Lecture 10 Flashcards
(114 cards)
1
Q
BCR complex
A
aIg alpha and beta CD79a and cd79b… disulfied linked to each other, non covalently linked to BCR
2
Q
Co receptors of B cells
A
CD21, 32 19
3
Q
Signalling is either…… depending on iif….. is bound
A
enhanced or inhibinited… ig beta/alpha
4
Q
Binding of Ag via receptor caues?
A
signal 1… not sufficient and may lead to anergy
5
Q
Accessory and costimulatory molecules are bound
A
signal 2
6
Q
April and Baff bind to?
A
BCMA and TACI
7
Q
BCR can be what two IG?
A
IgM or IgD
8
Q
When the Ig are class switched they become?
A
IgG, IgA, IgE
9
Q
Srk Syk activation leads to?
A
PLC gamma and RAS and RAC small GTPase
10
Q
What transcription factors does PLCgamma effect?
A
NFAT, NKkB, AP1
11
Q
These transcrtiption factors regulate?
A
cell growth, differentiation, and survival
12
Q
Srcs become active and ? can attach
A
Lyn, Fyn, Blk lipid anchors PH
13
Q
phophorlated ITAMs on alpha beta creat dock for?
A
Sh2, Syk
14
Q
Lyn, Fyn, and Blk activate?
A
Syk
15
Q
Syk phosphorlates?
A
BLNK
16
Q
THings that can be activated by BLNK?
A
RAS and Rac, PLC gamma 2, BTk
17
Q
Three pathways that can be activated?
A
RAS-MAP
PLC
PKC- beta
18
Q
BLNK recruits?
A
SOS which is the GTP/GDP exchange factor
19
Q
RAS is converted by SOS to
A
RAC that activates MAP
20
Q
Map does?
A
alteration of key proteins, changes in gene transcription
21
Q
What activates PLC gamma 2?
A
Lyn, BLNK, Syk
22
Q
PLCgamma2 hydrolyzes?
A
PIP2—> DAG and IP3
23
Q
IP3 binds to?
A
IP3R in ER and allows release of stored Ca
24
Q
What is another activated Ca channel?
A
CRAC
25
What does DAG that was activated by PIP2 do?
activates PKC and the RAS-MAP... which ultimate turns on NFkB and Ap1
26
Once Ca activation is achieved, what is the final thing activated?
NFAT
27
BRC complex
CR2, CD19, CD81
28
what can engage both CR2 and BCR?
C3d that has opsonized a microbial Ag
29
CR2 and CD 21 does what
enhances activation of B cells
30
Cleavage of 3 does what?
production of C3b and binds covalently to microbe or Ag Ab complex
31
C3b is further degraded into ?
C3d which remains bound to Ag-Ab complex
32
What binds the BCR of the the C3d fragment?
CR2
33
CR2 is expressed on?
mature Bcells with two ore more membrane proteins
34
What are the membrane boudn proteins expressed when CR2 is present?
CD19 and CD81 also called TAPA1
35
What makes up the BCR co receptor complex?
CR2-CD19-CD81
36
CR2 binding C3d brings?
CD19 proxiimity to BCR associated kinases and the CD19 tail becomes phosphorlated
37
CD19 recruits?
Lyn that applifies signal by phosphorlating ITAMs
38
CD19 also activates?
PI3
39
PI3 activates
Btk and PLC gamma 2, bc enzymes must bind to PIP3 on the inner leaflet to be fully activated... this greatly enhances teh signal
40
T and B and NK are heavily regulated btw stimulatory and inhibitory signals to controll?
collateral damage to host tissue
41
what collateral damage could occur?
uncontrolled inflammation and lymphoproliferation.. and to prevent actiavtion against self
42
Inhibitory signals are mediated by?
E3 ubiquitin ligases
43
What do inhibitroy signals recruit?
phosphatases
44
ITIMs are phosphorlated by?
Src
45
key inhibitors of B cells?
FCgammaRIIB and CD22
46
CD22 inhibits
B cells ONLY
47
FCgammaRIIB
an important attenuator of signaling activated by B cells DCs and Mo
48
ITIMs can be activated by
Src
49
P ITMs recruit
SH2
50
P ITM contains
SHP and SHIP that are SH2
51
What do SHP and SHIP do?
remove phosphates from PIP3 and inhibits PI3 activity in lymphocytes, NK, innate immune cells
52
Ubiquitin is transfered to
Lys recognized by specific E3 ubiquitin ligases
53
Lysine 48 ubiquitin chain
targets protein for degredation
54
Lysin 63
do not target for degredation.... helps non canonical NfkB
55
Canonical causes
inflammation
surfival
proliferation
56
non canonical involves
chemokines
lymphoid stroma
survival
57
characteristics of canoncial
rapid and transient
indep of protein synthesis
respond to numerous stimuli
diverse functions
58
characteristics of noncanonical
slow and persistant
dependent on protein synthesis
respond to a subset of TNFR signals
specific functions
59
Receptors in canonical
TLRs
TNFR
BCR
TCR
60
Receptors in canonical
BAFFR
CD40
LTbeta R
RANk
61
NFkB forms a family of transcrition factos
RELA, RELB, c-Rel, NF-KB1 p50, NFkB2 p52.... forms dimeric complexes
62
What sequesters IkBalpha
NF k B proteins
63
TAK1 can activate?
IKK complex mediated IkBalpha phsophorylation.... results in rapid and transient nuclear translocation of the prototypical NF k B heterodimer RELA/p50
64
non canonical relies on
p100 processing triggerd by TNFR
65
What mediates the persistnant actiavtion of RELB/p52?
NIK and IKKalpha
66
What are the precursor proteins for NFkB1 and NFkB2
p105 and p 100
| contain an Ikb LIke C terminal protion and function as NfkB inhibitors
67
P105 and p100 produces mature p50 and p52
results in disruption of IkB function of precursor proteins
68
IL 2 and TGF beta cause
FOXP3, iduced T reg cell
69
FOXP3 causes
IL10.... regulation, suppresion of inflmmatory response
70
IL6 and TGF beta
RORgammat, Th17 cell
71
RoRgammat
IL17A, IL17F, IL22
| -inflmmation
72
IL4
GATA3, Th2 cell
73
GATA3
IL4, IL5, IL13
| -allergic and helminth responses
74
IL6 IL21
BCL6, Tfh cell
75
BCL6
IL4, IL21
| -germinal centre help
76
IL12, IFNgamma
Tbet, Th1 cell
77
Tbet
IFNgamma, TNF
| -macrophage activation, inflammation
78
IL2
EOMES, cytotoxis CD4
79
EOMEs
granzyme B, perforin, FASL
| - killing of infected cell
80
complement activation
Igm
81
Fc recetor dependent phagocyte resonses; complement activation; neonatal immunity
IgG... IgG1 and 3
82
immunit agains helminths... mast cell degranulation
IgE
83
mucosal immunity
IgA
84
Cause isotype swithing to IgG1,3
CD40L, cytokines, IFNgamma
85
cause isotype switching to IgE
IL4
86
cause isotype switching to IgA
TGF beta, BAFF, others
87
WSXWS
- conserved pair of cystine residues
- X determines the specificity
type I cytokines Jak Stat hemopoietin
88
Type I cytokines
IL 2,3,4,5,6,7,9,11,12,13,15,21,23, GM CSF, GCSF
89
Type II cytokine receptors
IFNalpha beta, IFN gamma, IL10, IL 22, 20
| -intereferon receptor family
90
TNF receptor fmaily
| -some membrane bound, some soluble
TRFRI and TNFRII, CD40, Fas, TNF beta, BAFF
- preformed trimers
- mat lead to apoptosis
91
TNF receptor family types
TNF alpha, beta, LT, CD40, FasL, BAFF, APril, Ox40, GITF, nerve growth factor
92
IL1 receptor family invovle
IRAK
93
IL1 receptor family type
IL1,18,33
94
G protines
seven transmembran G protin coupled receptors
95
Cytokine binding and cluserting activates?
non recptor tyrosine kinases
96
single pass cytokines are all
beta portines
97
JAK STAT key in?
Type I and II cytokines
98
STATs are
latent transcription factos
99
STATs homo or heters....
translocate to nucleus to induce the expression of genes
100
STAT1 and STAT2 complex asccosiates with
p48
101
STAT 1 and 3
bind directly to the promoter sequence
102
MAPK activate
STAT1 and 3
103
cross linking of TNF R1 by TNF
death domain
104
Binding of addaptor protein to death domain
TRADD to death domain
105
Tradd binds to
TRAF, RIP, FADD
106
TRAF causes MAP kindase
active JNK FOS JUN to active AP1
107
AP1 and NFkB
inflammatory mediators and surviaalprotenis
108
Raf RIP Fad can also activate
active caspase 8 for apoptosis
109
Flagellin
TLR5
110
triacylated lipopetides or diacylates lipopetides
TLR 2, 1, or 2-6
111
uropathogenic bacteria
TLR11
112
LPS
TLR 4
113
IL1 also know as TLR
link to IRAK
114
IRAK links to
TRAF6, and E3 ubiquitin ligase requried for NFkB
