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05. HDM Test 1 > 3. Innate Immune System > Flashcards

3. Innate Immune System Flashcards

1
Q

What sort of pathogen is poorly affected by inflammation?

A

Intracellular pathogens

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2
Q

What is the downside to inflammation?

A

It can lead to substantial tissue damage and disease

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3
Q

What is a function of the innate immune system that has nothing to do with bacteria?

A

Initiation of the process of tissue repair

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4
Q

What might cause pain at the site of inflammation?

A

Inflammatory mediators released by immune cells stimulate the nerves.

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5
Q

What is the function of type 1 (non-immune) interferon?

A

Blocks viral replication within host cels

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6
Q

What do cells of the innate immune system chiefly recognize?

A

Pathogen associated molecular patterns

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7
Q

What are pathogen associated molecular patterns (PAMPs) unique to?

A

A given class of microbes

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8
Q

Innate immune cells recognize pathogens, so why is it we say they’re less specific than adaptive cells?

A

Since innate cells recognize PAMPs rather than unique antigens, so they are said to be less specific.

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9
Q

What are the four criteria for a pathogen associated molecular pattern to be recognized by our innate immune system?

A
  1. Effective indicator of pathogen
  2. Unique to a class of pathogen
  3. PAMP cannot be easily supressed or hidden by the pathogen (vital to life)
  4. No structural similarity to self antigens
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10
Q

What are the primary PAMPs for:

Gram Negative Bacteria

A

Lipopolysaccaride

Porin

Lipoproteins

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11
Q

What are the primary PAMPs for:

Gram Positive bacteria

A

Peptidoglycan

Lipoteichoic acid

Teichoic acid

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12
Q

What is the primary PAMP for:

Mycobacteria

A

Lipoarabinomannan

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13
Q

What is the primary PAMP for:

Fungi

A

Manno-proteins

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14
Q

What are two important locations for toll like receptors in the cell?

A

On the cell surface and on the inside of endosomes

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15
Q

What do endosomal TLRs respond to?

A

Nucleic acids only

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16
Q

Which four TLRs recognize intracellular pathogens?

A

TLR 3,

TLR 7,

TLR 8,

TLR 9

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17
Q

Why do mannose PRRs not respond to the mannose in our bodies?

A

Because they respond to glycans with terminal mannose only, which does not occur in humans.

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18
Q

For the TLR1:TLR2 heterodimer:

What ligands are recognized?

What cells carry the receptor?

A

Lipopeptides and GPI

Monocytes, dendritic cells, eosinophils, basophils, mast cells

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19
Q

For the TLR2:TLR6 heterodimer:

What ligands are recognized?

What cells carry the receptor?

A

Lipoteichoic acid and Zymosan

Monocytes, dendritic cells, eosinophils, basophils, mast cells

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20
Q

For TLR3

What ligands are recognized?

What cells carry the receptor?

A

Double stranded viral RNA

NK Cells

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21
Q

For the TLR4:TLR4 homodimer:

What ligands are recognized?

What cells carry the receptor?

A

Lipopolysaccaride

Macrophages, dendritic cells, mast cells, eosinophils

(not basophils)

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22
Q

For TLR5

What ligands are recognized?

What cells carry the receptor?

A

Flagellin

Intestinal epithelial cells

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23
Q

For TLR7

What ligands are recognized?

What cells carry the receptor?

A

Single stranded viral RNAs

Plasmacytoid dendritic cells, NK cells, eosinophils, B Cells

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24
Q

For TLR8

What ligands are recognized?

What cells carry the receptor?

A

Single stranded viral RNA

NK cells

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25
Q

For TLR 9

What ligands are recognized?

What cells carry the receptor?

A

Unmethylated CpG-rich DNA

Plasmacytoid dendritic cells, B cells, eosinophils, basophils

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26
Q

What dimers can TLR 10 form?

A

TLR10:TLR10 homodimer

TLR10:TLR1 heterodimer

TLR10:TLR2 heterodimer

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27
Q

Why is NF-κB so important in immunology?

A

It is a pan-inflammatory transcription factor

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28
Q

What adaptor protein does TLRs 1, 2, 5, 6, 7, 8, and 9 (not 3, 4, 10) use to activate NF-κB and IRF?

A

MyD88

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29
Q

What adaptor protein does TLR 3 use to activate NF-κB and IRF

A

TRIF

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30
Q

What adaptor protiens does TLR4 use to activate NF-κB and IRFs?

A

MyD88 and TRIF

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31
Q

What TLRs are used for fungi?

A

TLRs 2, 6

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32
Q

What TLRs are used against bacteria?

A

TLRs 1, 2, 4, 5, 9

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33
Q

What TLR’s are used against viruses?

A

TLRs 3, 7, 8, 9

(these are the endosomal TLRs)

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34
Q

What are the six steps from TLR 4 to NF-κB?

A

TLR4 binds MyD88

MyD88 activates IRAK

IRAK activates TRAF6

TRAF6 activates IKK

IKK activates IκB

IκB degrades, releasing NF-κB

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35
Q

What generates damage associated molecular patterns?

A

Necrosis

(Apoptosis does not)

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36
Q

What particular cells detect damage associated molecular patterns?

A

Dendritic cells

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37
Q

What is HMGB1

What is its receptor?

A

A DAMP released passively during necrosis

RAGE is the receptor

38
Q

What are the three DAMPs discussed in class?

A

HMGB1 (High Mobility Group Box 1)

Uric Acid

HSPs (Heat Shock Protien)

39
Q

What is the common transcription factor for DAMP and PAMP response?

A

NF-κB

40
Q

What is the function of Nod Like Receptors (NLRs)?

A

They are a family of cytosolic receptors that sense PAMPs and DAMPs in the cytoplasm

41
Q

What is the primary function of the inflammasome?

A

Activation of caspase 1

42
Q

What is the main function of caspase 1?

A

Activation (via cleavage) of IL-1beta and IL-18 to drive inflammation and fever

43
Q

What are the three members of the scavenger receptor family?

A

SR Class A Type I

SR Class A Type II

MARCO

44
Q

What domain is missing from SR Class A type II, but is present in the other two types?

A

SR Cystine Rich domain (SRCR)

45
Q

What domain is missing in MARCO scavenger receptors, but is present in the other two SRs?

A

Alpha Helical coiled coil domain

46
Q

What domain is common among all three scavenger receptors?

A

Collagen like domain

47
Q

How to scavenger receptors recognize bacteria to encourage phagocytosis?

A

Through the negative charges present on bacterial lipopolysaccharide, lipoteichoic acid, nucleic acids, beta-glucan, and protiens.

48
Q

Generally speaking, what are bound by the lectin family of Pattern Recognition Receptors?

A

Carbohydrates

49
Q

What important immune function is associated with soluable Mannose Binding Lectin (MBP)?

A

Compliment activation

50
Q

What lectin receptor subset is present on macrophages and, in soluable form, in blood?

A

Mannose receptors

51
Q

What are cathelicidins?

A

Antimicrobial peptides produced by neutrophils and the epithelial cells in the skin, GI and respiratory tract.

52
Q

What three mechanisms would an activated neutrophil undergo to control bacterial growth?

A

Respiratory Burst

Release of Granules

Phagocytosis

53
Q

What can macrophages do that neutrophils don’t usually do?

A

Release inflammatory mediators and present antigens

54
Q

What is the special function of eosinophils?

A

Combat helminthes and multicellular parasites through the use of cationic granules

55
Q

What do natural killer cells use to kill infected host cells?

A

The cytolytic mediator perforin and granzymes

56
Q

How do granzymes kill a cell?

A

They force the cell into apoptosis

57
Q

Why is N-Formylmethionyl peptide important to macrophages?

A

It exists in prokaryotes, but not in eukaryotes. Macrophages use it to help determine self vs non-self.

58
Q

What reaction is incited by a TLR in a phagocyte?

A

Production of cytokines and reactive oxygen intermediates (ROIs) which leads to phagocytosis of the offending organism

59
Q

What mechanism to dendritic cells use to acquire antigens for presentation?

A

Receptor mediated endocytosis and pinocytosis

Not phagocytosis

60
Q

Where do classical (myeloid) dendritic cells reside?

A

Skin, mucosa, and organ parenchyma

61
Q

To what cells are antigens displayed by dendritic cells?

A

T Cells

62
Q

What is the primary function of plasmacytoid dendritic cells?

A

Antiviral functions relating to the production of interferon 1

63
Q

Where will you not be able to find mature mast cells?

A

In the blood. Mature mast cells are only found in the tissues

64
Q

Why are natural killer cells less likely to kill a cell that is producing lots of MHC 1?

A

MHC 1 inhibits NK activity

65
Q

What are NK cell’s activating receptors called?

A

Killer cell immunoglobulin like receptors (KIRs)

66
Q

What is activated by NK cell activating receptors (killer cell immunoglobulin like receptors, KIR’s)?

A

Protein Tyrosine Kinase

67
Q

What do natural killer cells produce to signal macrophages that a potentially infected cell is about to apoptose?

A

Interferon gamma

68
Q

What are the three paths to activate compliment?

A

Alternative pathway

Classical Pathway

Lectin Pathway

69
Q

What is the intersection point for the three pathways of compliment activation?

A

Production of C3b

70
Q

What initiates the classical pathway?

A

Binding of IgM or two IgG’s on the microbial surface.

71
Q

What are the unique steps of the classical pathway of compliment activation?

(Starts with C1 and goes to C3b)

A

C1 is activated by IgM or 2x IgG

C1 cleaves C2 and C4 into a and b domains

C4b binds to the bacterial surface and C2a binds to C4b.

C2a:C4b functions as a C3 convertase, cleaving C3 and forming C3b

72
Q

In the classical pathway, what forms the C5 convertase?

A

C2a, C4b, C3b

73
Q

What are the functions of the products of the C5 convertase?

A

C5a (anaphylatoxin): potent mediator of inflammation

C5b: initiates MAC attack

74
Q

What are the four functions of the compliment system?

A

Lysis of foreign cells and bacteria (MAC)

Opsonization (C3b, C3bi)

Vasodilation (C3a, C4a, C5a)

Clearance of immune complexes (C3a, C3b - absence leads to autoimmune disease)

75
Q

What is the function of acute phase protiens?

A

Initiation of systemic inflammation

76
Q

What organ produces acute phase proteins, and what signaling molecule regulates their production?

A

Liver hepatocytes produce acute phase protiens in response to IL-6 mostly, and to a lesser extent, TNF and IL-1)

77
Q

What is the function of the acute phase protiens:

granulocyte colony stimulating factor, serum amyloid A, and secreted phospholipase A2?

A

Inflammatory response

78
Q

What is the function of the acute phase proteins:

Finbrinogen, plasminogen, tissue plasminogen factor?

A

Coagulation

79
Q

What acute phase proteins are also able to kill pathogens directly?

A

Compliment proteins

80
Q

What specific interleukin is an important chemoattractant for neutrophils?

A

IL-8

81
Q

What is the function of macrophage inflammatory protein?

A

Chemoattractant for monocytes

82
Q

Which cytokine is the ONLY cytokine of innate immunity to not be produced by macrophages?

A

Interferon gamma

83
Q

Which two cytokines of the innate immune system are anti-inflammatory?

A

Interleukin-10

TGF-beta

84
Q

How does inflammation increase vascular permiability to neutrophils?

A

Endothelial cells start to produce E-Selectin (ES) and P-Selectin (PS)

(Neutrophils have ligands for E-Selectin and P-Selectin on hand at all times)

85
Q

Which cytokine is most important in very early activation of endothelial cells during infection?

A

TNF-alpha

86
Q

What adhesion molecules are found on leukocytes in an unactivated state until they meet chemokines on the endothelial wall?

A

Integrins (such as ICAM-1 and VCAM-1)

87
Q

What four conditions in a phagolysosome make a toxic environment for microbes?

A

Low pH

Presence of ROS (Reactive Oxygen Species)

Presence of NO (Nitric Oxide)

Presence of Lysosomal Proteases

88
Q

Which type of interferons are useful to inhibit viral replication?

A

Type 1 interferons

89
Q

What cell is a major source for Type 1 interferons?

A

Plasmacytoid dendritic cells

90
Q

What three things do Type 1 interferons do to create an antiviral environment?

A

Induces Protein Kinase RNA-activated (PKR) to prevent guanidine diphosphate recycling which prevents viral RNA translation

Activates RNaseL (a latent nuclease) to mediate RNA degradation

Activates NK cells to eliminate infected cells

91
Q

What two signals are required for lymphocyte activation?

A

Recognition of antigen

Costimulators (substances produced during innate immune response)

05. HDM Test 1 (7 decks)

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