T Cell and B Cell Activation and Signaling Flashcards

1
Q

To activate naive T cells

A
  1. TCR
  2. Costimulatory
  3. Cytokine signaling
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2
Q

CD4+ T helper cells antigen interaction

A

Via TCR with antigen peptide complexed with class II MHC on antigen presenting cell

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3
Q

CD8+ T cytotoxic cells antigen interaction

A

TCR interaction with antigenic peptide bound to class I MHC on target cell

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4
Q

CD4+ T helper cell activation

A

Essential for development of cell-mediated immunity and optimal humeral immunity

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5
Q

TCR receptor signaling

A

Engagement by peptide/MHC initiates multiple pathways

Regulated by activation/inhibition of protein kinases/phosphatases and amplified by cascades

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6
Q

Costimulatory signaling

A

CD28 interacting with B7 family members (CD80/CD86) on antigen presenting cells
Acts synergistically with TCR signaling to enhance gene transcription and stabilize cytokine mRNA

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7
Q

Cytokine signaling

A

Antigen presenting cell makes cytokines or autocrine signaling (to provoke making of transcription factors)

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8
Q

Immediate gene expression

A

Within 30 min of TCR signaling

ie. TF

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9
Q

Early gene expression

A

1-6h of TCR signaling

ie. Cytokines

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10
Q

Late gene expression

A

More than 2 days after TCR signaling

ie. Adhesion molecules

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11
Q

IL-2

A

T cell growth factor

Allows autocrine growth, cell cycle progression and differentiation into memory and effector cells

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12
Q

GM-CSF

A

Neutrophil production

First line of defence against bacteria

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13
Q

Major events of TCR signaling

A
Phospholipase Cgamma activation
Increase in intracellular Ca concentrations
Protein kinase C activation
Nuclear translocation of NFkappaB
Activation of Ras/MAPK pathway
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14
Q

Receptors/AP involved in TCR signaling

A

TCR/CD3 complex, CD4, CD8 coreceptors

Accessory molecules CD2, CD28, CD45

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15
Q

CD45

A

(T cell signaling)
Cell surface phosphatase that catalyzes the dephosphorylation of inhibitory tyrosine residue on p56lck
Causes activation and phosphorylation of CD3 ITAMs and phospholipase Cgamma

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16
Q

Calcium release

A

Ca released with 1 TCR

Max release with 10+ TCR

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17
Q

p56lck

A

(T cell signaling)
CD4/CD8 associated protein tyrosine kinase
Sequestered into lipid rafts (that exclude TCR/CD3) in resting T cell
TCR engangement recruits TCR/CD3 complex into lipid rafts and CD4/CD8 coreceptors that interact with invariant regions of the MHC molecule form clusters
Phosphorylates the ITAMs located on 4 chains of CD3 complex

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18
Q

SMAC

A

Central and peripheral
Immunological synapse formed by sequestering TCR/CD3 into lipid raft
TCR/CD3 complex molecules on the inside and adhesion molecules on the outside

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19
Q

pSMAC

A

CD2 on T cell interacting with LFA-3

LFA-1 on T cell interacting with ICAM-1

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20
Q

cSMAC

A

TCR/CD3 interacting with MHC
p56lck
CD4/CD8 interacting with MHC

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21
Q

ITAMs (T cell)

A

Located on zeta, gamma, delta and epsilon chains of the CD3 complex

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22
Q

zeta Chain of CD3

A

(T cell signaling)
Phosphorylated by p56lck
Homodimer forms docking sites for protein tyrosine kinase ZAP70, which memes activated

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23
Q

ZAP70

A

(T cell signaling)
Associated with zeta chain of CD3 to become activated
Phosphorylates membrane associated adaptor proteins (Vav1, Shc, LAT, SLP76) that act as scaffolds for the recruitment of other molecules in signal transduction

24
Q

Vav1

A

(T cell signaling)
Membrane associated adaptor protein that acts as scaffold for recruitment of other molecules in signal transduction
Phosphorylated by ZAP70

25
Q

Shc

A

(T cell signaling)
Membrane associated adaptor protein that acts as scaffold for recruitment of other molecules in signal transduction
Phosphorylated by ZAP70

26
Q

LAT

A

(T cell signaling)
Membrane associated adaptor protein that acs as scaffold for recruitment of other molecules in signal transduction
Phosphorylated by ZAP70
Phospholipase Cgamma docks and becomes phosphorylated and activated

27
Q

SLP76

A

(T cell signaling)
Membrane associated adaptor protein that acs as scaffold for recruitment of other molecules in signal transduction
Phosphorylated by ZAP70

28
Q

Phospholipase Cgamma

A

(T cell signaling)
Docks to LAT and becomes phosphorylated/activated
Hydrolyzes membrane associated phosphoinotisol bisphosphate to generate IP3 and DAG

29
Q

Ionistol 1,4,5-triphosphate (IP3)

A

(T cell signaling)
Result of hydrolysis of phosphoinotisol bisphophate by phospholipase Cgamma
Causes Ca released from ER
Causes opening of Ca channels in cell membrane

30
Q

NFAT

A

(T cell signaling)
Dephosphorylated by calcineurin, which is activated by increase Ca levels caused by IP3
NFAT translocated to the nucleus where it causes transcription of cytokines including IL2 and IL4

31
Q

DAG

A

(T cell signaling)
Byproduct of hydrolysis of phosphoinotisol bisphosphate by phospholipase Cgamma
Activates PKC

32
Q

Protein kinase C

A

(T cell signaling)
Activated by DAG
Translocates to lipid rafts
Phosphorylates serine and threonine residues
Initiating cascade of signaling events that cause activation of NFkappaB

33
Q

NFkappa B

A

(T cell signaling)
Usually kept inactive by IkappaB
Activation of IKK allows phosphorylation of IkappaB causing NFkappaB
Promotes transcription of IL2

34
Q

RAS

A

(T cell signaling)
Small G protein
Activated by GTP following TCR-CD3 signaling
Leads to activation of MAPK pathway, including MAPK ERK

35
Q

ERK

A

(T cell signaling)
Activated by Ras activated MAPK pathway
Activates transcription factor Elk that induces Fos expression
Phosphorylates Fos, which combines with Jun to form transcription factor AP1 involved in regulating IL2 gene transcription

36
Q

AP1

A

(T cell signaling)
Phosphorylated Fos + Phosphorylated Jun
Involved in regulating IL2 gene transcription

37
Q

CD28

A

Present on surface of resting and activated T cells as disulphide linked homodimer
Interacts with B7 family members from APC

38
Q

B7 family

A

B7-1 (CD80) and B7-2 (CD86)

Found on dendritic cells, activated macrophages and activated B cells

39
Q

Cytokine mRNA

A

Usually very unstable to regulate inappropriate immune response and potential auto reactivity

40
Q

Negative Costimulatory signaling

A
Only in activated T cells
Using CTLA4 (CD152)
41
Q

CTLA4

A

Found only on activated T cells
Structurally similar to CD28, binds to B7 family members but provides inhibitory signal to down-regulate T cell activation
Induced within 24h of TCR engagement and has a higher affinity for B7 molecules than CD28
Expression is proportional to strength of CD28 signalling, allowing for correct amount of regulatory braking

42
Q

PD-1

A

Interacts with PD-L1 and PD-L2

Inhibits T cell activation

43
Q

B cell signaling

A

mIg engagement and cross linking by antigen
Initiates Src kinase, which phosphorylates ITAMs of Ig-alpha and Ig-beta
ITAMs are docking sites for Syk

44
Q

Src kinase

A

(B cell signaling)
Initiated by cross linking of mIg of B cell with antigen
Phosphorylates ITAMs of Ig-alpha and Ig-beta
ITAMs are docking sites for Syk

45
Q

Syk

A

(B cell signaling)
Phosphorylated by docking on ITAMs of Ig-alpha and Ig-beta
Phosphorylates adaptor protein BLK

46
Q

BLK

A

(B cell signaling)
Phosphorylated by Syk
Docking site of PLCgamma2 and Bruton’s tyrosine kinase (BtK)
Causes induction of multiple signaling pathways that culminate in the activation of transcription factors

47
Q

B Cell coreceptors

A

Complex of CD19, CR2 and TAPA-1

48
Q

CD19

A

Part of B cell coreceptors

Long cytoplasmic tail that has docking sites of intracellular molecules, such as PTK lyn

49
Q

Lyn

A

Protein tyrosine kinase

Augments signals delivered by the BCR

50
Q

CR2

A

Part of BC coreceptors

Interacts with C3d

51
Q

C3d

A

Formed by C3b cleaved by Factor I

52
Q

CD22

A

Part of BC coreceptors
Constitutively associated with BCR
Following activation, delivers negative signal due to tyrosine phosphatase SHP-1 bound to ITIM

53
Q

SHP-1

A

Bound to ITIM on CD22

Delivers negative signal following activation of BCR

54
Q

ITIM

A

On cytoplasmic tail of CD22

Binds SHP-1

55
Q

Clonalanergy

A

State of unresponsiveness
CD4+/CD8+ T cells that receive signal through TCR/CD3 complex that fail to receive costimulatory signal
Unable to respond to antigenic peptide
Alterations in key components of TCR signaling pathways