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MIMM 314 > lect 2 pici > Flashcards

lect 2 pici Flashcards

1
Q

true or false: naive t cells need access lymphoid tissue to become stimulated

A

true

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2
Q

what do memory t cells need to access

A

sites of inflammation

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3
Q

the location of t cell priming influences the induction of …..

A

peripheral homing molecules to the skin and small intestine

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4
Q

true or false: hev of t cells areas of ln are cd26l/cce7 dependant

A

true

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5
Q

stop signal for t cell migration what is it dependant on?

A

-deopendent on specific molecular patterns at the interface between t and apc
-lfa1/cam 1 dependent

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6
Q

what happens when the T cell only receives 1 signal and

A

-t cells don’t expand
-they don’t activate
-they are completely unresponsive
-cell tolerance

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7
Q

what happens when the T cells receive 2 signals

A

-firm activation with apc
-cognate interaction with apc
-t cell now undergoes t cell activation
-expansion and proliferation
-make cytokines

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8
Q

apc upregulate B7 molecules which binds on …

A

cd28 which is constitutive on T cells

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9
Q

true or false:infection, stress, cellular damage recognition by innate receptors on apc activated apcs and induce b7-1(cd80) and B7-2(cd86) expression

A

true

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10
Q

true or false: tcr or co-stimulatory signals alone are sufficient for t cell activation

A

false
-it inactivated the cells and makles the T cell anergic
=lack of il-2 production
-induction of t cell tolerance

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11
Q

t cell activation is regulated by which signals

A

-co stimulatory signals with cd40L and CD-8
-antigen specific tcr signals (this interaction occurs through a period of time)

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12
Q

true or false: cd28 is constitutive and cd80 is upragulated

A

true

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13
Q

true: cdl40 is on the tcr

A

true

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14
Q

true or false: cd40l is constitutive while cd40 is upregulated

A

false:
cd40l is up regulated while cd40 is constitutive

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15
Q

productive t cell response requite second signal: non bacterial protein antigen

A

unstimulated macrophages do not deliver a co-stimulatory signal to T cells recognizing non-bacterial antigen aka it does bot have a B7 =anergic cells

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16
Q

productive t cell response requite second signal: bacteria

A

-bacteria stimulate macrophages to delibver a co-stimulatory signal to T cells, recognizing bacterial antigen
=proliferation and deofferenciation of T cells specific for bacterial protein

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17
Q

productive t cell response requite second signal: bacterial and non-bacterial protein

A

-bacteria stimulate macrophages to deliver a co-stimulatory signal to T cells recognizing non bacterial antigen
=prolifgeration and differentiation of T cells specific for non bacterial protein

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18
Q

what does anergy mean

A

t cell activation in the absence of co-ctimulation

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19
Q

true or false: there is bi directional signalling for the second signal

A

true
once the T CELLS have become activated, they will be able to return and provide signals to the aocs=activated and katured the apc=more mhc=more co stimulatory molecules

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20
Q

true or false: cd40 occupies the top hierchiractal status by inducing upon tcr stimulation, other co stimulatory receptor of the ig and tnfr superfamilies

A

false; it is cd28

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21
Q

activation of dc cells through… is important for their activation of cd4 and cd8 t cells

A

cd40

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22
Q

what happens to the mice that are ko for cd40

A

they have very short clonal expansion upon immunization with antigen

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23
Q

what are inducible co stimulator aka icos

A

-another cd28 related molecule; induced on activated t cells
-binds icos-l expressed on activated DC, monocytes and b cells
-preferentially stimulates production of th2 cytokine, il-10

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24
Q

t cell help: licensing of apc with what?

A

cd40L/cd40 and 4-1bb/4-1bbl
this is good for optimal antiviral and antitumor immunity
-activated apc expresses cd40 and 4-1bbl which co stimulated cd8 t cells

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25
what does cd28 signaling do in naive cells
TCR/CD28 costimulation activates the IκB kinase (IKK) complex which then phosphorylates IκB, leading to its degradation and the release of Rel subunits of the NF-κB family. Free cRel translocates to the nucleus and binds to the CD28-responsive region of the Il2 gene, leading to Il2 transcription.
26
true or false: the tcr -cd28 pathway ca also induce the expression of ubiquitin e3 ligase
true The TCR-CD28 pathway can also induce expression of the ubiquitin E3 ligase, Peli1 by an uncharacterized pathway. Peli1 interacts with c-Rel and catalyzes its poly-ubiquitination (Ub), which results in degradation of c-Rel by the proteasome. This inhibits IL-2 production and results in a state of unresponsiveness known as 'T cell anergy' that is associated with peripheral T cell tolerance.
27
tcr antigen recognition and co stimulation: il 2 driven t cell expansion
-induces il-2 and high affinity il-2r(a) mrna expression -usually the re is always b and y but it is only doing moderate affinity -leads to il-2 production/expression -surface expression of il-2ra(cd25) -autocrine and paracrine il2 mediated proliferation
28
what can be used to do immunosuppression
-cyclosporin a blocks il2 production -rapamycin blocks il-2r signals (mtor)
29
Turning t cell activation off: ctla-4 what happens
ctla-4 binds more avidly B7 than cd28 does and delivers inhibitory signals to activated t cells so that the expression of cd28 is downregulated and t cell responses are supressed
30
what happens to mice that do not have ctla-4
they suffer from a lethal disorder involvong massive lymphocyte proliferation
31
true or false: signaling nodes downstream of cd28 and tcr and icos co-stimulatory receptors do not really overlap
false they significantly overlap
32
true or false: cd28 recruits more effectively pi3k than icos
false; icos is better it recruits the more active pi3k subunit p50a, thus leading to enhanced akt signalling -icos also induces il-4 through a m-maf pathway
33
Co-inhibitory signaling downstream of BTL-A, PD-1 and CTLA-4 suppresses T...... through t..... and serine/threonine protein phosphatase 2A (PP2A). These phosphatases dephosphorylate several of the major signaling nodes that are essential for co-stimulation of T cells. PD1 has also been shown to inhibit the RAS–ERK pathway.
Co-inhibitory signaling downstream of BTL-A, PD-1 and CTLA-4 suppresses T cell activation and function through the recruitment of the phosphatases SHP1, SHP2 and serine/threonine protein phosphatase 2A (PP2A). These phosphatases dephosphorylate several of the major signaling nodes that are essential for co-stimulation of T cells. PD1 has also been shown to inhibit the RAS–ERK pathway.
34
true or false: trafs are stimulatory
true
35
true or false: shp1 and shp2 are stimulatory
false they are inhibitory
36
what is the name of the cognate t cell/dendritic cell interactions
immunological synapse
37
true or false; there are different types of immunological synapses
true -different stages with distinct membrane and cytoskeletal requirements
38
true or false: assembly of the immunologica synapse only occurs in one circumstance
false it can occur in different circumstances for a variety of functions: t cell mobility, ag activation, granules in ctls etc
39
what are the two types of smacs
-periferal smac -central smac
40
what does smac mean
super molecular activating complex basically when 2 signals happened co stimulatory, tcr/mhc and adhesion
41
what does the smac look over a period of time aka earlty to late
-lfa-1/icam-1 are in the center while the tcr/mhc is in the periferal -this is called an immature psmac -later it is the other way around, the tcr/mhc is in the center while lfa-1/icam-1 is in the periferal -we call it a mature csmac
42
true or false: there are lots of players in smac
true
43
true or false: a mature immunological synapse is requires to initiate t cell activation
false it is not required but appears to form as early as signaling is waning
44
engagement of ... and ... recuits lck which phosphorylates... at ITAMS
Engagement of TCR ligation and co-receptors, such as CD4 and CD28, recruits Lck, which phosphorylates CD3 at immunoreceptor tyrosine-based activation motifs (ITAMs).
45
what does zap 70 binds and is activated by what
zap 70 binds double phosphorylated itam residues and then phosphorylated and activated by lck
46
Schematic structure of the TCR signaling assembly and immunological synapse aka them steps
-Engagement of TCR ligation and co-receptors, such as CD4 and CD28, recruits Lck, which phosphorylates CD3 at immunoreceptor tyrosine-based activation motifs (ITAMs). -ZAP70 binds double-phosphorylated ITAM residues, and then phosphorylated and activated by Lck. -LAT is recruited to the activated TCR complex and is phosphorylated by ZAP70 at several tyrosine residues on its C-terminal tail. -LAT phosphorylation induces the assembly of signaling adapters and effectors, and facilitated the formation of an extended protein network.
47
immunological synapse formation: the steps
-t cell homing to hev -t cell scanning for apc -smac formation -signal transduction and engagement of intracellular processes -biological effector response
48
what are the key chemokines for dcs to enter the lymph node
ccr7 and ccr8
49
what are the types of exchange occuring during the synapse
-signals 1,2,3 -mirna -cytokines -stealing membranous material -cellular attack can happen through perforins and granzimes
50
t cell activation depends on 2 things:
-affinity of tcr and mhc -contact duration
51
true or false: the cd40l is a bidirectional signal and what does it do
true -licenses aocs to activate T cells -prolongs t cell expansion upon activation
52
what plays a key role in providing the signals that orchestrate T cell differentiation
the cytokine environment critical component for t cells to: -provide a function -migrate to the site of inflammation -survive during the inflammation
53
what induces th1, what tf induce th1 and what does it express?
inducer: infy, il12, il18, il27 TF: tbet, stat 1 and stat 6 cytokines: infy, tnfa, il2
54
what induces th2, what tf induce th1 and what does it express?
inducer: il2, il4 TF: gata3,stat5 and stat6 cytokines: il4, il5, il10, il13
55
true or false: tgfb can transform a th2 cell into a th9 cell
true
56
what induces th9, what tf induce th9 and what does it express?
-inducer: il4 and tgfb -tf: gata 3 and stat6 cytokines:il-9
57
what induces th17, what tf induce th17 and what does it express?
induver: il-6, tgfb and il23 -tf: roryt, rora and stat3 -cytokines: il-17 a and F
58
what induces th22, what tf induce th22 and what does it express?
inducer: il6 and tnf a tf: AHR -cytokine: il22
59
what induces fh1, what tf induce tfh and what does it express?
inducer: il6 and il21 tf:bcl6 -cytokine:il4,10 and infy
60
what induces treg, what tf induce treg and what does it express?
-inducer: il2 and tgfb tf:fox3p -cytokine: il 10 and tgfb
61
what is the main role of th1
cell mediated immunity -responses to intracellular pathogens including virus, bacteria and parasites
62
what is the main role of th2
-humoral immunity -responses to extracellular pathogens including helminths -allergy
63
what is the main role of th17
extracellulat bacteria and fungi
64
what is the main riole of tregs
tissue homeostasis
65
th9 plays a role in
-allergic and autoimmune responses against melanoma and intestinal worms
66
true or false th9 and th22 follow the activation of th2
true
67
true or false th17 provides more affective antibacterial defense than th22 cells do
false it sis the other way around, th22 slays more
68
Tfh cells are required for>?
-for the devlopment of the germinal center -provide il21 and cd40L signals to promote B cell survival
69
true or false: both T cells and non t cells provide the third signals
-true because once the t cell is activated it will start to activate the other cells
70
il-2 is paired with which stat
stat 5
71
il-12 is paired with which stat
stat 4
72
inf gamma is paired with which stat 1
stat 2
73
Janus kinases (JAK) and Signal transducers and activators of transduction (STATs) basically the process
-The signal starts when a cytokine triggers the phosphorylation of JAKs by creating a conformational change between the two heterodimer receptors * JAKs then phosphorylate each other * STATs are recruited to the JAKs and undergo phosphorylation that activates them and makes then homodimerize* * Activated STATs can then go to the nucleus and engage DNA binding
74
what is the name of the drug that is a jak inhibitor and with who does it work
apoquel only works with dogs
75
tgfb is a .... signal that complememts stat 3 to generate tregs and th17 cells
smad signal
76
which cells are at a tug of war for tgfb
th17 Inflammation) and tregs (homeostasis)
77
true or false: tregs and th17 are mostly made in non-lymphoid organs
false they are made in tissues
78
th1 chemokine
cxcr3
79
th2 chemikone
ccr4 and ccr8
80
th9 chemokine
ccr3. cxcr3 and ccr6
81
T17 chemokine
ccr6
82
how the differenciation of t cells is regulated
-immune deviation -suppression of cytokine signaling -epigenkc control and imprinting of gene targets -interplay between tf
83
immune deviation between th1 and th2; what happens?
-cytokine signals can antagonize eahother -basically a tug of war
84
what are socs
supressor of cytokine signalling
85
what is the role of socs1 and socs3
socs 1 inhibits while socs 3 deinhibit
86
what is the domain of the socs that binds to phosphorylated tyrosine kinases
sh2 domains
87
socs recruit what?
e3 ligases and ubiquitin signalling molecules =the proteins will be ate by a proteasome
88
true or false: socs are induced bu cytokines
true it is a negative feebback loop
89
what are the three things that can happen in the epigenetic regulation of t cell differentiation
--chromatin remodeling aka opening it up -histone modification -dna methylation
90
what opens up the dna of t cells after tcr activation, acetylation or methylation
-high acetylation =they are openend to polarizing signals and eacetylation makes them progress to a more specialized state
91
once established, the differentiation maintains a soecific chromatin re-arrangement that allows future signals to bind to DNA at.....
specific location
92
what do hats do and what do hdacs do
hats: acetylation hdacs: deactetylation
93
what happens to mice that are KO for HADC
-the cells can't travel to the brain= no ms because hdac is not opening the specific locus for migration
94
true or false: dna methylation stabilizes the changes
-true -the methyl group is covalently linked to the DNA the more there is on the DNA, the less ability to transcrive that specific DNA -this happens through enzymes
95
what are the enzymes that are in charge of DNA methylation
-dnmt: deposition of a methylated group -ete: oxidizes the methyl group
96
true or false" TF's lowkey fight eachother
true
97
true or false: there is plasticity in T cels
true
98
what are the 2 origins of t regs
-no precise markers to differenciate -little overlap in their tcr repertoire -pTregs; tolerize against potential allergens -tTregs; primary role in promoting periferal tolerance
99
true or false: tregs promote inflammation and immunity
false; they suppress that and promote tissue homeostasis and tissue repair
100
initiating the presenttaion; how do apcs decide which signals to express
depends on what the pathigen is lol
101
true or false: salmonella can survive anti-microbial peptides
true
102
where does salmonella multiplies
macrophages
103
true or false: th1 cells promote cytotoxic cd4T cell responses through cd40L
false it is cd8
104
true or false; other t cells can always help fighting an infection, it does not to always have to be one type of t cell
true
105
steps of the response against silly parasites
induction phase: -implantationphase -virulence factors by the parasite favor tolerance over inflammation -migration; change of parasite stage effector phase -antigen specific response -th2/th9 cells -b cell maturation and release of ige
106
th2 and th9 cells orchestrate the response; what do they do
th2 cells; -il4; polarization of th2 antibody production -il13; antibody production, mucus secretion -il-5; eosinophil recruitment th9 cells: mastocyte activation -histamine; vasodilation and migration of immune cells -ige and igg; mac, mastocyte degranulation and eosonopji; activation
107
killing the parasite requires the production og iga and ige that is recognized by eosinophils
false it is igg and ige
108
ige are key mediators of adcc against....
helminths they recruit eosonophils
109
igg1 can also promote the release of....
superroxide dismutase; generate peroxide
110
cytokines involved in t cell expension: what are they and what do they do
-il7; critical for the survival of naive or memory t cells -il2 criticql for the expansion of effector t cells -il15; important for both t cell survival and expansion (stat 5) also involved in memory t cell survival
111
mechanism involved in the contraction of t cell expansion
-decrease the abindance of cytokines that promote expansion like il2 and il5 -prolonged tcr engagement : apoptosis, energy from neglect and expression of inhibitory receptors -active suppressive mechanisms like t regs

MIMM 314 (11 decks)

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