Chapter 4 Flashcards

1
Q

What is the major signal transduction pathway that TLR engage to activate cells?

A

NF-kB

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2
Q

Receptors of innate immune system are encoded by () genes whereas receptors of adaptive immunity are generated by () genes.

A

Germline gene

Somatic gene

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3
Q

Name the structures recognised by innate immune system.

1) molecules produced by microbial pathogens
2) endogenous molecules produced by damaged cells

A

1) PAMP (pathogen-associated molecular patterns)

2) DAMP (damage-associated molecular patterns)

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4
Q

List the entities under PAMP & DAMP.

A

PAMP (nucleic acids, proteins, cell wall lipids, carbohydrates)

DAMP (stress-induced proteins, crystals, proteolytically cleaved ECM, mitochondria, nuclear proteins)

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5
Q

List the entities under cell-associated & soluble pattern recognition receptors.

A

Cell-associated PRP

  • membrane (TLR, CLR, scavenger receptors, N-Formyl met-leu-phe receptors)
  • cytosolic (NLR, RLR, CDS)

Soluble PRP
- pentraxins, collectins, ficolins, complement

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6
Q

What is the signalling structure for TLR?

This structure is also found in () & ().

A

Toll/IL-1 receptor (TIR) domain in cytoplasmic tails

*TIR is also found in IL-1 & IL-8.

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7
Q

TLR also recognises endogenous molecules whose expression or location indicate cell damage. What are these molecules?

A

HSP (heat shock proteins)

HMGB1 (for transcription & DNA repair)

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8
Q

() & () bind to lipid A of LPS, forming a complex that interacts with TLR4 & initiates signalling.

A

MD2 (myeloid differentiation protein 2)

CD14 (for efficient LPS-induced signalling)

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9
Q

Which protein in ER is required for endosomal localisation & proper function of TLR3, 7, 8 & 9?
Genetic deficiency of this protein leads to susceptibility of which infection?

A

UNC-93B

Herpes simplex encephalitis

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10
Q

All TLRs signal through MyD88 except ().

The above TLR signals through ().

A

TLR3

TRIF

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11
Q

Which TLR signals through MyD88 & TRIF?

A

TLR4

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12
Q

These TLR are most highly expressed in plasmacytoid DC, signal through MyD88-dependent, TRIF-independent pathway that activates NF-kB & IRF.

A

Endosomal TLR7 & TLR8

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13
Q

Name 3 major transcription factors activated by TLR.

A

Nuclear factor kB (NF-kB)
Activation protein (AP-1)
Interferon response factor (IRF3 & IRF7)

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14
Q

Name the surface TLR(s) that recognise

1) bacterial polypeptide
2) bacterial peptidoglycan
3) lipopolysaccharide
4) bacterial flagellin

A

1) TLR1:TLR2 & TLR2:TLR6
2) TLR2
3) TLR4
4) TLR5

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15
Q

Name the endosomal TLR(s) that recognise

1) dsRNA
2) ssRNA
3) CpG DNA

A

1) TLR3
2) TLR7 & TLR8
3) TLR9

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16
Q

Name 4 cytosolic receptors for PAMP & DAMP.

A

NOD-like receptors (NLR)
Cytosolic DNA sensors (CDS) & STING pathway
RIG-like receptors (RLR)
Inflammasomes

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17
Q

Name 3 NLR subfamilies & their respective effector domain that serve innate immunity.

A

NLRB uses BIR
NLRC uses CARD (NOD1 & NOD2)
NLRP uses Pyrin

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18
Q

Defect in Pyrin domain of NLRP causes which disease?

And what’s the gene involved?

A

Familial Mediterranean fever in MEFV gene mutation

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19
Q

NOD2 is produced by () which recognises () to stimulate expression of (). Gain-of-function mutation of NOD2 causes increased NOD signalling & NF-kB activation leading to ().

A

Paneth cells
MDP (muramyl dipeptide)
Defensins
Blau syndrome

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20
Q

NOD1 recognises () derived mainly from gram-negative bacterial peptidoglycan.

A

DAP (diaminopimelic acid)

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21
Q

Function of NLRB.

A

Detect flagellin to control Legionella pneumophila infection.

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22
Q

Function of NLRP.

A

Caspase 1 activation

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23
Q

CDS detects () in cytosol & induces () pathway which is ()-induced activation of () responses.

A

microbial dsDNA
STING (stimulator of IFN genes)
dsDNA
Type 1 IFN

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24
Q

Name 2 CDS that work through STING independent pathway.

A

RNA polymerase 3 activates RIG-1 pathway.

AIM2 forms inflammasome, generates IL-1b.

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25
Q

() is the cytosolic sensor of viral RNA (dsRNA & RNA-DNA) that respond by inducing production of antiviral type 1 interferons.

A

RIG-like receptors (RLR)

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26
Q

Give 2 examples of RLR.

A

RIG-1 (retinoid-inducible gene 1)

MDA5 (melanoma differentiation-associated gene 5)

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27
Q

RLR are recruited to outer mitochondrial membranes by () which activates (), () & () to induce type 1 interferon production.

A

MAVS (mitochondrial antiviral-signalling) protein

IRF3, IRF7 & NF-kB

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28
Q

Functions of inflammasomes.

A

To generate active form of IL-1b & IL-18 (caspase-1)

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29
Q

Inflammasome activation causes () characterised by apoptosis of macrophage & DC but not neutrophils & others.

A

Pyroptosis

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30
Q

() recognise microbial surface carbohydrates to facilitate microbe phagocytosis & chemokine secretion.

A

C-type lectin receptors

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31
Q

Name the C-type lectin receptor involved in

1) phagocytosis
2) antifungal immunity
3) Th17 differentiation
4) mycobacterium immunity
5) hepatitis C virus & HIV-1 infection

A

1) mannose receptors, langerin
2) mannose receptors, Dectin-1, Dectin-2 & Mincle
3) Dectin-1 & Dectin-2
4) Dectin-2 & Mincle
5) DC-Sign

32
Q

Scavenger receptors mediate uptake of () into cells via expression of () & () on macrophage.

A

Oxidised lipoproteins

SR-A & CD36

33
Q

() expressed in leukocytes, recognises bacterial peptides containing N-formylmethionyl residues & stimulates directed cell movement.

A

Formyl-peptide receptor 1 (FPR1)

34
Q

() is mainly produced by () in small bowel to limit the amount of luminal microbes in which they kill microbes by disrupting function of microbial membranes.

A

alpha-defensins (crypticidin)

Paneth cell

35
Q

() produced by neutrophils & mucosal epithelium protect against infections by direct toxicity & leukocyte activation.

A

Cathelicidin

36
Q

C-terminal fragment of cathelicidin named () can bind & neutralise LPS that is recognised by TLR4.

A

LL-37

37
Q

() is the major source of antiviral cytokines type 1 IFN due to abundant expression of ().

A
Plasmacytoid DC
endosomal TLR (3, 7, 8, 9)
38
Q

Name the cytokines responsible for

1) defense against viruses
2) defense against helminths & allergic inflammation
3) intestinal barrier function & lymphoid organogenesis

A

1) IFN-gamma
2) IL-5 & IL-13
3) IL-17 & IL-22

39
Q

Which cytokines are responsible for innate lymphoid cells (ILC) development?

A

IL-7 (for ILC1, ILC2 & ILC3)

IL-15 (for ILC1)

40
Q

NK cells are identified by expression of () and () & absence of ().

A

CD56 & CD16

CD3

41
Q

Name 2 NK cells granules.

Name cytokines responsible for NK cell expansion & activation.

A

Perforin & granzyme

IL-12, IL-15, IL-18 & type 1 IFN

42
Q

Activating receptors of NK cells transmit signals via ().

Entities include…

A

ITAM (immunoreceptor tyrosine-based activation motifs)

KIR, NKG2D & CD16

43
Q

Inhibitory receptors of NK cells recognise () & transmit signals via (). Entities include…

A

Class 1 MHC
ITIM (immunoreceptor tyrosine-based inhibition motif)
KIR & lectins

44
Q

Name 4 entities of soluble effector molecules of innate immunity.

A

Complement system
Pentraxins
Collectins
Ficolins

45
Q

() activate complement by binding C1q & initiating classical pathway.

A

Pentraxins

46
Q

Name 4 entities of pentraxins.

A

Short pentraxins
C-reactive proteins (CRP)
Serum amyloid P (SAP)
Long pentraxins PTX3

47
Q

CRP synthesis in liver is induced by () & ().

A

IL-1 & IL-6

48
Q

() provides protection against microbes including Aspergillus fumigatus & influenza virus.

A

Long pentraxin PTX3

49
Q

Name 2 members of collectin.

A

Mannose-binding lectin (MBL)

Pulmonary surfactant proteins SP-A & SP-D

50
Q

() has fibrinogen-type carbohydrate recognition domain which functions to opsonise bacteria & activate complement like MBL.

A

Ficolins

51
Q

Name the 2 molecular ligands of ficolins.

A

N-acetylglucosamine

Lipoteichoic acid

52
Q

2 cytokines that induce Th17 differentiation.

A

IL-1 & IL-6

53
Q

Which cytokine induces Th1 differentiation.

A

IL-12

IL-27

54
Q

Name the type 1 interferons that is produced by

1) macrophage & plasmacytoid DC
2) fibroblast

A

1) IFN-alpha

2) IFN-beta

55
Q

This cytokine inhibits expression of IL-12.

A

IL-10

56
Q

This cytokine induces proliferation of memory CD8+ T cells.

A

IL-15

57
Q

This cytokine maintains IL-17-producing T cells.

A

IL-23

58
Q

This cytokine induces Th1 differentiation & Th17 inhibition.

A

IL-27

59
Q

Which TNF receptor activates caspase & apoptosis?

A

Type 1 TNF receptor (TNF-RI)

60
Q

Septic shock is largely mediated by which cytokine?

A

TNF

61
Q

Name 1 mediator of acute inflammatory response with many similar actions with TNF & its entities.

A

IL-1 (IL-1a & IL-1b)

62
Q

() cleaves gasdermin D for non-canonical inflammasome signalling in pyroptosis.

A

Caspase-11

63
Q

() cleaves pro-IL-1b to IL-1b.

A

Caspase-1

64
Q

() which contains gp130 that activates STAT3, is a major contributor to rheumatoid arthritis.

A

IL-6

65
Q

() is caused by HHV-8 that encodes IL-6 homolog.

A

Castleman’s disease

66
Q

TNF & IL-1 induce postcapillary venule endothelial cell to express () & stimulate () and () secretion which bind to receptors of neutrophils & monocytes respectively.

A

E-selectin

CXCL8 & CCL2

67
Q

() is produced by phagocyte oxidase in respiratory burst in which its deficiency leads to ().

A

Reactive oxygen species (ROS)

Chronic granulomatous disease

68
Q

Intracellular destruction of microbes in phagolysosome involves () & ().

A

ROS & NO

69
Q

Nitric oxide is produced by () in macrophage.

A

Inducible nitric oxide synthase (iNOS)

70
Q

Name 2 enzymes of neutrophils & their respective functions.

A
Elastase (broad-spectrum serine protease to kill bacteria)
Cathepsin G (phagocytosis)
71
Q

Neutrophil extracellular traps (NETs) formation in NETosis requires histone citrullination by 4 enzymes.

A

Peptidylarginine deiminase (PAD4)
Elastase
Myeloperoxidase (MPO)
Phagocyte oxidase

72
Q

This cytokine is responsible for intravascular thrombosis & cachexia.

A

TNF

73
Q

Cytokine for septic shock outcome prediction.

A

TNF

74
Q

Cytokines in autoimmune diseases.

A

TNF
IL-1
IL-6
IL-12

75
Q

Name 4 mechanisms in limiting innate immune response.

A

IL-10
IL-1RA
Autophagy genes
Negative regulatory signalling pathway

76
Q

() are inhibitors of JAK-STAT signalling pathways linked to cytokine receptors.

A

Suppressors of cytokine signalling (SOCS) proteins

77
Q

List the inducer cytokines & T cells responsible for the following situations.

1) defense against intracellular pathogens
2) defense in allergy & asthma
3) anti-tumour & prevent autoimmunity
4) immune regulation
5) defense against extracellular bacteria
6) defense against autoimmunity
7) defense against viral infection

A

1) IL-12 & Th1
2) IL-4 & Th2
3) IL-4/TGF-b & Th9
4) IL-2/TGF-b & Treg
5) IL-6/TGF-b & Th17
6) IL-6/IL-21 & Tfh
7) IL-15 & NKT cell