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
2
Q
What is the danger theory by Polly motzinger
A
Immune response are triggered by danger signals released by body owns cells
3
Q
How does the body recognize danger
A
PAMS pathogen associated molecular patterns that bind to PPR pattern recognition receptors
4
Q
What are bacteria’s patterns of recognition
A
Liposaccharides
Peptidoglycan
Flagella
Peptides
Unmethylated CpG dna
5
Q
What are patterns of viruses
A
Double stranded rna
Uncapped rna
Unmethylated DNA
6
Q
What are pattterns of fungi
A
Beta glucans
Chitin
7
Q
What are the ppr familys
A
- toll tile receptors
- c-lectin
- nod like receptors
- rigi like helicases
8
Q
Which pathways in drosophila confer host defense
A
Toll and Imd
9
Q
Which pathogens does the toll pathway responds to in drosophila
A
Against fungi and gram positive bacteria
10
Q
Which protein is essential for the activation of the toll pathway in response to gram positive bacteria in drosophila
A
PGRP-SA
11
Q
What protein is involved in the activation of the toll pathway in response to fungi
A
Persephone
12
Q
Which pathway responds to gram negative bacteria in drosophila
A
Imd and the receptor PGRP-LC
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
14
Q
Where are PRR expressed
A
In innate immune cells
15
Q
What are the groups of PRR
A
- Membrane bound
- Cytoplasmatic
- Secreted
16
Q
What re the membrane bound PRR
A
toll like receptors
C-type lectins
Scavenger receptors
17
Q
What are Cytoplasmatic PRRs
A
- Nods receptors like nlrps or NALP
- RNA helicases like RiGI and MAD-5
18
Q
What are the secreted PRR
A
- collectins
Pentraxins
19
Q
How many toll like receptors do humans have
A
10 functional TLR genes
Mice have 13
20
Q
TLR 1/2
A
Lipopeptides
21
Q
TLR 3
A
dsRNA
22
Q
TLR 4
A
Lps
23
Q
TLR 5
A
Flagellin
24
Q
TLR 2+6
A
Lipopeptides
25
TLR 7
Uncapped ssRNA
26
TLR 8
SsRNA
27
TLR 9
CpG DNA
28
TRL 10
Antiinflammatory
29
TLR 11 only mouse
Flagellin
30
What are DAMPS
Endogenous danger molecules
31
To which TLR does TIRAP becomes an adaptor to between TIR and MyD88
TLR 1 , 2 , 4 ,6
32
Which TLR can recruit MyD88 directly
TLR 5, 7, 9 and 11
33
Which TLR can recruit only Trif
TLR 3
34
Which TLR Recruits TRIF and MyD88
TLR 4
35
which TLR requires the participation of TRAM
TLR 4
36
What happens downstream of those pathways
Activation of TF , NFkb and IRF
37
What genes are induced in the activation of transcription factor during TLR signaling
Inflammatory programs, cytokines , chemokines , type one interferons
38
Who does MyD88 couples to
NFkB depended cytokines
39
What does TRIF couples to
Type one interferon
40
What is IL1
Endogenous alarm signal
41
What proteins are considered IL1
IL1 a and IL1 b
42
When are il1 protein produced
Inflammatory response
43
Who produces IL1
Mainly dendritic cells and macrophages but also many other cells
44
What are the main functions of IL1
- defending against bacterial infections
- cell migration through upregulation of adhesion molecules
- bone formation and remodeling
- fever induction
-appetite
-insulin
45
Which pathway does ILR1 SHARES WITH TLR 4
Pathway through MyD88 resulting in pro inflammatory cytokines and INFB
46
What Ctype lectin receptor recognize
Carbohydrates
47
What does Dectin 1 binds (CLR)
Yeast B glucans
48
Where are TLRS AND CLR located
Cell surfaces and endosomes
49
Which PRRS protect the cytosol
RLRs and NLR
50
What does RIGI like receptor (RLRs) recognize
RNA viruses, RIGI and MDA5
51
What does RLR activation leads to
Type 1 interferon and inflammatory cytokines response
52
What does RIGI recognized
5’ppp short blunt ended dsRNA like in influenza
53
What does MDA5 recognizes
Long dsRNA (0.5-7kb) WHITOUT 5’GMP cap
54
What recognized microbial dsDNA
cGAS-STING PATHWAY
55
What are the DNA sources of cGAS-STING
Microbial DNA
Released mithocondrial dna
Extranuclear chromatin
Cytosolic micronuclei
Aberrant chromosomal DNA
56
What are the downstream pathways of cGAS STING
IRF3 ACTIVATION
NFkB and MAPK activation
Authophagy induction
Lysosome mediated cell death and secondary inflammation via NLRP3 inflammsome activation
57
What are the functional consequences of cGAS STING
Autoimmune and inflammatory disease
Senescence associated inflammatory response
Tumor associated inflammmation with potential for anti tumor immunogenicity
Increased pathogen clearance
58
What are Nod like receptors
Cytoplasmic proteins that regulate inflammatory e\response and cell death pathways
There are more than 20 proteins in t he mammalian genome
59
What do NoD recognize and how do they act
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
What are the 4 NLR families divided by N terminal domains
NLRA
NLRB
NLRC
NLRP
61
What are the subfamilies of NLRs divided to their phylogenetic relationship
NOD
NLRP
IPAF
62
What do NOD1 and NOD2 recognize
Bacterial peptidoglycans
63
what does NOD1 binds to
It binds to me so-diaminopimelic acid (DAP) in gram negative and some gram positive bacteria
64
What does NOD 2 binds to
Muramyldipeptide which is the minimal motif found in all gram positive and gram negative bacteria
65
what is NOD 2 important for
Production of defensins by Paneth cells
66
What happens with NOD 2 absence in the small intestine
Microbial imbalance
67
what happens during Chron disease
Rise of Th17 and Th1 inflammatory response
68
Which gene polymorphisms is related to Chrons disease
NOD2 DUE TO THE PRODUCTION OF DEFENSINS BY PANETH CELLS
69
What are the main inducers of canonical NFkB pathways
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
What are the non canonical NFkB activating pathways
Ligands for Bcell activating factor receptor , CD40.
71
What is Sepis
The body ‘s extreme response to infection and unlimited PRR stimulation
72
What does SIRS stands for
Systematic inflammatory response syndrome
73
What mediates sepis
Bacterial products called toxins
74
What defines SIRS systemic inflammatory response symptoms
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
Definition of SEPIS
Systemic host response to infection with SIRS plus documented infection
76
What’s severe Sepis
Sepis plus organ failure end organ dysfunction hypoperfusion
77
What’s a septic shock
Sepis with hypotention evidence of inadequate tissue perfusion
The occurrence is 40% of gram negative bacteria and 20% of patients with staphylococcus
78
What are two types of bacterial toxins
Exotoxin
Endotoxins
79
What are some characteristics of exotoxins
- secreted proteins
- plasmid encoded
- many different ones with diverse mode of action
-heat sensitive
- usually no fever
- effectively neutralized with Ab
80
What are some characteristics of endotoxins
LPS in the cell wall
Chromosome encoded
Conserved mode of action
Septic shock
Heat stable
Induce fever
Weak immunogenicity
Gram negative bacteria
81
What’s the sensitivity to LPS in humans
50 ug per kg
82
What are the inflammasome
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
What are some canonical inflammasonesb
NLRP3
NLRP1B
NLRC4
AIM2
84
How does the NLRP3 inflammsoone work
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
What are the two steps required for IL1B secretion and pyroptosis
1) NFkB activation for transcription and translation
2) inflammsome activation for cleavage of pro IL1B
86
What is gout
Is one of the most painful forms of artritis
87
When does Gout occurs
When too much uricemie acid is accumulated
Leading to sharp crystal deposits in joints
Kidney stones
1-3% of population
88
How does Punic acid generates
By break down of Purines
89
What does uricemie acid crystals (MSU) activate
it activates the IL1B pathway through NLRP3 and Caspases 1
90
What inhibits NLRP3 activation
Cholchicine used to treat gout
91
What does a mutation in the NLR3 system leads to?
Muckle well syndrome (MWS) autoimmune inflammatory disease
Autosomal dominant
As well as gain of function mutations
92
In the MWS patients with a gain of function of NLR3 gene what does occur
Spontaneous release of IL1B
93
What is the treatment of MSW
IL1B receptor antagonist Anakinra
Rapid decrease of inflammation
94
What is CINCA NOMID
CHRONIC INFANTIL NEUROLOGICAL CUTANEOUS AND ARTICULAR SYNDROME
95
What other diseases lead to over activation of NLR3 and IL1B
Obesity and diabetes type2
96
What can be done in obese mice with type 2 diabetes to reduce ILB1
Caloric restriction which also reduces adipocytes hypertrophy and hyperplasia
97
What is arthereosclerosis
Cholesterol storage disease
Lipid deposition and oxidation in artery walls
Important contribution of inflammation and immune cells
98
What else has been identified in arthereosclerosis
Elevated CRP C relative proteins plasma levels as an indipendent risk factor for myocardial infarction and stroke
99
What is arthereosclerosis increasingly referred to
Chronic inflammatory disease and a causative vicious cycle of arterial lipid deposition and inflammation
100
What are cholesterol crystals inducing
IL1B AND IL1A production
(IL1B is dependedt of NLR3 inflammasome complex
101
What reduces arthereosclerosis
Anti interlukin 1a/B vaccine in Apo E - deficient mice
102
What is the CANTOS TRIAL
Large scale clinical trial to test inflammation hypothesis in humans
Canakinumbam trattena leads to significant changes in end points events
