Lecture 10 Flashcards

1
Q

BCR complex

A

aIg alpha and beta CD79a and cd79b… disulfied linked to each other, non covalently linked to BCR

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2
Q

Co receptors of B cells

A

CD21, 32 19

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3
Q

Signalling is either…… depending on iif….. is bound

A

enhanced or inhibinited… ig beta/alpha

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4
Q

Binding of Ag via receptor caues?

A

signal 1… not sufficient and may lead to anergy

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5
Q

Accessory and costimulatory molecules are bound

A

signal 2

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6
Q

April and Baff bind to?

A

BCMA and TACI

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7
Q

BCR can be what two IG?

A

IgM or IgD

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8
Q

When the Ig are class switched they become?

A

IgG, IgA, IgE

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9
Q

Srk Syk activation leads to?

A

PLC gamma and RAS and RAC small GTPase

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10
Q

What transcription factors does PLCgamma effect?

A

NFAT, NKkB, AP1

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11
Q

These transcrtiption factors regulate?

A

cell growth, differentiation, and survival

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12
Q

Srcs become active and ? can attach

A

Lyn, Fyn, Blk lipid anchors PH

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13
Q

phophorlated ITAMs on alpha beta creat dock for?

A

Sh2, Syk

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14
Q

Lyn, Fyn, and Blk activate?

A

Syk

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15
Q

Syk phosphorlates?

A

BLNK

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16
Q

THings that can be activated by BLNK?

A

RAS and Rac, PLC gamma 2, BTk

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17
Q

Three pathways that can be activated?

A

RAS-MAP
PLC
PKC- beta

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18
Q

BLNK recruits?

A

SOS which is the GTP/GDP exchange factor

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19
Q

RAS is converted by SOS to

A

RAC that activates MAP

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20
Q

Map does?

A

alteration of key proteins, changes in gene transcription

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21
Q

What activates PLC gamma 2?

A

Lyn, BLNK, Syk

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22
Q

PLCgamma2 hydrolyzes?

A

PIP2—> DAG and IP3

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23
Q

IP3 binds to?

A

IP3R in ER and allows release of stored Ca

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24
Q

What is another activated Ca channel?

A

CRAC

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25
Q

What does DAG that was activated by PIP2 do?

A

activates PKC and the RAS-MAP… which ultimate turns on NFkB and Ap1

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26
Q

Once Ca activation is achieved, what is the final thing activated?

A

NFAT

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27
Q

BRC complex

A

CR2, CD19, CD81

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28
Q

what can engage both CR2 and BCR?

A

C3d that has opsonized a microbial Ag

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29
Q

CR2 and CD 21 does what

A

enhances activation of B cells

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30
Q

Cleavage of 3 does what?

A

production of C3b and binds covalently to microbe or Ag Ab complex

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31
Q

C3b is further degraded into ?

A

C3d which remains bound to Ag-Ab complex

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32
Q

What binds the BCR of the the C3d fragment?

A

CR2

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33
Q

CR2 is expressed on?

A

mature Bcells with two ore more membrane proteins

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34
Q

What are the membrane boudn proteins expressed when CR2 is present?

A

CD19 and CD81 also called TAPA1

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35
Q

What makes up the BCR co receptor complex?

A

CR2-CD19-CD81

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36
Q

CR2 binding C3d brings?

A

CD19 proxiimity to BCR associated kinases and the CD19 tail becomes phosphorlated

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37
Q

CD19 recruits?

A

Lyn that applifies signal by phosphorlating ITAMs

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38
Q

CD19 also activates?

A

PI3

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39
Q

PI3 activates

A

Btk and PLC gamma 2, bc enzymes must bind to PIP3 on the inner leaflet to be fully activated… this greatly enhances teh signal

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40
Q

T and B and NK are heavily regulated btw stimulatory and inhibitory signals to controll?

A

collateral damage to host tissue

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41
Q

what collateral damage could occur?

A

uncontrolled inflammation and lymphoproliferation.. and to prevent actiavtion against self

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42
Q

Inhibitory signals are mediated by?

A

E3 ubiquitin ligases

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43
Q

What do inhibitroy signals recruit?

A

phosphatases

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44
Q

ITIMs are phosphorlated by?

A

Src

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45
Q

key inhibitors of B cells?

A

FCgammaRIIB and CD22

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46
Q

CD22 inhibits

A

B cells ONLY

47
Q

FCgammaRIIB

A

an important attenuator of signaling activated by B cells DCs and Mo

48
Q

ITIMs can be activated by

A

Src

49
Q

P ITMs recruit

A

SH2

50
Q

P ITM contains

A

SHP and SHIP that are SH2

51
Q

What do SHP and SHIP do?

A

remove phosphates from PIP3 and inhibits PI3 activity in lymphocytes, NK, innate immune cells

52
Q

Ubiquitin is transfered to

A

Lys recognized by specific E3 ubiquitin ligases

53
Q

Lysine 48 ubiquitin chain

A

targets protein for degredation

54
Q

Lysin 63

A

do not target for degredation…. helps non canonical NfkB

55
Q

Canonical causes

A

inflammation
surfival
proliferation

56
Q

non canonical involves

A

chemokines
lymphoid stroma
survival

57
Q

characteristics of canoncial

A

rapid and transient
indep of protein synthesis
respond to numerous stimuli
diverse functions

58
Q

characteristics of noncanonical

A

slow and persistant
dependent on protein synthesis
respond to a subset of TNFR signals
specific functions

59
Q

Receptors in canonical

A

TLRs
TNFR
BCR
TCR

60
Q

Receptors in canonical

A

BAFFR
CD40
LTbeta R
RANk

61
Q

NFkB forms a family of transcrition factos

A

RELA, RELB, c-Rel, NF-KB1 p50, NFkB2 p52…. forms dimeric complexes

62
Q

What sequesters IkBalpha

A

NF k B proteins

63
Q

TAK1 can activate?

A

IKK complex mediated IkBalpha phsophorylation…. results in rapid and transient nuclear translocation of the prototypical NF k B heterodimer RELA/p50

64
Q

non canonical relies on

A

p100 processing triggerd by TNFR

65
Q

What mediates the persistnant actiavtion of RELB/p52?

A

NIK and IKKalpha

66
Q

What are the precursor proteins for NFkB1 and NFkB2

A

p105 and p 100

contain an Ikb LIke C terminal protion and function as NfkB inhibitors

67
Q

P105 and p100 produces mature p50 and p52

A

results in disruption of IkB function of precursor proteins

68
Q

IL 2 and TGF beta cause

A

FOXP3, iduced T reg cell

69
Q

FOXP3 causes

A

IL10…. regulation, suppresion of inflmmatory response

70
Q

IL6 and TGF beta

A

RORgammat, Th17 cell

71
Q

RoRgammat

A

IL17A, IL17F, IL22

-inflmmation

72
Q

IL4

A

GATA3, Th2 cell

73
Q

GATA3

A

IL4, IL5, IL13

-allergic and helminth responses

74
Q

IL6 IL21

A

BCL6, Tfh cell

75
Q

BCL6

A

IL4, IL21

-germinal centre help

76
Q

IL12, IFNgamma

A

Tbet, Th1 cell

77
Q

Tbet

A

IFNgamma, TNF

-macrophage activation, inflammation

78
Q

IL2

A

EOMES, cytotoxis CD4

79
Q

EOMEs

A

granzyme B, perforin, FASL

- killing of infected cell

80
Q

complement activation

A

Igm

81
Q

Fc recetor dependent phagocyte resonses; complement activation; neonatal immunity

A

IgG… IgG1 and 3

82
Q

immunit agains helminths… mast cell degranulation

A

IgE

83
Q

mucosal immunity

A

IgA

84
Q

Cause isotype swithing to IgG1,3

A

CD40L, cytokines, IFNgamma

85
Q

cause isotype switching to IgE

A

IL4

86
Q

cause isotype switching to IgA

A

TGF beta, BAFF, others

87
Q

WSXWS

  • conserved pair of cystine residues
  • X determines the specificity
A

type I cytokines Jak Stat hemopoietin

88
Q

Type I cytokines

A

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

89
Q

Type II cytokine receptors

A

IFNalpha beta, IFN gamma, IL10, IL 22, 20

-intereferon receptor family

90
Q

TNF receptor fmaily

-some membrane bound, some soluble

A

TRFRI and TNFRII, CD40, Fas, TNF beta, BAFF

  • preformed trimers
  • mat lead to apoptosis
91
Q

TNF receptor family types

A

TNF alpha, beta, LT, CD40, FasL, BAFF, APril, Ox40, GITF, nerve growth factor

92
Q

IL1 receptor family invovle

A

IRAK

93
Q

IL1 receptor family type

A

IL1,18,33

94
Q

G protines

A

seven transmembran G protin coupled receptors

95
Q

Cytokine binding and cluserting activates?

A

non recptor tyrosine kinases

96
Q

single pass cytokines are all

A

beta portines

97
Q

JAK STAT key in?

A

Type I and II cytokines

98
Q

STATs are

A

latent transcription factos

99
Q

STATs homo or heters….

A

translocate to nucleus to induce the expression of genes

100
Q

STAT1 and STAT2 complex asccosiates with

A

p48

101
Q

STAT 1 and 3

A

bind directly to the promoter sequence

102
Q

MAPK activate

A

STAT1 and 3

103
Q

cross linking of TNF R1 by TNF

A

death domain

104
Q

Binding of addaptor protein to death domain

A

TRADD to death domain

105
Q

Tradd binds to

A

TRAF, RIP, FADD

106
Q

TRAF causes MAP kindase

A

active JNK FOS JUN to active AP1

107
Q

AP1 and NFkB

A

inflammatory mediators and surviaalprotenis

108
Q

Raf RIP Fad can also activate

A

active caspase 8 for apoptosis

109
Q

Flagellin

A

TLR5

110
Q

triacylated lipopetides or diacylates lipopetides

A

TLR 2, 1, or 2-6

111
Q

uropathogenic bacteria

A

TLR11

112
Q

LPS

A

TLR 4

113
Q

IL1 also know as TLR

A

link to IRAK

114
Q

IRAK links to

A

TRAF6, and E3 ubiquitin ligase requried for NFkB