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Immunology > Lec 6: Cellular Innate Responses > Flashcards

Lec 6: Cellular Innate Responses Flashcards

(59 cards)

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1
Q

Is Innate immunity specific?

A

No! it in the host cells first active defense against infection

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2
Q

What PRRs are the innate immune system mediated by

A 
TLRs
RLRs
NLRs
CLRs
ORphan receptors
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3
Q

What transcription factors are activated by the innate immune response

A

IRFs and NFkB

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4
Q

Intrinsic immunity

A

constitutively passive activity, but expression enhanced by innate immune signaling

Produce proteins that negate pathogens and pathogen assembly

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5
Q

Viral restriciton factors produced by the intrinsic immune response

A

Tetherin
APOBEC
TRIM5alpha
many more

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6
Q

PAMPS (examples)

A 
bacterial or viral proteins
bacterial or viral DNA
viral RNA
foreign glycans
toxins
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7
Q

DAMPS (examples)

A

damaged cells

host proteins, and heat shock protiens
host RNA and DNA in the wrong compartment

Purine metabolites (ATP, uric acid) in the extracellular space

hyaluronan fragments

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8
Q

How can PAMPS and DAMPS be hidden

A

PAMPS hidden by glycosylated viruses

DAMPS hidden by apoptotic bodies

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9
Q

TLR signalling

A

cell surface or endosomal location

ligand binding and activation causes TLR homo or hertero dimer formation

ultimately IFN, ISGs and pro-inflammatory genes are induced

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10
Q

PRR recycling

A

initiation of signalling cascades when endocytosed

put back onto cell surface or endosome

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11
Q

What TLR ADAPTOR do bacterial and viral DNA bind to, where is the TLR located

A

MyD88 adaptor protein in the endosome

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12
Q

TLR ligands

A

bind exogenous PAMPS and endogenous DAMPS

key contribution to the pathogenesis of chronic inflammatory disorders

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13
Q

RLR signaling

Location, adaptor protein, oligerimization and what genes are induced

A

cytoplasmic location

Ligand binding and activation induces RLR interaction with adaptor (MAVS/IPS) on mitochondria surface

Signalling requires formation of RLR oligomers

Ultimately IFN, ISGs and pro-inflammatory genes are induced

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14
Q

RLR recognition

A

host RNA has very specific strucutre
=no RNA-DNA duplexes
=multi-structure motifs
=capping ?

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15
Q

RLR recognition

A

host RNA has very specific strucutre
=no RNA-DNA duplexes
=multi-structure motifs
=capping ?

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16
Q

What do RLR receptors recognize

A

helicases so they can unwind DNA/RNA

Helicase and CTD domain bind RNA
5’ PPP RNA
duplex RNA structures such as loops and hairpins

CARD domains
mediate interaction with adaptor protein = MAVS

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17
Q

Host cell vs Viral capping

A

host cell capped with a polyA on 3’ end

single 5’ phosphate capped with capping proeins

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18
Q

RLR ligands

A

unusula RNA structure or modificaiton

discriminate between virla and endogenous RNA based on secondary structure and modificaitons

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19
Q

why do RLRs not bind host mRNA

A

?

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20
Q

Requirements of a vaccine

A

and antigen and an adjevent to activate the immune system

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21
Q

NOD1 and NOD2 sense what

A

bacterial peptidoglycan and adjuvants

NLR receptor

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22
Q

NLRC4 and NAIP5 sense what

A

bacterial flagellin

NLR receptor

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23
Q

NLRP3 senses what

A

vaccine adjuvant = Al(OH)3

NLR receptor

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24
Q

how do NLRs work in synergy with TLRs

Study These Flashcards
A

signal 1 - causes expression of pro-inflammatory gens

25
NLR signaling and inflammasomes, Priming and activation
Priming: NOD1 and NOD2 activate proinflammatory gene transcription (signal 1) Activaiton: NLRP3 (or other) inflammasomes activate caspase 1 which cleaves the pro-form of cytokines IL-1beta and IL-18 into their active forms
26
NLR ligands
Large PRR family with 22 members in humans, even more in mice cytoplasmic sensors or adaptor proteins
27
DNA sensors
dont fit neatly into one group sensors DAI, cGAS and AIM2 detect cytoplasmic DNA PAMP or DAMP derived activators
28
DAI and cGAS activate
IRFs and NFkB signalling (similar to TLR or RIG)
29
AIM2 activates
adaptor protein ASC and drives inflammasome activation | similar to NLR
30
CLR singnalling
receptors bind carbohydrates
31
IL-10
immunosupressive
32
How does the innate immune system react to PRR activaiton NFkB
transcription factor for IFN-responsive genes and pro-inflammatory genes
33
How does the innate immune system react to PRR activaiton IRFs
interferon response factors transcription factor for IFN-responsive gens
34
How does the innate immune system react to PRR activaiton IFNs
interferons (IFNa/IFNb/IFNg) anti-viral cytokines that elicit the activation of hundreds of downstream genes for cellular protection against pathogens
35
How does the innate immune system react to PRR activaiton pro-inflammatory cytokines
promotes an inflammatory response
36
How does the innate immune system react to PRR activaiton ISGs
hundreds of host genes for cellular protection against pathogens includes restriction factors
37
Can you describe first and second wavve interferon signalling
?
38
Interferon
cytokines that initiate antiviral and anti-tumor responses
39
how do inferferons interfere with viral replicaiton in host cells
activate immune cells, up-regulate antigen presentation, initaiate cellular antiviral pathways promote symptoms such as fever and aching muscles during infection
40
Type 1 IFNs
innate: All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α/β receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chainstype I interferons are produced when the body recognizes a virus that has invaded it. They are produced by fibroblasts and monocytes. However, the production of type I IFN-α is inhibited by another cytokine known as Interleukin-10. Once released, type I interferons bind to specific receptors on target cells, which leads to expression of proteins that will prevent the virus from producing and replicating its RNA and DNA IFNb = first wave IFNa = second wave
41
Type 2 IFNs
IFN lambda This is also known as immune interferon and is activated by Interleukin-12. Type II interferons are also released by cytotoxic T cells and type-1 T helper cells. However, they block the proliferation of type-2 T helper cells. The previous results in an inhibition of Th2 immune response and a further induction of Th1 immune response. macrophages and adaptive T cell response
42
Type 3 IFNs
innate: Signal through a receptor complex consisting of IL10R2 (also called CRF2-4) and IFNLR1 (also called CRF2-12). Although discovered more recently than type I and type II IFNs, recent information demonstrates the importance of Type III IFNs in some types of virus or fungal infections IFNg = first wave IL-28 = second wave
43
Can you name an ISG and its function?
?
44
ISGs
genes that are stimulated by transcription factors associated with interferon signaling, such as IRFs and NFkB
45
First wave IFN signalliing is mediated by
PRRs and secretion of cytokines
46
First wave IFN initiates what
anti-viral response within an infected cell inside and infected cell produces IFNs and ISGs
47
Second wave IFN
is a postive amplification loop propagates anti-viral responses throughout the cells of an infected tissue Autocrine or paracrine effects produces more IFNs and ISGs
48
How much IFN is enough
Too much, or not shut off = Death and or tissue damage Too little = pathogen not killed and chronic inflammation
49
Restriction Factors
proteins and enzymes that limit the replication of pathogens in host cells limits pathogen replication are expressed at basal levels and can be induced by IFN signalling cascades -> PRR signaling boosts them Part of a host cell's intrinsic anti-pathogen immunity measures
50
Trex
example of a restriction factor degrades cytoplasmic DNA Humans that have a mutant version of Trex1 mount chronic anti-viral responses, due to presence of ERV DNA = endogenous retrovirues
51
Can you name some vrial restriction factors and their functions?
? see her review article
52
Innate immune system evasion stratagies
degradation of key proteins (viruses can minimize the effectiveness of restriction factors) sequestration of key proteins interrupting protein-protein interactions modulating post-translational modificaitons
53
Tetherin and HIV
teherin is a viral restriction factors that binds to retroviral virions blocks vrius release from the cell surface activates an innate immune response counteracted by HIV
54
HIV protease is a potent inhibitor of innate immune responses
is an apartic protease Introduction of HIV-protease inhibitors has cause a marked decline in HIV-linked OI's HIV-protease also has a direct effect on the RIG-I signalling pathway, (sends it to the lysosome for degrredation)= why redundancy is important!
55
What set of TF drive Type 1 interferon signaling
done by JAK-STAT pathway STAT is a TF maybe it is stat5?
56
Compare and contrast the pathways of: TLRs RLRs NRLs
?
57
Explain how innate immune signalling cascades can work together to boost the innate immune response, give and exammple
(TLR and NRL singlling to drive phase 1) put more doe
58
What mechanisms can pathogens use to evade cellular innate immune responses, give an example
?
59
What are the three key steps for driving the innate immune response?
?

Immunology (23 decks)

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