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immunology > 9: Immune receptors and Signal Transduction 2 > Flashcards

9: Immune receptors and Signal Transduction 2 Flashcards

1
Q

what are BCRs

A

transmembrane form of an antibody

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2
Q

what antibodies are expressed by naive mature B cells

A

IgM and igD

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3
Q

how are antibodies other than IgM and IgD expressed on B cells

A

class switching or with memory cells

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4
Q

what are the signaling molecules for BCR

A

Iga and IgBeta

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5
Q

how are Ig a and IgB linked

A

disulfide bonds to each other and noncovalent with BCR

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6
Q

what makes Iga and IgB signaling molecules

A

have ITAMS in cytoplasmic tails

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7
Q

what is better about BCR compared to TCR

A

has two binding sites

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8
Q

co- receptors for B cells that associate with BCR complex

A

CD21, CD32, CD 19

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9
Q

which co receptors positively regulate B cell activation

A

CD21 and 19

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10
Q

What does CD 32 do for B cell activation

A

has an ITIM for negative regulation of BCR

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11
Q

how do the coreceptors link for BCR

A

to antibody Fc portion or through complement

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12
Q

Another name for CD 32

A

FcyRII

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13
Q

signal one for BCR complex

A

Ag to Ig receptor

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14
Q

signal 2 for BCR

A

CD 19, 21, 32 for signal 2 and signal transduction

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15
Q

what initiates B cell signaling and what does it cause

A

BCR- Iga/B complex with phosphorylation of ITAMS

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16
Q

what happens after ITAM phosphorylation in BCR

A

activation kinases and phosphatases

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17
Q

what controls the cascade of signals from B cell activation

A

co-receptors

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18
Q

what is the role of second messengers in BCR

A

activate TFs for effector function

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19
Q

what is effector function of BCR

A

Ab production

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20
Q

TcFs change B cells from

A

naive to mature/ active cells

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21
Q

what is activated by Ag binding to a BCR complex

A

Src-Syk activation

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22
Q

how must ag bind to BCR complex

A

As cross linked dimers

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23
Q

what is activated by 2 Src- 1 syk activation

A

PLCy and RAS/ RAC GTP

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24
Q

what transcription factors are activated as a result of BCR activation

A

NFAT, NF-kB and AP1

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25
Q

what do activated PLCy and RAS turn on in B cell activation

A

genes for Cell growth, differentiation and survival

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26
Q

what activates Syk in BCR

A

SRC phosphorylates ITAM of Iga and Ig B that allows SYK activation with SH2 domains

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27
Q

What is activiated by Syk specificaly

A

PLCy that in turn activates Grb2/SOS thorugh SLP 65

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28
Q

NFAT means

A

nuclear factor activate T cells

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29
Q

what are examples of Src kinases

A

Lyn, Fyn, and Blk

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30
Q

what connects Src kinases to plasma membrane

A

lipid anchors

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31
Q

where do cross liked BCRS go for adaptors and signaling molecules

A

lipid rafts

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32
Q

what type of domains do Syk kinases have

A

SH2

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33
Q

what activates Syk tyrosine kinases

A

Src kinases

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34
Q

what is activated by Syk

A

BLNK and other adaptor proteins

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35
Q

besides RAS, RAC and PLCy, what else is activated by SYK

A

BTK, bruton tyrosine kinases.

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36
Q

what pathways do BRC activate

A

Ras-MAP, PLC and PKC-B

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37
Q

what does IP3 bind to release Ca2+ from ER

A

IP3R receptor

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38
Q

PLCy activated by Syk leads to

A

PIP2 hydrolyzed into DAG and IP3

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39
Q

DAG leads to

A

PKC activation for RAS-MAP resulting in AP-1 and NF-kB

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40
Q

what happens after Ca2+ reaches the level it needs

A

activates calmodulin-calcineurin pathways

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41
Q

what does calmodulin-calcineurin activate

A

NFAT

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42
Q

how do TCR and BCR compare

A

same end result but different starts

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43
Q

what is needed for B cell activation of complement

A

a complex of CR2, CD 19, and CD 81

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44
Q

what part of complement binds and how

A

C3d bound to bacteria binds CR2 while the bacteria binds IgM with an antigen

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45
Q

what does the combo of BCR and CR2 complex lead to

A

enhance B cell activation

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46
Q

what is another name for CR2

A

CD 21

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47
Q

complement activation is part of what type of immunity

A

innate immunity

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48
Q

how does C3d become involved with the BCR complex

A

C3 is cleaved by C3b that binds the microbe then degrades into C3d that remains bound to microbe

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49
Q

BCR recognizes what part of the microbe

A

Ag

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50
Q

what part of the microbe does CR2 recognize

A

C3d

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51
Q

what makes up the B cell co-receptor complex

A

CR2-CD19- CD 81

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52
Q

what does the binding of Cr2 and C3d cause

A

CD 19 gets moved close to BCR associated kinases

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53
Q

what do BCR kinases do to CD19

A

phosphorylate the tyrosines

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54
Q

why are do the tails of CD 19 need to be phosphorylated in BCR activation

A

recruits lyn to amplify BCR so ITAMS of Iga and IgB can be phosphorylated

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55
Q

what does phosphorylated CD 19 activate

A

Pi3 kinase

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56
Q

what does PI3 kinase do

A

activates Btk and PLCy for greater activation of B cells

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57
Q

what is important for the immune system to work properly

A

balance between stimulatory and inhibitory signals

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58
Q

why is B cell activation so tightly controlled

A

avoid collateral damage in host tissue

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59
Q

what happens without inhibition

A

uncontrolled inflammation and lymphoproliferation that could lead to self antigens

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60
Q

what runs the inhibitory signaling of lymphocytes

A

inhibitory receptors and E3 ubiquitin ligases

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61
Q

what is the role of inhibitory receptors

A

recruit and activate phosphatases to counter kinases from Ag receptors

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62
Q

what are immune cells that have the biggest need for inhibition

A

NK cells, T cells and B cells

63
Q

what are the parts of inhibitory receptor

A

ligand binding and ITIM on cytosolic tail

64
Q

what happens when ligands bind inhibitory receptor

A

ITIM phosphorylated by SRC kinases

65
Q

what does this phosphorylation of ITIMS result in

A

SH2 domains with tyrosine phosphatase bind for activation and lead to the dephosphorylation of substrates.

66
Q

key B cell inhibitory receptors

A

FcyRIIB and CD 22

67
Q

what does FcyRIIB cause

A

attenuation of signaling in activated B cells, DCs and macrophages

68
Q

what is CD 22 an inhibitor for

A

B cells only.

69
Q

two common phosphatases recruited by pITIMs

A

SHP and SHIP

70
Q

what is SHP

A

SH2 domain containing phosphatases

71
Q

what is SHIP

A

SH2 domain containingh inositol phosphatases

72
Q

what is one of the main molecules that SHP and SHIP work on

A

PIP3 to inhibit PI3 kinase activity

73
Q

what types of cells does PI3 kinase work with

A

lymphocytes, NK, and innate immune cells

74
Q

what is ubiquitin

A

protein that is transferred to lysine residues based on E3 u ligases

75
Q

how does ubiquination usually happen

A

poly ubiquitin chain by multiple ubiquitins

76
Q

what is important for a ubiquitin chain

A

the shape and depends on which lysine residue was targeted.

77
Q

what does lysine 48 ubiquitin chain lead to

A

proteasome degradation

78
Q

lysine 63 leads to

A

no degradation

79
Q

what is E3 ubiquitin ligases important for

A

non-canonical NF-kB signaling.

80
Q

what leads to production of T reg cells

A

IL2 and TGFB

81
Q

what leads to TH17

A

IL6 and TGF B

82
Q

what leads to TH2

A

IL4

83
Q

what leads to TFH cell production

A

IL6, IL 21, TH1, TH2, TH17

84
Q

what leads to T H1 cell prodution

A

IL12, IFNy

85
Q

what is the effector mediators for T reg cells

A

IL 10

86
Q

what does IL 10 cause

A

regulation and suppression of inflammatory response

87
Q

what results from Th17 cells

A

IL 17 A, F, and IL22

88
Q

what are IL 17 A, 17 F, and IL22 for

A

inflammation

89
Q

what do TH2 cells lead to

A

IL 4, 5, 13

90
Q

what is the role of Il 4,5, 13

A

allergic and helminth response

91
Q

What is produced by TFH cells

A

IL 4 and 21

92
Q

what is the role of IL4 and 21

A

Germinal centre help

93
Q

what is produced by TH1

A

IFNy and TNF

94
Q

what are IFN and TNF responsible for

A

macrophage activation and inflammation

95
Q

what cytokines lead to class switching to IgG

A

IFNy

96
Q

what Cytokine leads to IgE

A

IL4

97
Q

what leads to IgA

A

cytokines produced in mucous tissue such as TGF B and Baff

98
Q

what is IgM for

A

compliment activatioin

99
Q

what is IG 1 and 3 for

A

Fc receptor dependent phagocytes, compliment and neonatal placental transfer immunity

100
Q

what is Ig E for

A

helminth immunity or allergies, Mast Cell degradation for hypersensitivity

101
Q

what is IgA for

A

mucosal immunity

102
Q

what is the structure of cytokine receptors

A

transmembrane proteins with EC domain for cytokine binding and tail for signaling

103
Q

what activates signaling pathways for cytokine receptors

A

ligand- induced receptor clustering

104
Q

what does cytokine binding and clustering activate

A

non-receptor tyrosine kinases

105
Q

what is the classification of cytokine receptors based on

A

structural homologies, cytokine binding and shared intracellular signaling domains

106
Q

how many classes of cytokine receptors are there

A

5

107
Q

what are the 5 classes of cytokine receptors

A

Type I, Type II, Chemokine, TNF, IL1

108
Q

what is different about chemokine receptors compared to others

A

has more than a single pass transmembrane protein

109
Q

example of type I cytokine receptor

A

Jak STAT

110
Q

ligands for type 1

A

IL 2, 3, 4, 5, 6, 7, 9, 11, 12, 13,15, 21, 23, GMCSF, G CSF

111
Q

ligand of type 2

A

IFN a/b/y, IL 10 and 22

112
Q

ligands for TNF

A

TNF a, B, LT, CD 40, FasL, BAFF, April, Ox40, GITR, nerve growth factor

113
Q

ligand for IL1 receptor

A

IL 1, 18, 33

114
Q

describe a type 1 receptor

A

unique ligand binding chains, one or more signal tranducing chains shared by several receptors for different cytokines

115
Q

subgroups of type I cytokines are due to

A

shared signaling domains

116
Q

what are the key players in Type I and type II cytokine receptors

A

JAK STAT

117
Q

what does STAT stand for

A

signal transducers and activators of Tc

118
Q

what does JAK stand for

A

Janus Kinases

119
Q

what is the role of JAK

A

phosphorylates tyrosines on STAT

120
Q

what type of TF are STATs

A

latent TFS that translocate to nucleus to induce gene expression

121
Q

structure of JAK and STAT pinding

A

homo or heterodimers

122
Q

what is also activated for STAT

A

MAPK pathway

123
Q

how are MAPK and STATs related

A

MAP K phosphorylates Serine residues in STAT 1 and 3 to enhance their Tc activity

124
Q

another name for type II receptors

A

interferon receptors

125
Q

structure of type II

A

one ligand binding chain and one signaling chain

126
Q

what signaling is used by Type II

A

JAK-STAT alone or JAK STAT with Tyk-STAT

127
Q

TNF receptor structure

A

trimer

128
Q

what can TNF receptors cause

A

gene expression or apoptosis

129
Q

most important TNF receptors

A

TNFR1, TNFRII, CD40, Fas, TNF-B receptor and BAFF receptor

130
Q

ligands of TNF receptors are

A

formed in trimers and can be membrane bound or soluble

131
Q

what can be activated by TNF receptors

A

NF-kB and MAP Kinase or apoptosis

132
Q

what is BAFF

A

B cell activating factor

133
Q

TNF receptor bound by ligand leads to

A

TRADD adaptor protein binding to activate TRAF, E3, and RIP1 kinase

134
Q

What MAP kinase pathway is activated by TRAF

A

JNK to FOS for AP1

135
Q

what is activated by TRAF for apoptosis

A

Caspase 8

136
Q

Another name for TNF receptors

A

CD 40

137
Q

structure of IL1 receptor family or TLRs

A

conserved cytosolic sequence with TIR domain

138
Q

TIR means

A

Toll-like/ IL 1 receptor domain

139
Q

what happens when TLRs are active

A

receptor dimerization or recruitment of one or more of 4 adaptor proteins to TIR

140
Q

What to TIR adaptors do

A

Link the TLR to IRAK

141
Q

IRAK means

A

IL-1R associated kinases

142
Q

what does IRAK do w/ TLR

A

links adaptors to TRAF6

143
Q

what is TRAF6

A

E3 ligase needed for NF-kB activation

144
Q

what is also signaled by TLRs

A

MAP kinase activation, phosphorylation of IRF3 aand 7

145
Q

IRF3 means

A

interferon regulatory factor

146
Q

what do IRF 3 and 7 do

A

induce type I interferon Tc

147
Q

what happens when chemokines bind their receptor

A

adhesion, migration, chemotaxis, change shape, reorganize cytoskeleton, up regulate integrin expression, integrin activation

148
Q

what is usually used with chemokine receptors

A

GPCR for G protein activation as chemoattractant

149
Q

what is activated by GPCR in chemokine signaling

A

Ras and PLCy

150
Q

what does RAS lead to

A

Protein K B

151
Q

what does PLCy lead to

A

PKC

152
Q

what is inhibited by GPCR

A

cAMP concentration and production

153
Q

What inhibits adenylyl cyclase for reduced cAMP by GPCR

A

alpha subunit

154
Q

what activates RAS and PLCy

A

By complex

immunology (10 decks)

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