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Test 1 IBI > B3.004 - Innate Immunity > Flashcards

B3.004 - Innate Immunity Flashcards

1
Q

What is a pathogen

A

a microbe that is causing disease

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2
Q

Necrotic

A

dead cells or tissue from injury or disease

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3
Q

Apoptosis

A

cell death as a normal and controlled part of an organisms growth and development

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4
Q

Cytokines

A

soluble proteins important in cell signaling

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5
Q

Chemokines

A

cytokine that attracts a particular cell into an environment

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6
Q

What is opsonization

A

coating a microbe with molecules that can be recognized by receptors on phagocytes

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7
Q

What is phagocytosis

A

process by which a cell engulfs a solid particle

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8
Q

What is at the initiation of inflammation

A

macrophages, dendritic cells, mast cells secrete cytokines

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9
Q

Viruses induce production of what

A

interferons from from infected cells to inhibit infection of other cells
induce killing by NK cells

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10
Q

What is the cardinal feature of adaptive immunity

A

memory response

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11
Q

What are components of innate immunity

A 
epithelial barriers
dendritic cells
phagocytes
mast cells
NK cells and ILCs
complement
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12
Q

How does adaptive immunity work

A

lymphocytes express receptors on their cell surface that recognize specifiic antigens

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13
Q

What are PAMPs

A

pathogen associated molecular patterns
Shared by microbes of the same type
not on norma host cells
stimulate innate immune response

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14
Q

What are some examples of PAMPs

A

LPS
Peptidoglycans
Terminal mannose residues
Unmethylated CG rich DNA

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15
Q

What are DAMPs

A

Damage associated molecular patterns
Released from damaged or necrotic host cells
present in injury or infection

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16
Q

What are PRRs

A

innate immune receptors that recognize PAMPs and DAMPs

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17
Q

What are TLRs

A

Toll Like Receptors

Specific for microbial components

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18
Q

What do TLRs do

A

activate transcription factors to stimulate expression of genes encoding cytokines, enzymes and other proteins

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19
Q

What is NFkB

A

promotes other items involved in fighting infections

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20
Q

Which TLRs are extracellular

A

1,2,4,6

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21
Q

Which TLRs are intracellular

A

3,7,8,9

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22
Q

What are the steps of TLR signaling

A
  1. TLR engages
  2. Recruits proteins that activate transcription
  3. Increased expression of cytokins, adhesion mols,
  4. Production of type 1 interferon alpha and beta
  5. Generate inflammation
  6. Stimulates adaptive immunity
  7. antiviral activity
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23
Q

What are NLRs

A

NOD like receptors
Family of cytosolic receptors that sense DAMPs and PAMPs in the cytoplasm that contain central NOD and different N terminal domains

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24
Q

NOD 1 and NOD 2 contain

A

N terminal CARD
Bacterial peptidoglycans in the cell wall
Activated NFkB

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25
Q

NLRP3

A

Recognizes microbial products, substances associated with cell damage and endogenous substances in cells in large quntities
Enhances production of IL-1bBeta

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26
Q

What does IL-1bBeta cause

A

inflammation, fever

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27
Q

What are the steps of inflammasome

A
  1. NLRP-3 oligomerizes with inactive form of caspase 1 inlammasome
  2. activation
  3. active caspase 1 cleaves an IL-1beta precursor
  4. activation
  5. IL-1beta generates fever
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28
Q

What can inflammasome dysregulation cause

A

Gout

autoinflammatory syndromes

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29
Q

components of innate immunity

A 
Epithelial varrier
Phagocytes
dendritic cells
mast cells
innate lymphoid cells
NT cells
lymphocytes with limited diversity
complement
plasma proteins
cytokines
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30
Q

what are PMNs

A

polymorphonuclear leukocytes

Neutrophils

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31
Q

what is pus made out of

A

dead phagocytes

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32
Q

what do neutrophils do

A 
First cell to respond to infections
dominant cell of inflammation
phagocytose microbes in the blood and tissue and destroy them
recruited to tissues to remove debris
Live for only a few hours
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33
Q

what are band neutrophils

A

immature neutrophils

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34
Q

What are dendritic cells?

A

Antigen presenting cells that produce cytokines

Bridge innate and adaptive immunity

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35
Q

What are mast cells

A

abundant cytomplasmic vasoactive granules located in the skin and mucosal epithelium

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36
Q

What are mast cells activated by

A

microbial products binding to TLRs

Antibody dependent

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37
Q

What do mast cells synthesize and secrete

A

prostaglandins and ctyokines (TNF)

38
Q

What do NK cells do

A

Identify infected and stressed cells and kill them

CD16/56+

39
Q

What do NK cells secrete

A

IFN gamma to through microphage activation

40
Q

What activates NK cells

A

cytokines from macrophages and dendritic cells

41
Q

What does IL-15

A

development and maturation of NK cells

42
Q

What do IL-12 and type I IFNs do

A

enhance NK cell killing function

43
Q

How do NK cells prevent killing human cells

A

Block signaling by receptor activation specific for self MHC I molecules to protect healthy cells

44
Q

What are ITIMs

A

block NK cell activation, counteracting ITAMs

45
Q

When there is a virus presented to an NK cell what happens

A

NK is activated

ITAMs activated

46
Q

What is ADCC

A

Antibodies recognize viral glycoproteins expressed on the surface of cells infected with enveloped viruses
Therapeutic intervention in treating tumor cells

47
Q

NKT cells and B-1 B cells are what

A

innate lymphocytes

48
Q

What three pathways are in the complement system

A

Alternative, Classical, Lectin

49
Q

What is the Alternative pathway

A

Triggered when activated complement proteins on microbial surfaces are uncontrolled due to lack of regulatory proteins

50
Q

What is the classical pathway

A

Triggered by antibodies bound to microbes/antigens

51
Q

What is the lectin pathway

A

Mannose binding lectin binds to terminal mannose residues on microbial cell surface glycoproteins

52
Q

What do C3a and C5a do

A

they are inflammatory components

53
Q

What does C3b do

A

opsonization and phagocytosis through CR1
Plays a role in complement mediated cytolysis
Stimulates inflammatory reactions

54
Q

What does the MAC do

A

punctures a pore in the microbe to kill it

When C5b combines with C6, C7, C8 and multiple C9

55
Q

As part of the plasma protein innate immunity what are collectins

A

Mannose binding lectins

Surfactant

56
Q

What is MBL

A

recognizes microbial carbohydrates, coating them for phagocytosis
activation of complement by lectin pathway

57
Q

What does surfactant do

A

soap like substance in the lung protective from infectious microbes

58
Q

What is CRP

A

C reactive protein
Binds phosphorylcholine on microbes, opsonizes them for phagocytosis by macrophages
Activates classical complement pathway proteins

59
Q

What are interleukins

A

soluble proteins that cause cell signaling to generate immune and inflammatory reactions - stimulated by infection
Produced by activated and act on leukocytes
Communication between cells

60
Q

What cytokines help in recruitment of neutrophils and monoytes

A

TNF
IL-1
Chemokines

61
Q

What cytokines cause fever by acting on hypothalamus

A

IL-1 predominantly

TNF

62
Q

What cytokine causes an acute phase response protein synthesis from the liver: CRP and fibrinogen

A

IL-6

63
Q

What cytokine causes thrombus formation

A

TNF at high concentration

64
Q

What cytokine causes hypotension

A

TNF at high concentration

65
Q

What cytokines causes septic shock

A

High TNF, IL-12 from dendritic cells and macrophages

66
Q

What are Type 1 Interferons

A

released from DCs, macrophages, fibroblasts

It binds to the virus blocking enzymes necessary for viral replication

67
Q

What do Type 1 Interferons do

A

Inhibit protein syhtnesis
Degrade viral RNA
Inhibit viral gene expression

68
Q

What are the cellular targets and biologic effects of TNF

A 
Endothelial cells - Activation
Neutrophils - activation
Hypothalamus - fever 
Liver - synthesis of acute phase proteins
Muscle/fat - catabolism 
Many cell types - apoptosis
69
Q

What are the principal cellular targets and biological effects of IL-1

A

Endothelial cells - activation (inflammation, coagulation)
Hypothalamus - fever
Liver - sythesis of acute phase proteins
T cells - Th17 differentiation

70
Q

What are the principal targets and biologic effects of chemokines

A

Leukocytes - increased integrin affinity, chemotaxis, activation

71
Q

What is the principal target and biological effect of IL-12

A

NK cells and T cells - IFN gamma production, increased cytotoxic activity
T cells - Th1 differentiation

72
Q

What does IFN gamma do?

A

Activates macrophages

Stimulation of some antibody responses

73
Q

What do Type I IFNs (alpha and beta) do?

A 
All cells - antiviral state, increased class I major histocompatibility complex expression
NK cells - activation
74
Q

What does IL-10 do

A

Macrophages and dendritid cells - inhibition of cytokine and chemokine production, reduced expression of costimulators and class II MHC molecules

75
Q

What does IL-6 do

A

Liver- sythesis of acut phase proteins

B cells - proliferation of antibody producing cells

76
Q

What does IL-15 do

A

NK cells - proliferation

T cells - proliferation

77
Q

What does IL-18 do

A

NK cells and T cells: IFN gamma synthesis

78
Q

What does TGF-beta do

A

inhibits inflammation

T cells - differentiation of Th17, regulatory T cells

79
Q

Which disease has defective production of reactive oxygen intermediates by phagocytes

A

Chronic granulomatous disease

80
Q

What is the mechanism of defect of chronic granulomatous disease

A

mutations in genes encoding components of the phagocyte oxidase enzyme, most often cytochorme b558

81
Q

What disease has absent or deficient expression of Beta 2 integrins causing defective leukocyte adhesion dependent function

A

Leukocyte adhesion deficiency - 1

82
Q

What is the mechanism of defect of Leukocyte adhesion deficiency - 1

A

Mutations in gene encoding the beta chain CD28 of beta 2 integrins

83
Q

What disease has absent or deficient expression of leukocyte ligands for endothelial E and P selectins, causing failure of leukocyte migration into tissues

A

Leukocyte adhesion deficiency -2

84
Q

What is the mechanism of defect of leukocyte adhesion deficiency -2

A

mutations in gene encoding a protein required for synthesis of sialyl-Lewis X component of E and P selectin ligands

85
Q

What disease has a defect in complement cascade activation

A

Complement C3 deficiency

86
Q

What disease has deficient activation of classical pathway of complement leading to failure to clear immune complexes and development of lupus like disease

A

Complement C2, C4 deficency

87
Q

What disease has a defective lysosomal function in neutrophils, macrophages, dendritic cells, and effective granule function in natural killer cells

A

Chediak higashi syndrome

88
Q

What mechanism of defect is there for Chediak Higash syndrome

A

Mutation in a gene encoding a lysosomal trafficking regulatory protein

89
Q

What disease has a defective antiviral immunity in the CNS

A

HSV-1 encephalitis

90
Q

What mutation can lead to worse outcomes for HSV-1 like encephalitis

A

Mutations in TLR3 gene

91
Q

What disease has defective innate immune responses to pyogenic bacteria

A

recurrent pyogenic bacterial infections

92
Q

What doe PRRs do

A

recognize nucleic acids but they are located in cellular components where healthy cells are not accessible

Test 1 IBI (8 decks)

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