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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
Q

what does cd28 signaling do in naive cells

A

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.

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26
Q

true or false: the tcr -cd28 pathway ca also induce the expression of ubiquitin e3 ligase

A

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.

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27
Q

tcr antigen recognition and co stimulation: il 2 driven t cell expansion

A

-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

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28
Q

what can be used to do immunosuppression

A

-cyclosporin a blocks il2 production
-rapamycin blocks il-2r signals (mtor)

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29
Q

Turning t cell activation off: ctla-4 what happens

A

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

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30
Q

what happens to mice that do not have ctla-4

A

they suffer from a lethal disorder involvong massive lymphocyte proliferation

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31
Q

true or false: signaling nodes downstream of cd28 and tcr and icos co-stimulatory receptors do not really overlap

A

false they significantly overlap

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32
Q

true or false: cd28 recruits more effectively pi3k than icos

A

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

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33
Q

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.

A

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.

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34
Q

true or false: trafs are stimulatory

A

true

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35
Q

true or false: shp1 and shp2 are stimulatory

A

false they are inhibitory

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36
Q

what is the name of the cognate t cell/dendritic cell interactions

A

immunological synapse

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37
Q

true or false; there are different types of immunological synapses

A

true
-different stages with distinct membrane and cytoskeletal requirements

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38
Q

true or false: assembly of the immunologica synapse only occurs in one circumstance

A

false
it can occur in different circumstances for a variety of functions: t cell mobility, ag activation, granules in ctls etc

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39
Q

what are the two types of smacs

A

-periferal smac
-central smac

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40
Q

what does smac mean

A

super molecular activating complex
basically when 2 signals happened
co stimulatory, tcr/mhc and adhesion

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41
Q

what does the smac look over a period of time aka earlty to late

A

-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

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42
Q

true or false: there are lots of players in smac

A

true

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43
Q

true or false: a mature immunological synapse is requires to initiate t cell activation

A

false
it is not required
but appears to form as early as signaling is waning

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44
Q

engagement of … and … recuits lck which phosphorylates… at ITAMS

A

Engagement of TCR ligation and co-receptors, such as CD4 and CD28, recruits Lck, which
phosphorylates CD3 at immunoreceptor tyrosine-based activation motifs (ITAMs).

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45
Q

what does zap 70 binds and is activated by what

A

zap 70 binds double phosphorylated itam residues and then phosphorylated and activated by lck

46
Q

Schematic structure of the TCR signaling assembly and
immunological synapse aka them steps

A

-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
Q

immunological synapse formation: the steps

A

-t cell homing to hev
-t cell scanning for apc
-smac formation
-signal transduction and engagement of intracellular processes
-biological effector response

48
Q

what are the key chemokines for dcs to enter the lymph node

A

ccr7 and ccr8

49
Q

what are the types of exchange occuring during the synapse

A

-signals 1,2,3
-mirna
-cytokines
-stealing membranous material
-cellular attack can happen through perforins and granzimes

50
Q

t cell activation depends on 2 things:

A

-affinity of tcr and mhc
-contact duration

51
Q

true or false: the cd40l is a bidirectional signal and what does it do

A

true
-licenses aocs to activate T cells
-prolongs t cell expansion upon activation

52
Q

what plays a key role in providing the signals that orchestrate T cell differentiation

A

the cytokine environment
critical component for t cells to:
-provide a function
-migrate to the site of inflammation
-survive during the inflammation

53
Q

what induces th1, what tf induce th1 and what does it express?

A

inducer:
infy, il12, il18, il27

TF: tbet, stat 1 and stat 6

cytokines: infy, tnfa, il2

54
Q

what induces th2, what tf induce th1 and what does it express?

A

inducer: il2, il4
TF: gata3,stat5 and stat6
cytokines: il4, il5, il10, il13

55
Q

true or false: tgfb can transform a th2 cell into a th9 cell

A

true

56
Q

what induces th9, what tf induce th9 and what does it express?

A

-inducer: il4 and tgfb
-tf: gata 3 and stat6
cytokines:il-9

57
Q

what induces th17, what tf induce th17 and what does it express?

A

induver: il-6, tgfb and il23
-tf: roryt, rora and stat3
-cytokines: il-17 a and F

58
Q

what induces th22, what tf induce th22 and what does it express?

A

inducer: il6 and tnf a
tf: AHR
-cytokine: il22

59
Q

what induces fh1, what tf induce tfh and what does it express?

A

inducer: il6 and il21
tf:bcl6
-cytokine:il4,10 and infy

60
Q

what induces treg, what tf induce treg and what does it express?

A

-inducer: il2 and tgfb
tf:fox3p
-cytokine: il 10 and tgfb

61
Q

what is the main role of th1

A

cell mediated immunity
-responses to intracellular pathogens including virus, bacteria and parasites

62
Q

what is the main role of th2

A

-humoral immunity
-responses to extracellular pathogens including helminths
-allergy

63
Q

what is the main role of th17

A

extracellulat bacteria and fungi

64
Q

what is the main riole of tregs

A

tissue homeostasis

65
Q

th9 plays a role in

A

-allergic and autoimmune responses against melanoma and intestinal worms

66
Q

true or false th9 and th22 follow the activation of th2

A

true

67
Q

true or false th17 provides more affective antibacterial defense than th22 cells do

A

false
it sis the other way around, th22 slays more

68
Q

Tfh cells are required for>?

A

-for the devlopment of the germinal center
-provide il21 and cd40L signals to promote B cell survival

69
Q

true or false: both T cells and non t cells provide the third signals

A

-true because once the t cell is activated it will start to activate the other cells

70
Q

il-2 is paired with which stat

A

stat 5

71
Q

il-12 is paired with which stat

A

stat 4

72
Q

inf gamma is paired with which stat 1

A

stat 2

73
Q

Janus kinases (JAK) and Signal transducers and activators of transduction
(STATs) basically the process

A

-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
Q

what is the name of the drug that is a jak inhibitor and with who does it work

A

apoquel
only works with dogs

75
Q

tgfb is a …. signal that complememts stat 3 to generate tregs and th17 cells

A

smad signal

76
Q

which cells are at a tug of war for tgfb

A

th17 Inflammation) and tregs (homeostasis)

77
Q

true or false: tregs and th17 are mostly made in non-lymphoid organs

A

false they are made in tissues

78
Q

th1 chemokine

A

cxcr3

79
Q

th2 chemikone

A

ccr4 and ccr8

80
Q

th9 chemokine

A

ccr3. cxcr3 and ccr6

81
Q

T17 chemokine

A

ccr6

82
Q

how the differenciation of t cells is regulated

A

-immune deviation
-suppression of cytokine signaling
-epigenkc control and imprinting of gene targets
-interplay between tf

83
Q

immune deviation between th1 and th2; what happens?

A

-cytokine signals can antagonize eahother
-basically a tug of war

84
Q

what are socs

A

supressor of cytokine signalling

85
Q

what is the role of socs1 and socs3

A

socs 1 inhibits while socs 3 deinhibit

86
Q

what is the domain of the socs that binds to phosphorylated tyrosine kinases

A

sh2 domains

87
Q

socs recruit what?

A

e3 ligases and ubiquitin signalling molecules
=the proteins will be ate by a proteasome

88
Q

true or false: socs are induced bu cytokines

A

true
it is a negative feebback loop

89
Q

what are the three things that can happen in the epigenetic regulation of t cell differentiation

A

–chromatin remodeling aka opening it up
-histone modification
-dna methylation

90
Q

what opens up the dna of t cells after tcr activation, acetylation or methylation

A

-high acetylation =they are openend to polarizing signals and eacetylation makes them progress to a more specialized state

91
Q

once established, the differentiation maintains a soecific chromatin re-arrangement that allows future signals to bind to DNA at…..

A

specific location

92
Q

what do hats do and what do hdacs do

A

hats: acetylation
hdacs: deactetylation

93
Q

what happens to mice that are KO for HADC

A

-the cells can’t travel to the brain= no ms because hdac is not opening the specific locus for migration

94
Q

true or false: dna methylation stabilizes the changes

A

-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
Q

what are the enzymes that are in charge of DNA methylation

A

-dnmt: deposition of a methylated group
-ete: oxidizes the methyl group

96
Q

true or false” TF’s lowkey fight eachother

A

true

97
Q

true or false: there is plasticity in T cels

A

true

98
Q

what are the 2 origins of t regs

A

-no precise markers to differenciate
-little overlap in their tcr repertoire
-pTregs; tolerize against potential allergens
-tTregs; primary role in promoting periferal tolerance

99
Q

true or false: tregs promote inflammation and immunity

A

false; they suppress that and promote tissue homeostasis and tissue repair

100
Q

initiating the presenttaion; how do apcs decide which signals to express

A

depends on what the pathigen is lol

101
Q

true or false: salmonella can survive anti-microbial peptides

A

true

102
Q

where does salmonella multiplies

A

macrophages

103
Q

true or false: th1 cells promote cytotoxic cd4T cell responses through cd40L

A

false it is cd8

104
Q

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

A

true

105
Q

steps of the response against silly parasites

A

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
Q

th2 and th9 cells orchestrate the response; what do they do

A

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
Q

killing the parasite requires the production og iga and ige that is recognized by eosinophils

A

false it is igg and ige

108
Q

ige are key mediators of adcc against….

A

helminths they recruit eosonophils

109
Q

igg1 can also promote the release of….

A

superroxide dismutase; generate peroxide

110
Q

cytokines involved in t cell expension: what are they and what do they do

A

-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
Q

mechanism involved in the contraction of t cell expansion

A

-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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