Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecular & Cellular Immunology > Lecture 4: Innate Sensors > Flashcards

Lecture 4: Innate Sensors Flashcards

1
Q

Why is innate immunity important?

A

Plays crucial role in early recognition of pathogens and triggers proinflammatory response to invading pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does the innate immune system do?

A

Signals to adaptive arms, resolves infection, and promotes angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are examples of sensor cells?

A

Phagocytes and APCs: macrophages, neutrophils, monocytes, dendritic cells, and mast cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are sensor cells and what do they do?

A

Cell types that detect inflammatory mediators through expression of many innate recognition receptors, which remain constant over individuals lifetime

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the result of PAMPs detecting damage via PRRs?

A

Activation, movement, effector function and cytokine production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is phagocytosis?

A

Process of ingestion of a microorganism by a phagocyte via its plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What causes phagocytosis?

A

Occurs after ligation of cell surface receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the 4 steps of phagocytosis?

A

Tasting: receptor mediated binding
Feeling: actin dependent internalisation
Swallowing: phagolysosome degradation
Digesting: antigen processing and presentation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are toll-like receptors?

A

Receptors which are evolutionarily conserved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 3 domains of TLRs?

A
  • N-terminal domain (outside)
  • Middle helix transmembrane domain
  • C-terminal domain (inside)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does dimerisation affect TLRs?

A
  • are monomers or weak dimers during homeostasis
  • activation forms homodimers (TLR4) or heterodimers (TLR1/2)

Dimerisation = stability = signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How many TLRs exist and which ones are species specific?

A

13 types
TLR10: humans, TLR11/12/13: mice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are LRR?

A

Leucine rich repeats found in the TLRs, consisting of 20-25 amino acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the TIR domain and what does it do?

A

Toll-IL-1 receptor, which interacts with signalling molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why do mice have additional TLRs?

A
  • evolutionary adaptation, diverse ecological niches, and specialised immune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where are TIR domains located?

A

Cytosolic side of the plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do TIR domains lead to cell death?

A

TIR domains have weak transient interactions until they self-associate, then create a scaffold that facilitates signal transduction, which leads to immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What pathways is TLR signalling divided into?

A

MyD88-dependent and TRIF-dependent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 4 main TIR-domain containing adaptor proteins?

A

MyD88, TRIF, TIRAP/MAL, and TRAM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the MyD88-dependent pathway?

A

Activates NF-kB and MAPKs for the induction of inflammatory cytokine genes, used by all TLRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the TRIF-dependent pathway?

A

TRIF interrupted to TLR3/4 and promotes an alternative pathway that leads to the activation of IRF3, NK-kB, and MAPKs for induction of type I IFN and inflammatory cytokine genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is NF-kB?

A

Nuclear Factor Kappa B is a protein which controls transcription of DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What does NF-kB do?

A

Is an indictable transcription factor that targets genes involved in inflammation development and progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does NF-kB target inflammation?

A
  • by directly increasing the production of inflammatory cytokines, chemokines and adhesion molecules
  • by regulating the cell proliferation, apoptosis, morphogenesis, and differentiation
25
Q

What does TLR1/2 & TLR2/6 target?

A

Lipoproteins

26
Q

What does TLR1/2 detect?

A

Triacyl lipopeptides

27
Q

What does TLR2/6 detect?

A

Diacyl lipopetides

28
Q

Where are TLR1/2 and 2/6 found?

A

In the cell wall of gram positive bacteria

29
Q

What are alarmins?

A

Endogenous ligands that can be detected by TLR1/2 and TLR2/6, such as heat shock proteins and B-defensin-3

30
Q

How do TLRs 1&2 form a dimer?

A

The convex surface of TLRs 1&2 have binding sites for lipid side chains of triacyl lipopeptides, binding of each TLR indices dimerisation which brings their cytoplasmic TIR domains into close proximity

31
Q

What does TLR3 target?

A

dsRNA in viruses and poly I:C

32
Q

How does homodimerisation activate IRF3?

A

Homidimerisation allows for signalling via TRIF/TRAF3 to activate IRF3

33
Q

How does TLR3 induce gene expression?

A

TLR3 in the endosome binds dsRNA and signals via TRIF to induce IFN gene expression

34
Q

What does TLR4 target?

A

Lipopolysaccharides

35
Q

How does TLR4 use MD-2 accessory protein?

A
  • LPS has multiple fatty acetyl chains linked to a Lucan head = 5 bind to MD-2 pocket, 1 remains free
  • free chain of LPS binds to outer surface of another TLR4 molecule to form dimer
  • dimer is stabilised when another LPS molecule binds to other TLR4
36
Q

How does TLR4 use accessory proteins LBP and CD14?

A
  • LBP binds a monomer of LPS from gram -ve bacteria
  • LBP delivers to soluble/membrane bound CD14 molecule
  • CD14 transfers LPS to the ectodomain of TLR4/MD-2 complex which leads to homodimerisation
  • change in confirmation leads to dimerisation of TIR-domain that provides binding site for MyD88
37
Q

In what 2 ways can TLR4 initiate transcription of proinflammatory cytokines?

A
  • MyD88 activates NF-kB and MAPK signalling, resulting in transcription of proinflammatory cytokines
  • Endocytosis of the LPS.TLR4/MD-2 complex leads to TRIF dependent signalling pathway that mediates induction of IRF3 and IFN-I
38
Q

What does TLR5 target?

A

Flagellin

39
Q

What types of cell is TLR5 expressed in?

A

Monocytes, immature DCs, and epithelial cells

40
Q

How does TLR5 activate IKK complex and NFkB?

A
  • binds flagellin
  • conformational change in TIR allows recruitment of MyD88
  • signals via IRAK, TRAF6, and TAKI
  • leads to activation of IKK complex and NF-kB
41
Q

TLR5 is expressed on basal side of cells - why is this useful?

A

Forms a physical isolation from luminal contents, which helps prevent uncontrolled inflammation by symbiotic microbes

42
Q

What effect does TLR5 activation have?

A
  • Decreases epithelial barrier resistance and reduces expression of tight junction proteins
  • Produces chemokine
  • Attracts immune cells and makes space for the immune cells to access the luminal space
43
Q

What do TLR7 and TLR8 target?

A

GU rich ssRNA

44
Q

What are TLR& and TLR8?

A

Endosomal receptors important for response to viral infection

45
Q

Ho do TLR7 and TLR8 activate cytokine production?

A
  • Signalling is MyD88 dependent, which is mediated by nuclear translocation of AP-1, NF-kB, and IRFs
  • Phosphorylation of IRFs promote induction of IFN-stimulated response elements (ISREs) with expression of type I IFN
  • NF-kB activation results in production of pro-inflammatory cytokines
46
Q

What are IRFs?

A

Interferon regulatory factors

47
Q

What does TLR9 target?

A

Nucleic acid sensors in DNA (unmethylated CpG)

48
Q

What type of ssDNA does TLR9 recognise?

A

Viral and bacterial

49
Q

What does CGAS-STING target?

A

nucleic acid sensors in dsDNA (detects DNA in the cytosol)

50
Q

How does cGAS induce expression of IFNs?

A
  • dsDNA from viruses activates cGAS to produce cGAMP from ATP and GTP
  • cGAMP binds to STING dimer present on the ER membrane and activates its signalling
  • STING activates the kinase TBKI to phosphorylate IRF3
  • IRF3 then enters the nucleus then induces expression of IFN genes
51
Q

What does AIM2 target?

A

Nucleic acid sensors in dsDNA

52
Q

How does AIM2 activation result in pro-ILI or cell death?

A
  • AIM2 inflammasome activates caspase-1
  • Caspase-1 cleaves pro-IL-113 and gasdermins to mediate inflammation and pyroptosis
  • Triggers inflammatory responses through cytokine maturation and pyroptotic cell death
53
Q

What are RIG-I-Like Receptors?

A

Retanoic acid-inducible gene-I lie receptors

54
Q

What are NOD-like receptors?

A

Nucleotide binding oligomerisation domain

55
Q

What are NOD-like receptors?

A

Cytoplasmic innate sensors which initiate NF-kB, and have a CARD domain for Caspase-1 recruitment

56
Q

What do NOD-like receptors target?

A

Cell wall peptidoglycans

57
Q

How do NOD-like receptors initiate NF-kB activation?

A
  • NOD proteins reside in the cytoplasm in inactive form
  • binds to bacterial ligands and induces recruitment of RIP2
  • RIP2 activates TAKI, leading to NF-kB activation
58
Q

How does the NLP inflammasome release inflammatory cytokines?

A
  • potassium efflux induces dissociates of chaperones which keep NLRP3 in inactive form
  • NLRP3 forms oligomers with ASC causing proteolytic cleavage of caspase-I
  • caspase-I releases mature cytokines such as IL-I and IL-18

Molecular & Cellular Immunology (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions