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Immunology > 12 - Lymphocyte Activation and Differentiation > Flashcards

12 - Lymphocyte Activation and Differentiation Flashcards

1
Q

What are the 2 effector forms T-cells differentiate to?

A

CD8+ CTLs | CD4+ Th cells

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2
Q

What is the T-cell activation stage?

A

naive T-cells recognize cognate antigen in secondary lymphoid tissues resulting in effector and memory T-cells

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3
Q

What are memory T-cells? Where do they reside?

A

ready to undergo clonal expansion when it comes into contact with cognate antigen again | basis of vaccination | at site of primary infection

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4
Q

What are the 3 signals needed to fully activate T-cell army which will undergo expansion? What are these signals needed for?

A

TCR engagement (for activation) | co-stimulation (for activation) | cytokine signaling (for expansion, IL2)

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5
Q

What is an immunological synapse? What do the proteins involve ensure?

A

when APC and T-cell come together along with all of the proteins necessary for activation = ensures interaction remains constant for enough time to fully activate the T-cell (lipid rafts bring proteins togther)

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6
Q

Which co-receptor mediates the first signal: TCR engagement?

A

CD3

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7
Q

What does CD3 have that TCRs do not have?

A

cytosolic signaling molecules such as ITAM and ITIM

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8
Q

What role does CD4/CD8 have on TCR engagement?

A

activates Lck

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9
Q

What is Lck?

A

tyrosine kinase | activates ITAM regions on CD3

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10
Q

In TCR engagement, what does the activation of ITAM regions lead to?

A

turns on transcription factor of a certain gene needed to be expressed

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11
Q

What is CD28? What is it needed for?

A

homodimer co-stimulatory receptor expressed on naive T-cells | enhances TCR-induced proliferation and survival, activates naive T-cells

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12
Q

What are the 2 ligands of CD28? Where are these expressed?

A

CD80 (on T-cells and APCs) and CD86 (only on APCs)

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13
Q

If you wanted to activate T-cell in vitro, what could you do?

A

1st signal = use anti-CD3 antibody to make T-cell think it is interacting with MHC molecule | 2nd signal = use anti-CD8 antibody

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14
Q

What is the function of negative costimulatory receptors in T-cell activation?

A

helps turn activation off

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15
Q

What are the 2 ways in which negative co-stimulation occurs?

A

CTLA-4 and clonal anergy

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16
Q

What is CTLA-4?

A

shuts down T-cell activation pathways and binds to CD28

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17
Q

How can clonal anergy cause negative costimulation in T-cell activation?

A

when second signal (costimulatory) is absent

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18
Q

What is the role of APCs?

A

express the co-stimulatory molecule to activate T-cells (no other cells can do this, just APCs)

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19
Q

What is the cytokine IL2?

A

autocrine cytokine | induces lymphocytes to expand | upregulates IL-2R so that it can undergo proliferation/expansion itself

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20
Q

What do the cytokines that the APCs secrete dictate?

A

outcome of T-cell activation = what type of T-cell we get

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21
Q

What is telling the APC what polarizingcytokines to produce? What turned on those cytokines or genes encoding for it in the APC?

A

PRR signaling - what PRR is activated = affect which polarizing cytokines APC will produce = affects the type of Th subset we get

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22
Q

What are polarizing cytokines?

A

produced by APCs, dictates which Th cell a naive T-cell will be

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23
Q

In which stage during T-cell activation does the naive T-cell differentiate into a specific subset?

A

differentiation stage

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24
Q

What are the 3 things that initial activation signals 1 and 2 induce?

A

upregulation of pro-survival genes (ie: Bcl-2) | transcription of IL2 and IL2R (CD25) | activation/proliferation of memory and effector T-cells

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25
Q

What is the role of polarizing cytokines?

A

cause the mature naive T-cell to undergo differentiation

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26
Q

Where are polarizing cytokines secreted from?

A

APCs

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27
Q

What do polarizing cytokines induce?

A

induces expression of master gene regulator

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28
Q

What is a master gene regulator?

A

regulates expression of certain effector cytokines

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29
Q

What pathway is involved in T-cell differentiation?

A

JAK/STAT pathway

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30
Q

What are the 4 effector functions of T-reg cells?

A

suppress immune response | causes anergy | turns off cytokine production | turns off effector cell function in other T-cells

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31
Q

What is the role in disease of T-reg cells?

A

helps induce tumor responses (bad) | inhibits autoimmunity

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32
Q

What are the 2 effector functions of Th17 cells?

A

fights extracellular pathogens (bacteria and fungi) | establishes barriers (ie: mucosal)

33
Q

What are the 2 roles in disease of Th17 cells?

A

autoimmunity | tissue proinflammatory

34
Q

What are the 2 effector functions of Th2 cells?

A

fights parasites (ie: worms) | activates eosinophils

35
Q

What is the role in disease of Th2 cells?

36
Q

What are the 3 effector functions of Tfh cells?

A

regulate humoral immunity (B-cells) = ensures B-cells undergo class-switching | help B-cell proliferate by becoming plasma cells | license APCs = activate CTLs

37
Q

Where are Tfh cells found?

A

mainly in secondary lymphoid organs

38
Q

What are the 2 effector functions of Th1 cells?

A

fights intracellular pathogens (bacteria and virus) | activates macrophages

39
Q

What is the role in disease of Th1 cells?

A

autoimmunity, tissue inflammation

40
Q

What does IFN-gamma do?

A

activates macrophages | turn on ISGs in presence of intracellular pathogen

41
Q

What do IL4 and IL5 do?

A

induce BM to make more granulocytes (eosinophils)

42
Q

What does IL13 do?

A

induces more mucus production in goblet cells

43
Q

What does IL17 do?

A

induces stromal cells to make more cytokines = help increase production of neutrophils

44
Q

What does IL22 do?

A

induces epithelial cells to make more antimicrobial peptides

45
Q

What does IL21 do?

A

helps B-cell become plasma cell and undergo isotype switching

46
Q

What do IL10 and TGF-beta do?

A

suppresses effector function of dendritic cells and T-cells

47
Q

What activates B-cells?

A

when antibody binds to antigen = induce B-cell to undergo clonal expansion

48
Q

What are the 3 ways B-cells can be activated?

A

T-cell dependent antigens (TD) | T-cell independent antigens 1 (TI-1) | T-cell independent antigens 2 (TI-2)

49
Q

What are the 3 signals that are needed for a B-cell to be activated with T-cell dependent antigens?

A

BCR in contact with antigen | CD40/CD40L costimulation with Th cell | cytokine signaling

50
Q

What are the 2 signals that are needed for a B-cell to be activated with T-cell independent antigens 1 (TI-1)?

A

antigen bind directly to BCR | stimulation from PRR (ie: TLR)

51
Q

What is the signal that ia needed for a B-cell to be activated with T-cell independent antigens 2 (TI-2)?

A

(in the case with complement) complement receptor and antibody bound together

52
Q

Where does B-cell activation generally occur?

A

lymph nodes and spleen with T-cells

53
Q

What is the role of lipid rafts in B-cell activation?

A

brings BCRs together

54
Q

What is the role of ITAM regions in B-cell activation?

A

help get full activation of signaling molecules

55
Q

What are the 2 BCR isotypes does IL4 induces? (class-switching)

A

IgG1 | IgE

56
Q

What are the 2 BCR isotypes TGF-beta induces? (class-switching)

A

IgA | IgG2b

57
Q

What is the BCR isotype IL5 induces? (class-switching)

58
Q

What are the 2 BCR isotypes IFN-gamma induces? (class-switching)

A

IgG3 | IgG2a

59
Q

Which B-cells will undergo class-switch recombination?

A

one that has already undergone VDJ recombination but constant regions have not yet recombined

60
Q

Which enzyme initiates class switching recombination process?

A

AID = activation induced deaminase

61
Q

What activates class switch recombination

A

cytokine environment Tfh produces = prompts certain type of class switch recombination = specific antibody produced

62
Q

When does class switch recombination occur? (at what cell process)

A

recombination of constant region occurs at mRNA transcript level

63
Q

Where and when does class switch recombination occur?

A

lymph nodes and spleen after antigen contact

64
Q

What are the 2 polarizing cytokines for Treg?

A

IL2 | TGF-beta

65
Q

What are the 2 effector cytokines for Treg?

A

IL10 | TGF-beta

66
Q

What is the master transcriptional regulator (gene) for Treg?

67
Q

What are the 3 polarizing cytokines for Th17?

A

IL6 | IL23 | TGF-beta

68
Q

What are the 2 effector cytokines for Th17?

A

IL17 | IL22

69
Q

What is the master transcriptional regulator (gene) for Th17?

A

ROR-yt (gamma-t)

70
Q

What is the polarizing cytokine for Th2?

71
Q

What are the 3 effector cytokines for Th2?

A

IL4 | IL5 | IL13

72
Q

What is the master transcriptional regulator (gene) for Th2?

73
Q

What are the 2 polarizing cytokines for Tfh?

A

IL6 | IL21

74
Q

What are the 2 effector cytokines for Tfh?

A

IL4 | IL21

75
Q

What is the master transcriptional regulator (gene) for Tfh?

76
Q

What are the 3 polarizing cytokines for Th1?

A

IL12 | IL18 | IFN-gamma

77
Q

What are the 2 effector cytokines for Th1?

A

IFN-gamma | TNF

78
Q

What is the master transcriptional regulator (gene) for Th1?

Immunology (15 decks)

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