of the phagosome with endosomes and lysosomes in the cell

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22
Q

What does the phagosome do?

A

Recruits protein complexes that actively pump protons into it, reducing pH

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23
Q

What can the lower pH reduced by the protein complexes recruited by phagosomes do?

A

Kill microbes and activate antimicrobial enzymes that have been delivered to the phagosome

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24
Q

What does a phagosome do in neutrophils?

A

It also fuses with a modified lysosome containing high concentrations of antimicrobial proteins

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25
Q

What is an oxidative or respiratory burst?

A

Assembly of NADPH oxidase on phagosomal membrane

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26
Q

What does NADPH oxidase do?

A

Transfers unpaired electrons from NADPH to molecular oxygen generating superoxide

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27
Q

What is superoxide?

A

Extremely reactive and damaging

Reacts with hydrogen ions to form hydrogen peroxide

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28
Q

What is hydrogen peroxide?

A

A powerful oxidant that can be converted to hydroxyl radicals in presence of ferrous ions, which is damaging to all macromolecules

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29
Q

What can neutrophils make?

A

The antimicrobial enzyme myeloperoxidase

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30
Q

What does myeloperoxidase do?

A

Combines hydrogen peroxide with chloride ion to make hypochlorite ion (bleach)

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31
Q

What are the antimicrobial enzymes, proteases, improtant for?

A

Bridging innate with adaptive immunity

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32
Q

What can the amino acid arginine be converted to?

A

Nitric oxide

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33
Q

Why is nitric oxide important?

A

It is a signaling molecule

34
Q

How is nitric oxide antimicrobial?

A

By reacting with DNA and microbial enzymes

35
Q

What can nitric oxide combine with?

A

Superoxide to form peroxynitrite

36
Q

What is peroxynitrite extremely reactive with?

A

Lipid, DNA, and proteins

37
Q

What does bleach do?

A

Kills bacterium

38
Q

What can nitric oxide cause?

A

Vasodilation

39
Q

What are the 3 reactive oxidative burst products that cause damage to proteins and DNA in the bacterium?

A

Superoxide anion
Hydrogen peroxide
Hydroxyl radical

40
Q

What oxidative compounds do macrophages and neutrophils generate in the phagosome?

A
Reactive oxygen species
Reactive nitrogen intermediates
Reactive hypochlorite (Neutrophils only)
41
Q

What cells do degranulation?

A

Neutrophils and eosinophils

42
Q

What is released in mast cell degranulation?

A

Vasoactive substance

43
Q

What is released in neutrophil and eosinophil degranulation?

A

Cytotoxic and degradative proteins and peptides

44
Q

What does degranulation result in?

A

Injury to surrounding tissue

45
Q

What are eosinophils specialists at?

A

Antiparasite leukocytes

46
Q

Why are eosinophils the early responders to parasites?

A

They are often too big to phagocytose

47
Q

What do eosinophil granules contain?

A

Major basic protein (an anti-helminthic cytotoxin)
Eosinophil cationic protein
Eosinophil-derived neurotoxin
Eosinophil peroxidase

48
Q

What is the eosinophil cationic protein?

A

A pore forming protein that punches holes in cell membranes and/or can digest RNA

49
Q

What can punch holes in the cell membranes?

A

Eosinophils and complement

50
Q

What is the eosinophil-derived neurotoxin?

A

A ribonuclease with antiviral properties

51
Q

What does eosinophil peroxidase do?

A

Facilitates oxidative damage by generating hydrogen peroxide

52
Q

What are neutrophil extracellular traps?

A

Sticky, meshlike substance neutrophils can extrude into extracellular space to which bacteria and yeast stick and are killed

53
Q

What do NETs allow?

A

Immobilization of microbes and protects from surrounding tissue from destruction

54
Q

What are fibers of the NET?

A

Neutrohils own DNA, which results in the death of the neutrophil

55
Q

What do NK cells identify?

A

Potentially infected host cells since some microbes are intracellular and cannot be engulfed, ensnared in a NET, or killed by extracellular release of cytotoxins

56
Q

What are NK cells classified as?

A

Lymphocytes, but do not possess antigen specific receptors

57
Q

What do NK cells express?

A

Several receptors that recognize sick and stressed host cells
Receptors to recognize cells that are not displaying their self markers because they have not been altered by the pathogen

58
Q

What do NK cells kill?

A

Infected or transformed cells

59
Q

What do NK cells serve as?

A

The bridge to adaptive immunity

60
Q

What do NK cell recognize?

A

Receptors on host cells

61
Q

What happens if the receptors on host cells are not expressed?

A

The NK cell will destroy that cell

62
Q

What receptors do NK cells use?

A

Killer lectin-like receptors

Killer cell immunoglobulin-like receptors

63
Q

What do receptor sense?

A

Ligands that indicate abnormality

64
Q

What do NK cell-activating receptors do?

A

Directly detect conserved viral proteins on surface of infected cells
May also detect modified ligands

65
Q

What do all nucleated cells express on the surface?

A

MHC I

66
Q

What do NK cells do with MHC I?

A

Recognize it as an indication of normal function

67
Q

What do inhibitory signals to NK cells do?

A

Override the activating signal from identifying an altered protein

68
Q

What happens once an NK cell encounters a host cell that triggers it activating receptor without triggering its inhibitory receptor?

A

The NK cell will kell the infected/altered cell

69
Q

What is the killing mechanism of NK cells similar to?

A

The killing mechanism of Tc cells

70
Q

What do NK cells release?

A

Lytic granules

71
Q

What is different about the release from NK cells when compared to the release from neutrophils or eosinophils?

A

It is directed

72
Q

What do NK cells form with the target cell?

A

A tight are of adhesion with the target cell (NK immunological synapse)

73
Q

What is the NK immunological synapse?

A

Collection of adhesion molecules carefully arranged by NK cytoskeleton

74
Q

What does the NK immunological synapse act to do?

A

Dock the NK cell with target cell

75
Q

What does the NK immunological synapse form?

A

Tight seal so that granule contents are only released to the target cell

76
Q

What are the cytotoxic molecules associated with the NK immunological synapse?

A

Perforin

Granzyme

77
Q

What does perforin do?

A

Inserts itself into plasma membrane of target cell forming pores

78
Q

What is granzyme?

A

A family of serine proteases that enter via pores made by perforin

79
Q

Why does an NK cell not die as a result of killing a target cell from the release of perforin and granzyme?

A

It is resistant to its own perforin and granzyme

80
Q

What is antibody-dependent cell-mediated cytotoxicity by NK cells?

A

Similar to how antibodies enhance phagocytosis, antibodies can also augment NK cell-mediated cytotoxicity

81
Q

After an adaptive humoral response generates circulating antibodies to the microbe, what can the antibodies do?

A

Attach to a viral or neoplasm-associated antigens on the surface of cells

82
Q

What can NK cells recognize antibody-coated cells with?

A

Their Fc receptors