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Basic Immunology- Module 1 > Chapter 3 > Flashcards

Chapter 3 Flashcards

1
Q

Where do macrophages derive from?

A

progenitor cells that enter tissues during emrbyonic development and self-renew or from circulating monocytes

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2
Q

Where do the embyronic progenitors of macrophages derive from?

A

fetal liver; yolk sac or the aorta-gonad-mesonephros

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3
Q

What cytokine does self-renewal of microglial cells and Kupffer cells rely on?

A

IL-34

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4
Q

What receptor do classical monocytes express?

A

CD14

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5
Q

What receptors do patrolling monocytes express?

A

CD14 and CD16

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6
Q

What are the 3 methods by which pathogens can be taken into the cell?

A

phagocytosis; receptor-mediated endocytosis and macropinocytosis

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7
Q

What are the phagocytic receptors present on macrophages and neutrophils?

A

C-type lectin family; scavenger receptors; complement receptors; Fc receptors

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8
Q

what is the function of dectin-1?

A

recognises b-1,3-linked glucans

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9
Q

What cells are b-1,3-linked glucans found on?

A

fungi

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10
Q

Which cells express mannose receptor?

A

macrophages and denritic cells

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11
Q

What does the mannose receptor recognise?

A

mannosylated ligands

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12
Q

What is thought to be the function of mannose receptors?

A

mainly as a clearance recpetor for host glycoproteins which have mannose containing side chains and whose extra-cellular concentrations are raised during inflammation

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13
Q

What do scavenger receptors recognise?

A

anionic polymers and acetylated low-density lipoproteins

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14
Q

Give an emaple of a GPCR involved in pathogen recognition and killing?

A

fMet-Leu-Phe receptor ; Chemokine receptors

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15
Q

What amino acid usually initiates protein synthesis in bacteria?

A

fMet residue

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16
Q

What happens when fMLF binds its ligand?

A

activates intracellular signalling that direct the cell to move toward th e most concentrated source of hte ligand; induces production of ROS in the phagolysosome

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17
Q

What proteins are activated in response to f-Met-Leu-Phe activation?

A

Rho family of small GTAse proteins: Rac and Rho

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18
Q

What is the function of Rac in the assembly of NADPH oxidase?

A

promotes the movement of cytosolic compoenets of the enzyme to the phagolysosomal membrane and assmble the full enzyme

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19
Q

what is the function of NADPH oxidase?

A

generates superoxide- a reactive oxygen species (NAPH—NAP+ and H+)

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20
Q

What does the NADPH oxidase reaction cause?

A

a transient increase in oxygen consumption by the cell:respiratory burst- as the electron from NADPH oxidase reaction is transferred to oxygen

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21
Q

What does the respiratory burst cause?

A

generates superoxide anion within the lumen of hte phagolysosome

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22
Q

What enzyme converts the superoxide anion into hydrogen peroxide?

A

superoxide dismutase

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23
Q

What disease results from a genetic deficiency of NADPH oxidase?

A

chronic granulomatous disease

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24
Q

What type of infection are patients with CGD particularly susceptible to?

A

bacterial and fungal infections

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25
Q

What receptors synergise to activate Rac?

A

phagocytic recpetors and fMLF or C5a

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26
Q

How is the pH decreased in the phagolysosome?

A

potasssium and hydrogen ions are drawn into the phagolysosome to neutralise the charged superoxide ion

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27
Q

What does NET formation rely upon?

A

generation of ROS

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28
Q

What are monocytes attracted to a site of inflammation and activated called?

A

inflammatory monocytes

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29
Q

How are monocytes distinguished from macrophages?

A

monocytes lack of expression of the adhesion GPCR E1- F4/80

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30
Q

What 2 systems are activated by actiavted endothelial cells in resposne to infection/injury?

A

kinin system and coagulation system

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31
Q

What is the function of the coagulation system in infection?

A

clot physically stops the spread of infection through the blood

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32
Q

What is the function of bradykinin in infection?

A

increases permeability of the endothelial cells and causes pain

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33
Q

What is the function of TLRs in the endosomal spaces?

A

recognise pathogens taken up by phagocytosis (phagosome-type of endosome); receptor-mediated endocysosis and macropinocytosis

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34
Q

What cytokine receptor has a TIR domain?

A

IL-1b

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35
Q

What is the difference between Tol receptors in drosdophila and in mammals?

A

Tol receptors do not receognise microbial products directly but respond to a self protein Spatzle which is created in response to activation of direct pathogen-recognition molecules

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36
Q

What is found in the extracellular region of TLRs?

A

28-25 copies of LRRs

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37
Q

What cells are TLR-1, TLR-2 and TLR-6 found on?

A

macrophages; mast cells; eosinohpils; dendritic cells and basophils

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38
Q

What other receptors apart from TLRs cooperate with TLR-2 in ligand recognition?

A

scavenger receptor CD36 which binds long-chain fatty chains; dectin-1- beta-glucans

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39
Q

What cells is TLR-5 expressed on?

A

macrophages, dendritic cells and intestinal epithelial cells

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40
Q

How many TLRs do mice express?

A

12

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41
Q

How many TLRs do humans express?

A

10

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42
Q

What do TLR11 and TLR12 share with TLR5?

A

recognise an intact protein

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43
Q

What cells express TLR-3?

A

macrophages, conventiional dendritic cells and intestinal epithelial cells

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44
Q

What pathogens is double-stranded RNA found in?

A

viruses- those with RNA genomes and also produced as a replicative intermediate of many types of virus

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45
Q

What do mutations in the ectodomain of TLR-3 cause?

A

mutatnt recpetor which results in susceptibility ot herpes-simplex encephalitis

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46
Q

What cells express TLR-7 and TLR-9?

A

plasmacytoid dendritic cells, B cells and eosinophils

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47
Q

what cells express TLR-8?

A

monocytes and macrophages

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48
Q

Why odo TLR7 and TLR8 not respond to single stranded RNA that is produced in healthy mammalian cells?

A

present in the nucleus and cytoplasm not in endosomes

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49
Q

give examples of viruses which consist of ssRNA?

A

influenza and flaviviruses

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50
Q

What is the difference between CpG dinucleotides in humans and in pathogens?

A

methylation

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51
Q

What does delivery of TLR3, TLR-7 and TLR-9 rely on?

A

interaction with UNC93B1

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52
Q

What does deficiency of UNC93B1?

A

susceptibility to herpes simplex encephalities similar to deficiency of TLR3

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53
Q

What is the function of MD2?

A

correct trafficking of TLR4 and recognition of LPS

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54
Q

How does MD2 help in the recognition of LPS?

A

binds 5 lipid chains of LPS leaving one exposed which binds to nother TLR4 ectodomain causing TLR dimerization

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55
Q

What is free LPS bound to LPS-binding protein transferred to?

A

CD14 (which can act as a phagocytic receptor on its own)

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56
Q

Which cells is CD14 present on?

A

macrophages; neutrophils and dendritic cells

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57
Q

What does CD14 act as in addition to being a phagocytic receptor on macrophages and dendritic cells?

A

an accessory protein for TLR-4

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58
Q

Which adaptor proteins do TLR-2 heterodimers use?

A

MyD88/MAL

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59
Q

Which adaptor proteins does TLR-4 use?

A

both MyD88/MAL and TRIF/TRAM

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60
Q

Which adaptor protein does TLR-3 use?

A

only TRIF

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61
Q

What is the function of the choice of adaptor by TLRs?

A

influences which of the several downstream signals will be activated by the TLR

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62
Q

What does the signalling pathway for AP-1 invovle?

A

mitogen-activated protein kinases

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63
Q

What is the primary function of NFkB and AP-1 activation?

A

expression of pro-inflammatory cytokine and chemotactic factors

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64
Q

Which IRF factors induce antiviral type 1 interferons?

A

IRF3 and IRF7

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65
Q

Which IRF factors produce pro-inflammatory cytokines?

A

IRF5

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66
Q

What is found at the carboxy-terminus of MyD88?

A

TIR domain

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67
Q

What is found at the N-terminal of My-D88?

A

death domain

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68
Q

What happens if there is a mutation in either domain of MyD88?

A

immunodeficiency with recurrent bacterial infections

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69
Q

What does the MyD88 death domain recruit?

A

IRAK1 and IRAK4 via their death domains

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70
Q

What are IRAK1 and IRAK4?

A

serine-threonine protein kinases

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71
Q

What is the function of the IRAK complex/

A

recruits enzymes that produce a signalling scaffold and uses this scaffold to recruit other molecules which are phosphorylated by IRAK

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72
Q

What enzyme does the IRAK complex recruit to form a signalling scaffold?

A

TRAF6

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73
Q

What type of enzyme is TRAF6?

A

E3 ubiquitin ligase

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74
Q

What does TRAF6 work in combination with?

A

UBC13

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75
Q

What does the TRAF6 and UBC13 and its cofactor cause?

A

the production of a polyubiquitin chain which acts as a scaffold

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76
Q

What does the polyubiquitin chain recruit?

A

TAB1/2 and TAK1

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77
Q

What is the function of activated TAK1?

A

can activate MAPKs to activate AP-1 as well as IKK

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78
Q

What is the IkB kinase complex composed of?

A

IKKa; IKKb and IKKy

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79
Q

What does activated IKKb do?

A

phosphorylates IkB

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80
Q

What is IkB?

A

a cytoplasmic protein which binds to NFkB composed of p50 and p65

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81
Q

What cytokines does NFkB induce production of?

A

TNF-a; IL-1b and IL-6

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82
Q

How does TLR signalling vary according to the cell type in which it occurs?

A

in specialised intestinal cells, TLR-4 induces antimicrobial peptides

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83
Q

What other name is the IKKy known as?

A

NEMO: NFkB essential modifier

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84
Q

Which pathway do the nucleic acid TLRs activate?

A

IRF family

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85
Q

Where do IRF proteins reside?

A

cytoplasm

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86
Q

What causes the activation of IRF proteins?

A

phosphorylation on serine and threonine residues in their carboxy terminus

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87
Q

What E3 ubiquitin ligase does TRIF interact with?

A

TRAF3

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88
Q

What does hte polyubinitin scaffold created by TRAF3 recruit?

A

multiprotein complex containing the kinases IKKe and TBK1 with NEMO and TANK

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89
Q

What is the function of IKKe and TBK1?

A

phosphorylates IRF3

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90
Q

What is the difference between the IRF3 response induced by TLR4 and TLR3?

A

TLR4 response is relatively weak compared with TLR3

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91
Q

Which IRF is highly expressed in plasmacytoid dendritic cells?

A

IRF7

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92
Q

What distinguishes the NOD subfamily from other NLRs?

A

amino-terminal caspase recruitment domain: CARD

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93
Q

What do NOD proteins recognise?

A

fragments of bacterial cell wall peptidoglycans

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94
Q

What does NOD1 recognise?

A

iE-DAP a breakdown product of peptidoglycans of some bacteria e.g listeria and salmonella

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95
Q

What does NOD2 recognise?

A

MDP- present in the peptidoglycans in most bacteria

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96
Q

How may NOD ligands enter the cytoplasm?

A

intracellular infection; transported from materials captured by endocytosis

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97
Q

What happens when NOD1 or NOD2 recognises its ligand?

A

recruits CARD-containing RIP2

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98
Q

Which enzymes does RIP2 associate with?

A

E3 ligases which create a polyubiquitin scaffold

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99
Q

What does the scaffold in NOD signalling recruit?

A

TAK1 and IKK which results in NfkB

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100
Q

Which cells are NOD receptors expressed in?

A

cells who are regularly exposed to bacteria- epithelial cells who form barriers; macropahges and dendritic cells

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101
Q

What is the effect of peptidoglycans from intestinal microbiota?

A

increase basal activation of neutrophisl

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102
Q

Why do mice lacking NOD1 show increased susceptibility to pathogens that lack NOD ligands?

A

loss of basal activation of neutrophils

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103
Q

Which cells strongly express NOD2?

A

in specialised epithelial cells of the small intestine

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104
Q

What is hte function of NOD2 in epithleial cells of hte gut?

A

regulates expressiong of potent antimicrobial peptides-alpha and beta defensins

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105
Q

What happens with loss of function mutations in NOD2 LRR domain?

A

impair sensing of MDP and diminshed production of defensins which weakens the natural barrier function of hte epithelium leading to inflammation

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106
Q

What disease is associated with mutations in the LRR domain of NOD2?

A

Crohns

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107
Q

What diseases are associated with gain of function mutations of NOD2?

A

early onset sarcoidosis and Blau syndrome (spontaneous inflammation)

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108
Q

What family of NLR proteins has a pyrin domain instead of a CARD domain?

A

NLRP family

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109
Q

What events stimulate NLRP3 signalling?

A

reduced intracellular potassium; generation of ROS or disruption of lysosomes

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110
Q

What can cause the loss of intracellular potassium?

A

during inefction e.g staph aureus that produce pore-forming toxins ; or death of nearby cells releasing ATP which can activate a potassium channel

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111
Q

How many ROS induced NLRP3 activation take place?

A

oxidation of a protein TRX by ROS causes it to be released from a protein it normally attached to-TXNIP. TXNIP can then displace the heat-shock caperone proteins proteins bound to NLRP3 and actiate it

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112
Q

What does NLRP3 signalling lead to?

A

formation of the inflammasome

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113
Q

What does NLRP3 activation involve?

A

aggregation of multiple monomers via their LRR and NOD domains to induce signallign

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114
Q

What does the aggregation of NLRP3 molecules cause?

A

pryin domains of NLRP3 to interact with pyrin domains of ASC

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115
Q

What is ASC?

A

an adaptor protein with a amino terminal pyrin domain and a carboxyterminal CARD domain

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116
Q

What do the CARD domains of ASC which are exposed after polymerisation interact with?

A

CARD domains of the inactive protease pro-caspase-1

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117
Q

What does the binding of pro-caspase 1 to ASC cause?

A

release of active caspase 1 fragment

118
Q

What is the function of active caspase 1?

A

ATP dependent proteoytic processing of pro-inflammatory cytokine IL-1b and IL18 and pyroptosis

119
Q

why is pyroptosis associated with inflammation?

A

release of pro-inflammatory cytokines upon cell rupture

120
Q

What must happen before inflammasome activation can produce inflammatory cytokines?

A

cells induce and translate the mRNAs that encode the pro-forms of IL-1b and IL18

121
Q

Waht can cause the induction of mRNA that encode proforms of cytokines?

A

TLR signalling

122
Q

What cells is NLRP1 expressed in?

A

monocytes and dendritic cells

123
Q

what activate NLRP1?

A

MDP as well as other factors

124
Q

What is the effect of lethal factor produced by bacillus anthracis?

A

cleaves NLRP1, which activate inflammasome and pyroptosis, killing macrophages which allows it to evade the immune system

125
Q

What does NLRC4 respond to?

A

detect various bacterial proteins that enter cells through specialised secretion systems used by pathogens to transport materials into or access nutrients from host cells

126
Q

What other proteins does NLRC4 act with?

A

NAIP2 and NAIP5

127
Q

What NLR is involved in regulating innate immunity?

A

NLRP6

128
Q

Aside from NLRs, what other proteins can cause inflammasome activation?

A

proteins of PYHIN family

129
Q

What do PYHIN proteins have in place of LRR?

A

HIN domain

130
Q

What protease does the non-canonical inflammasome used?

A

protease caspase 11

131
Q

What is the function of the non-canonical inflammasome?

A

detection of intracellular LPS

132
Q

What is significant about caspase 11?

A

is itself the detector for intracellular LPS as well as effector molecule

133
Q

What is the function of caspase 11?

A

activates pyroptosis but not processing of IL-1b or IL18

134
Q

What disease is related to inappropraite inflammasome activation?

A

gout- urate crystals activate NLRP3 inflammasome

135
Q

How do the RIG-I-like receptors bind to viral RNA?

A

using an RNA helicase-like domain in their carboxy terminal

136
Q

Waht is found at the amino-terminal domains of RLRs?

A

CARD domains

137
Q

How does RIG-I discriminate between host and viral RNA?

A

sensing differences at the 5’ end of single-stranded RNA transcripts : prokaryotes do not undergo capping

138
Q

What is the difference between RIG-I and MDA-5?

A

MDA-5 senses dsRNA, RIG-I:ssRNA

139
Q

What protein cooperates with RIG-I and MDA-5 in recognition of viral RNA?

A

LGP2

140
Q

What protein is activated by polyubiquitin chain produced by activation of RIG-I or MDA-5?

A

mitochondrial antiviral signalling protein (MAVS)

141
Q

What E3 ligases are recruited by RIG-I or MDA-5 to construct the polyubiquitin chain?

A

TRIM25 and Riplet

142
Q

What do cytosolic DNA sensors signal through to induce production of type I IFNs?

A

STING (stimulator of interferon genes)

143
Q

What is STING normally anchored to?

A

ER

144
Q

What is MAVs attached to?

A

mitochondrial membrane

145
Q

What IRF does MAVS stimulate?

A

IRF3

146
Q

How does STING sense intracellular bcaterial infection?

A

recognition of bacterial cyclic dinucleotides (CDN)

147
Q

What are CDNs?

A

bacterial second messengers produced by enzymes present in most bacterial genomes

148
Q

What does binding of CDNs to STING cause?

A

conformation change in the homodimer which recruits TBK1–IRF3

149
Q

What links TRIF, MAVS and STING?

A

contain a smilar amino acid sequence motif at their carboxy terminal which when phosphorylated recruits TBK1 and IRF3

150
Q

What does the introduction of DNA into cells generate?

A

cGAMP

151
Q

What is the function of cGAMP?

A

binds both subunits of hte STING homodimer like CDNs to induce STING signalling

152
Q

What is the enzyme that produces cGAMP in repsonse to cytosolic DNA?

A

cGAS- cyclic GAMP synthase

153
Q

What is cGAMP produced from?

A

GTP and ATP in the cytoplasm

154
Q

What infection are mice with inadequate cGAS susceptible to?

A

herpesvirus infection

155
Q

What PRRs are involved in the upregulation of B7 costimulatory moelcules?

A

TLRs

156
Q

What is B7.1 also known as?

A

CD80

157
Q

What is B7.2 also known as?

A

CD86

158
Q

What do the NLRP3s aggregate via?

A

NOD domains

159
Q

What links the procaspase 1 and ASC in inactive form?

A

CARD domains

160
Q

What is the NLRP3 inflammasome composed of?

A

NLRP3; ASC and procaspase 1

161
Q

What happens to ASC when it binds to NLRP3?

A

polymerises (as does procaspase 1) - into filamentous polymers

162
Q

What is the function of NEMO?

A

binds to the polyubiquitin chain bringing IKK complex in close proximity to TAK1

163
Q

What are TRIM25 and Riplet?

A

E3 ligases

164
Q

What is the function of activation og MAVS?

A

activates TRAFs to produce more ubiquitin chains

165
Q

what does the ubiquitin cahins in MAVS signalling recruit?

A

TBK1 and IKK complex

166
Q

How is DNA involved in cGAS converting GTP and ATP to GAMP?

A

DNA activates cGAS

167
Q

What IL is active in both its proform and cleaved forms?

A

IL-1a

168
Q

What transmembrane protein is required for IL-1R signal transduction?

A

IL1RAP (IL-1 receptor accessory protein)

169
Q

What is found in the receptor of all haematopoitin cytokines?

A

tyrosine kinases

170
Q

What 2 receptors mediate the actions of TNFa?

A

TNFR1 and TNFR2

171
Q

What cells express TNFR1?

A

wide range of cells including endothelial cells and macrophages

172
Q

What cells express TNFR2?

A

mainly lymphocytes

173
Q

What structural form are TNF-family cytokines produced as?

A

trimers

174
Q

What pathways do TNF receptors induce?

A

NFkB and PI 3-kinase

175
Q

Why is CD40 analogous to CD28 ?

A

both receptors serve to enhance Akt activation induced by the BCR or TCR

176
Q

Why do TNF receptors signal differently from antigen receptors?

A

does not involve the activation of tyrosine kinases

177
Q

What adaptor proteins do TNF receptors recruit?

A

TRAFs (TNF receptor associated factors)

178
Q

What pathway of NFkB do TNF receptors stimulate?

A

non-canonical (different to the one initiated by antigen receptors)

179
Q

What are TRAF ubiquitin ligases bound to before activation in the B cell?

A

bind cIAP and MIK

180
Q

What does the binding of TRAFs to cIAP and MIK result in?

A

ubiquitination and degradation of NIK

181
Q

What happens when CD40L is stimulated?

A

TRAF2/3; cIAP and NIK complex is recruited to CD40L

182
Q

What does the binding of CD40L to the TRAF:cIAP:NIK complex cause?

A

TRAF2 catalyses K63 ubiquitination of cIAP which then K48 ubiquitinates TRAF3 leading to its degradation and the release of NIK

183
Q

What is the function of released NIK?

A

NIK phosphorylates and activate IKKa which phosphorylates NFkB precursor protein

184
Q

What other name is NFkB precursor protein given?

A

p100

185
Q

What happens when p100 is phosphorylated?

A

it is ubiquinated and then cleaved into p52

186
Q

What does p52 bind to to form active NFkb?

A

reIB

187
Q

What activates Akt?

A

PDK1

188
Q

What happens to mice without CTLA-4?

A

die at a young age from uncontrolled proliferation of T cells in multiple organs

189
Q

What is checkpoint blockade?

A

enhancement of T cell responses by inhibiting inhibitory receptors CTLA-4 and PD-1

190
Q

When is CTLA-4 expressed on T cells?

A

after T cell activation

191
Q

What adaptor molecule is repsonsible for removing CTLA-4 from the surface membrane?

A

AP-2

192
Q

How many dimers of B7 can CTLA-4 bind?

A

2

193
Q

What happens when ITIMs or ITSMs are phosphorylated?

A

recruit inhibitory phosphatases SHP and SHIP

194
Q

How does SHP work?

A

removes phosphate groups added by tyrosine kianses to a variety of proteins

195
Q

What is the function of SHIP?

A

removes the phosphate from PIP3 to generate PIP2 reverses the recruitment of Tec kinases and Akt to the cell membrane

196
Q

Give examples of Tec family kinases?

A

Itk; Btk

197
Q

Give examples of PH domain containing ezymes which depend on their PH domain binding to PIP3?

A

Vav; Btk and PLCy

198
Q

What faily of protein kinase are the signalling chains of the haematopoietin family of cytokine recpetors noncovalently associated iwth?

A

JAK family

199
Q

What is the function of hte JAKs associated with cytokine receptors?

A

phosphorylate their associated receptors on specific tyrosine residues which recruits STATs

200
Q

What happens when cytokines bind their receptor?

A

causes dimerization of hte receptor, bringing the JAKs close together which activate each other

201
Q

What are SOCS?

A

suppressors of cytokine signalling- inhibtors that terminate the signalling of many cytokine and hormone receptors

202
Q

when are SOCS proteins induced?

A

by STAT activation- inhibit recpetor signalling after cytokine has had its effect

203
Q

Which cytokines induce acute phase responses in the liver and fever?

A

IL-1b; TNFa and IL6

204
Q

What is the difference between CC chemokines and CXC chemokines?

A

CC chemokines have 2 adjacent cysteine residues near the amino terminus whereas CXC chemokines have a single amino acid separating their cystiein residues

205
Q

What is the general function of CC chemokines?

A

migration of monocytes, lymphocytes and other cell types

206
Q

What is the general function of CXC chemokines?

A

neutrophil migration

207
Q

Aside from chemokines, what else can act as chemoattractants for neutrophils?

A

C3a, C5a and fMLF bacterial peptides

208
Q

Where are the genes for CXC chemokines found?

A

chromosome 17

209
Q

Where are the genes for CC chemokines found?

A

chromsome 4

210
Q

What marker can distinguish pDCs from cDCs?

A

pDCs express the C-type lectin BDCA2

211
Q

Apart from stimulating adhesion moleulce expression what other effect does TNFa have on endothelial cells?

A

express proteins that trigger blood clotting in local small vessels

212
Q

What cleaves TNFa to be released from its membrane-bound form into a soluble cytokine?

A

TACE

213
Q

What other name are TNFa; IL-1b and IL6 known as?

A

endogenous pyrogens

214
Q

Give an example of an exogenous pyrogen?

A

LPs

215
Q

How do endogenous pyrogens cause fever?

A

induce expression og COX2 which synthesises PG E2

216
Q

What are the effects of prostaglandin E2?

A

acts on hypothalamus to increase heat production via catabolism of brown fat and heat retention via vasoconstriction

217
Q

How do exogenous pyrogens induce fever?

A

inducing production of endogenous pyrogens or directly inducing COX2

218
Q

Why is fever generally beneficial to host defense?

A

most pathogens grow better at lower temperatures and adaptive responses are more intense at higher temperatures

219
Q

What does CRP bind to on pathogens?

A

phosphocholine portion of some bacteria and fungal cell wall lipopolytsaccharides

220
Q

What happens when CRP binds to a bacterium?

A

opsonises bacterium and activates the classical pathway

221
Q

What type of protein is MBL?

A

acute phase protein which activates lectin pathway

222
Q

Aside from CRP and MBL what other acute phase proteins are opsonins?

A

surfactant proteins SP-A and SP-D

223
Q

What is the IFN-lambda receptor composed of?

A

IL-28Ra subunit and beta subunit of hte IL-10 receptor

224
Q

What cells are type III IFN receptors expressed on?

A

epithelial cells

225
Q

What type of virus are nonmethylated CpG resiudes foudn in?

A

many DNA viruses

226
Q

What virus does deficiency of TLR9 result in susceptibility to?

A

herpes simplex

227
Q

What chemokine receptor do plasmacytoid DCs express?

A

CXCR3

228
Q

What is CXCR3 a receptor for?

A

CXCL9; CXCL10 and CXCL11

229
Q

What cell makes CXCL9, 10 and 11?

A

T cells

230
Q

What is the function of pDCs expressing CXCR3?

A

migrates from the blood into lymph nodes in which there is an ongoing inflammatory response

231
Q

How does IFNb amplify the interferon response?

A

induces cells to make IFN a

232
Q

What receptor do IFNa and IFNb bind to?

A

IFNAR

233
Q

What kinases does IFNAR use?

A

Tyk2 and Jak1

234
Q

What STATs do Tyk2 and Jak1 activate?

A

STAT1 and STAT2

235
Q

What IRF do STAT1 and STAT2 bind to?

A

IRF9

236
Q

What does the complex does the binding of STAT1 and STAT2 to IRF9 create?

A

ISGF3

237
Q

What is the function of ISGF3?

A

binds to the promoters of many interferon stimulated genes (ISGs)

238
Q

What is the function of oligoadenylate synthetase an enzyme encoded by an ISG?

A

polyermises ATP into 2’-5’ linked oligermers which activate an endoribonuclease which degrades viral DNA

239
Q

What type of enzyme is PKR?

A

serine-threonine kinase

240
Q

What is the function of PKR?

A

phosphorylates the alpha subunit of eIF2a which supppresses protein translation and contributes to the inhibition of viral replication

241
Q

What does eIF2a stand for?

A

eukaryotic initiation factor 2

242
Q

What type of enzyme are Mx1 and Mx2?

A

GTPases belonging to the dynamin protein family (IFN induced enzymes- mechanism unclear)

243
Q

How do IFIT proteins act as antiviral effector molecules?

A

inhibit steps in RNA translation- also contributes to lack of cellular proliferation induced by type I IFNs

244
Q

What is the function of IFITMs?

A

act to restrict viruses at early steps of infection by interfering with fusion of viral membranes with the lysosome membrane and late endosomes

245
Q

What viruses do IFITMs protect against?

A

Ebola virus; influenza A

246
Q

Which chemokines do IFNs induce?

A

CXCL9, 10 and 11

247
Q

What are teh general features of innate lymphoid cells?

A

have lymphoid characteristics but lack antigen specificity

248
Q

Which haematopoietic lineage do ILCs derive from?

A

common lymphocyte progenitor- lymphoid linease

249
Q

What transcription factor causes development of ILCs

A

Id2 (inhibitor of DNA binding 2)

250
Q

What cytokine do group I ILCs produce?

A

IFNy

251
Q

What stimulates group I ILCs to produce IFNy?

A

IL12 nad IL18

252
Q

What T cell subset do group I ILCs resemble?

A

Th1- use transcription factor Tbet, produce IFNy, stimualted by IL-12

253
Q

Where are ILC1 found?

A

in tissues- don’t circulate

254
Q

What cytokines do ILC2s produce?

A

IL-4, IL-5 and IL-13

255
Q

What cytokines induce ILC2s to produce cytokines?

A

thymic stromal lymphopoeitin and IL-33

256
Q

What is the function of ILC1s?

A

protection against infection by viruses or intracellular pathogens

257
Q

What is the function of ILC2s?

A

promoting mucosal and barrier immunity and iad immunity against parasites

258
Q

What cytokines do ILC3s produce?

A

IL-17 and IL-22

259
Q

What cytokines sitmualte ILC3s?

A

IL-1b and IL-23

260
Q

What is the function of ILC3s?

A

increase defenses against extracelllular bacteria and fundi

261
Q

what is the function of IL-17?

A

stimulating the production of chemokines that recruit neutrophils

262
Q

What is the function of IL-22?

A

acts on epithelial cells to the stimulate the production of antimicrobial peptides duch as RegIIIy

263
Q

What other pathway do NK cells use to kill cells apart from cytotoxic granules?

A

TRAIL which interacts DR4 and DR5 on target cells

264
Q

What happens when DR4 and DR5 are stimualted?

A

activates pro-caspase 8 and apoptosis

265
Q

What happens when antibodies bind to Fc receptors on NK cells?

A

causes them to release their cytotoxic granules- antibody-dependent cellular cytotoxicity

266
Q

What do activating receptors on NK cells respond to?

A

cell surface proteins induced on target cells by metabolic stress - stress-induced self

267
Q

What is missing self?

A

reduction in MHC-I expression

268
Q

Waht is dysregulated self?

A

changes in expression of various surface proteins on a target cells

269
Q

What adaptor do DR4 and DR5 signal via?

A

FADD

270
Q

What are the 2 large families of NK cell receptors?

A

leukocyte receptor complex and NK receptor complex

271
Q

what receptors are part of hte luekocyte receptor complex?

A

KIRs; ILT; LAIR; SIGLECs

272
Q

What chromosome are the leukocyte receptor compelx found on?

A

19

273
Q

What chromosome is the NK receptor complex fond on?

A

6

274
Q

What receptors are part of hte NK receptor complex?

A

KLRs- killer cell lectin-like

275
Q

What is the geenral feature of leukocyte receptor copmlex?

A

immunoglobulin like domaisn

276
Q

What is the difference in length between activating and inhibitory KIRs?

A

activating have short cytoplasmic tails whereas inhibitory have long tails

277
Q

Waht is the found in the tail of inhibitory KIRs?

A

ITIMs

278
Q

What is the foun in the tail of activating KIRs?

A

charged residue that associates with DAP12

279
Q

What is DAP12?

A

a transmembrane protein that has an ITAM

280
Q

What is the functiono f HLA-E?

A

instead of binding peptides derived from pathogens they bind fragments of the signal peptide derived from other MHC-I molecules during processing in the ER

281
Q

What 2 KLRs do NK cells express?

A

CD94:NKG2 heterodimerW

282
Q

What type of recptor qare the natural cytotoxicity recpeotrs?

A

activating- Ig-like

283
Q

Give examples of activating receptors?

A

natural cytotoxicity receptors; NKG2D

284
Q

What are hte ligands for NKG2D homodimer?

A

MICA; MIB and RAET1 which are MHC-like molecules expressed induced by cellualr stress

285
Q

What type of protein is NKG2D?

A

C-type lectin

286
Q

What do the activating receptors on NK cells associate with?

A

CD3xi chain; Fc receptor y chain and DAP12 which all have ITAMs

287
Q

What does NKG2D bind as a heterdoimer with CD94?

A

MHC class I moelcule HLA-E

288
Q

What is NKG2D associated with?

A

DAP10

289
Q

What does DAP10 actiate?

A

PI 3-kinase

290
Q

What is PI 3-kinase linked to in NK cells?

A

induction of cytotoxic activity

Basic Immunology- Module 1 (31 decks)

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