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Immunology > DAMPS AND PAMPS > Flashcards

DAMPS AND PAMPS Flashcards

1
Q

What is the dirty little secret from charley Jane way

A

Pathogens associated molecular patterns are recognized by non clonale distribuite receptors found in the host

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2
Q

What is the danger theory by Polly motzinger

A

Immune response are triggered by danger signals released by body owns cells

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3
Q

How does the body recognize danger

A

PAMS pathogen associated molecular patterns that bind to PPR pattern recognition receptors

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4
Q

What are bacteria’s patterns of recognition

A

Liposaccharides
Peptidoglycan
Flagella
Peptides
Unmethylated CpG dna

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5
Q

What are patterns of viruses

A

Double stranded rna
Uncapped rna
Unmethylated DNA

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6
Q

What are pattterns of fungi

A

Beta glucans
Chitin

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7
Q

What are the ppr familys

A
  • toll tile receptors
  • c-lectin
  • nod like receptors
  • rigi like helicases
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8
Q

Which pathways in drosophila confer host defense

A

Toll and Imd

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9
Q

Which pathogens does the toll pathway responds to in drosophila

A

Against fungi and gram positive bacteria

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10
Q

Which protein is essential for the activation of the toll pathway in response to gram positive bacteria in drosophila

A

PGRP-SA

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11
Q

What protein is involved in the activation of the toll pathway in response to fungi

A

Persephone

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12
Q

Which pathway responds to gram negative bacteria in drosophila

A

Imd and the receptor PGRP-LC

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13
Q

What did Bruce Beutler do

A

He identified the gene TLR4 as a candidate gene for resisting to bacterial liposaccharides LPS in mice, TRL4 and LPS they directly interact through hexa-a to lipid A

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14
Q

Where are PRR expressed

A

In innate immune cells

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15
Q

What are the groups of PRR

A
  1. Membrane bound
  2. Cytoplasmatic
  3. Secreted
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16
Q

What re the membrane bound PRR

A

toll like receptors
C-type lectins
Scavenger receptors

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17
Q

What are Cytoplasmatic PRRs

A
  • Nods receptors like nlrps or NALP
  • RNA helicases like RiGI and MAD-5
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18
Q

What are the secreted PRR

A
  • collectins
    Pentraxins
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19
Q

How many toll like receptors do humans have

A

10 functional TLR genes
Mice have 13

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20
Q

TLR 1/2

A

Lipopeptides

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21
Q

TLR 3

A

dsRNA

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22
Q

TLR 4

A

Lps

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23
Q

TLR 5

A

Flagellin

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24
Q

TLR 2+6

A

Lipopeptides

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25
Q

TLR 7

A

Uncapped ssRNA

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26
Q

TLR 8

A

SsRNA

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27
Q

TLR 9

A

CpG DNA

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28
Q

TRL 10

A

Antiinflammatory

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29
Q

TLR 11 only mouse

A

Flagellin

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30
Q

What are DAMPS

A

Endogenous danger molecules

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31
Q

To which TLR does TIRAP becomes an adaptor to between TIR and MyD88

A

TLR 1 , 2 , 4 ,6

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32
Q

Which TLR can recruit MyD88 directly

A

TLR 5, 7, 9 and 11

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33
Q

Which TLR can recruit only Trif

A

TLR 3

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34
Q

Which TLR Recruits TRIF and MyD88

A

TLR 4

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35
Q

which TLR requires the participation of TRAM

A

TLR 4

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36
Q

What happens downstream of those pathways

A

Activation of TF , NFkb and IRF

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37
Q

What genes are induced in the activation of transcription factor during TLR signaling

A

Inflammatory programs, cytokines , chemokines , type one interferons

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38
Q

Who does MyD88 couples to

A

NFkB depended cytokines

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39
Q

What does TRIF couples to

A

Type one interferon

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40
Q

What is IL1

A

Endogenous alarm signal

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41
Q

What proteins are considered IL1

A

IL1 a and IL1 b

42
Q

When are il1 protein produced

A

Inflammatory response

43
Q

Who produces IL1

A

Mainly dendritic cells and macrophages but also many other cells

44
Q

What are the main functions of IL1

A
  • defending against bacterial infections
  • cell migration through upregulation of adhesion molecules
  • bone formation and remodeling
  • fever induction
    -appetite
    -insulin
45
Q

Which pathway does ILR1 SHARES WITH TLR 4

A

Pathway through MyD88 resulting in pro inflammatory cytokines and INFB

46
Q

What Ctype lectin receptor recognize

A

Carbohydrates

47
Q

What does Dectin 1 binds (CLR)

A

Yeast B glucans

48
Q

Where are TLRS AND CLR located

A

Cell surfaces and endosomes

49
Q

Which PRRS protect the cytosol

A

RLRs and NLR

50
Q

What does RIGI like receptor (RLRs) recognize

A

RNA viruses, RIGI and MDA5

51
Q

What does RLR activation leads to

A

Type 1 interferon and inflammatory cytokines response

52
Q

What does RIGI recognized

A

5’ppp short blunt ended dsRNA like in influenza

53
Q

What does MDA5 recognizes

A

Long dsRNA (0.5-7kb) WHITOUT 5’GMP cap

54
Q

What recognized microbial dsDNA

A

cGAS-STING PATHWAY

55
Q

What are the DNA sources of cGAS-STING

A

Microbial DNA
Released mithocondrial dna
Extranuclear chromatin
Cytosolic micronuclei
Aberrant chromosomal DNA

56
Q

What are the downstream pathways of cGAS STING

A

IRF3 ACTIVATION
NFkB and MAPK activation
Authophagy induction
Lysosome mediated cell death and secondary inflammation via NLRP3 inflammsome activation

57
Q

What are the functional consequences of cGAS STING

A

Autoimmune and inflammatory disease
Senescence associated inflammatory response
Tumor associated inflammmation with potential for anti tumor immunogenicity
Increased pathogen clearance

58
Q

What are Nod like receptors

A

Cytoplasmic proteins that regulate inflammatory e\response and cell death pathways
There are more than 20 proteins in t he mammalian genome

59
Q

What do NoD recognize and how do they act

A

They recognize microbial or endogenous danger molecules and they form oligomers that activate inflammatory caspases , they activate important inflammatory cytokines like IL1B and IL18 and NFkB pathways

60
Q

What are the 4 NLR families divided by N terminal domains

A

NLRA
NLRB
NLRC
NLRP

61
Q

What are the subfamilies of NLRs divided to their phylogenetic relationship

A

NOD
NLRP
IPAF

62
Q

What do NOD1 and NOD2 recognize

A

Bacterial peptidoglycans

63
Q

what does NOD1 binds to

A

It binds to me so-diaminopimelic acid (DAP) in gram negative and some gram positive bacteria

64
Q

What does NOD 2 binds to

A

Muramyldipeptide which is the minimal motif found in all gram positive and gram negative bacteria

65
Q

what is NOD 2 important for

A

Production of defensins by Paneth cells

66
Q

What happens with NOD 2 absence in the small intestine

A

Microbial imbalance

67
Q

what happens during Chron disease

A

Rise of Th17 and Th1 inflammatory response

68
Q

Which gene polymorphisms is related to Chrons disease

A

NOD2 DUE TO THE PRODUCTION OF DEFENSINS BY PANETH CELLS

69
Q

What are the main inducers of canonical NFkB pathways

A

1) LPS binding to TLR4 WITH myDD8 and IRAK
2) TNFR1 engages with TNF
3) T cell stimulation in response to antigen presenting cell

70
Q

What are the non canonical NFkB activating pathways

A

Ligands for Bcell activating factor receptor , CD40.

71
Q

What is Sepis

A

The body ‘s extreme response to infection and unlimited PRR stimulation

72
Q

What does SIRS stands for

A

Systematic inflammatory response syndrome

73
Q

What mediates sepis

A

Bacterial products called toxins

74
Q

What defines SIRS systemic inflammatory response symptoms

A

Two or more of the following :
High or low body temperature
Increased hearth beats
Respiratory function of 20 breath per min
Peripheral leukocytes count of 12000 or more mm3

75
Q

Definition of SEPIS

A

Systemic host response to infection with SIRS plus documented infection

76
Q

What’s severe Sepis

A

Sepis plus organ failure end organ dysfunction hypoperfusion

77
Q

What’s a septic shock

A

Sepis with hypotention evidence of inadequate tissue perfusion
The occurrence is 40% of gram negative bacteria and 20% of patients with staphylococcus

78
Q

What are two types of bacterial toxins

A

Exotoxin
Endotoxins

79
Q

What are some characteristics of exotoxins

A
  • secreted proteins
  • plasmid encoded
  • many different ones with diverse mode of action
    -heat sensitive
  • usually no fever
  • effectively neutralized with Ab
80
Q

What are some characteristics of endotoxins

A

LPS in the cell wall
Chromosome encoded
Conserved mode of action
Septic shock
Heat stable
Induce fever
Weak immunogenicity
Gram negative bacteria

81
Q

What’s the sensitivity to LPS in humans

A

50 ug per kg

82
Q

What are the inflammasome

A

Activate oligomeric complexes of NLRPs , it’s an innate response to danger signal
Mainly active in myloid cells
Leads to secretion of IL1B and IL18

83
Q

What are some canonical inflammasonesb

A

NLRP3
NLRP1B
NLRC4
AIM2

84
Q

How does the NLRP3 inflammsoone work

A

nLRP3 activation is critical for oligomerization recruitment and activation of caspases 1 and 11
Which are critical for processing and secreting IL1B and IL18 prior cell death by pyroptosis

85
Q

What are the two steps required for IL1B secretion and pyroptosis

A

1) NFkB activation for transcription and translation
2) inflammsome activation for cleavage of pro IL1B

86
Q

What is gout

A

Is one of the most painful forms of artritis

87
Q

When does Gout occurs

A

When too much uricemie acid is accumulated
Leading to sharp crystal deposits in joints
Kidney stones
1-3% of population

88
Q

How does Punic acid generates

A

By break down of Purines

89
Q

What does uricemie acid crystals (MSU) activate

A

it activates the IL1B pathway through NLRP3 and Caspases 1

90
Q

What inhibits NLRP3 activation

A

Cholchicine used to treat gout

91
Q

What does a mutation in the NLR3 system leads to?

A

Muckle well syndrome (MWS) autoimmune inflammatory disease
Autosomal dominant
As well as gain of function mutations

92
Q

In the MWS patients with a gain of function of NLR3 gene what does occur

A

Spontaneous release of IL1B

93
Q

What is the treatment of MSW

A

IL1B receptor antagonist Anakinra
Rapid decrease of inflammation

94
Q

What is CINCA NOMID

A

CHRONIC INFANTIL NEUROLOGICAL CUTANEOUS AND ARTICULAR SYNDROME

95
Q

What other diseases lead to over activation of NLR3 and IL1B

A

Obesity and diabetes type2

96
Q

What can be done in obese mice with type 2 diabetes to reduce ILB1

A

Caloric restriction which also reduces adipocytes hypertrophy and hyperplasia

97
Q

What is arthereosclerosis

A

Cholesterol storage disease
Lipid deposition and oxidation in artery walls
Important contribution of inflammation and immune cells

98
Q

What else has been identified in arthereosclerosis

A

Elevated CRP C relative proteins plasma levels as an indipendent risk factor for myocardial infarction and stroke

99
Q

What is arthereosclerosis increasingly referred to

A

Chronic inflammatory disease and a causative vicious cycle of arterial lipid deposition and inflammation

100
Q

What are cholesterol crystals inducing

A

IL1B AND IL1A production
(IL1B is dependedt of NLR3 inflammasome complex

101
Q

What reduces arthereosclerosis

A

Anti interlukin 1a/B vaccine in Apo E - deficient mice

102
Q

What is the CANTOS TRIAL

A

Large scale clinical trial to test inflammation hypothesis in humans
Canakinumbam trattena leads to significant changes in end points events

Immunology (11 decks)

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