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Basic Immunology- Module 1 > T helper cell subsets > Flashcards

T helper cell subsets Flashcards

1
Q

How are the Th subsets defined?

A

by the different combinations of cytokines that they secrete

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2
Q

what is the function of follicular helper T cells?

A

interact with naive B cells through linked recognition of antigen and traffic to B cell follicles where they promote the germinal center responses

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3
Q

What chemokine receptor do Tfh cells express?

A

CXCR5

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4
Q

what does the term antigen experienced mean?

A

has already seen the antigen (probably from dendritic cell)

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5
Q

What cytokines direct the development of Tfh cells?

A

IL-6; IL-21

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6
Q

What transciption factor is important for Tfh cells?

A

Bcl6

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7
Q

why is Bcl6 important for Tfh cells?

A

required for the expression of CXCR5

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8
Q

What is the receptor CXCR5 for?

A

chemokine CXCL13 produced by stromal cells of the B cell follicle

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9
Q

What cytokine do Tfh cells make a lot of?

A

IL-21

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10
Q

What is hte function of IL-21 produced by Tfh cells?

A

supports the proliferation and differentiation of B cells into plasma cells and supports development of Tfh cells

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11
Q

What types of cytokines do Tfh cells produce?

A

all three types- direct type of antibody production

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12
Q

What does IFNy produced by Tfh cause?

A

activate B cells to produce strongly opsonising antibodies- IgG1 and IgG3

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13
Q

What does IL-4 produced by Tfh cause?

A

B cells to differentiate and tomake IgE

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14
Q

What is the function of IL-17 produced by Tfh cells?

A

generating opsonising antibodies against extracellular pathogens in the context of type 3/Th17 responses

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15
Q

What transcription factor does IL-21 induce in B cells and T cells ?

A

STAT3

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16
Q

What is the function of STAT3?

A

supports proliferation and differentiation

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17
Q

What ligand do activated B cells express which stimulates complete differentiation of Tfh cells?

A

ICOSL

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18
Q

What is the function of ICOS signaling?

A

induces Bcl-6 and c-Maf transciption factors

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19
Q

what is the function of Bcl-6 and c-Maf transcription factors?

A

SAP production (required for sustained contact between B and Tfh cells )

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20
Q

What interaction is critical for CD4 help with CD8 cells?

A

CD40:CD40L interaction

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21
Q

What technical advances in the 1980s allowed the progress of cellular immunology?

A

ability to clone T cells and cytokine assays

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22
Q

What are the important cytokines produced by Th1 cells?

A

IL-2 and IFNy

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23
Q

What are the important cytokines produced by Th2 cells?

A

IL-4 and IL-5

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24
Q

What are the effects of Th1 IFNy?

A

IgG2a; macrophage activation; delayed hypersensitivity

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25
Q

what are hte effects of Il-3; Il-4; IL-5 and IL-13 produced by Th2 cells?

A

IgE; mast cells ; eosinophils stimulation

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26
Q

What cytokines produced by Th2 cells inhibit Th1?

A

IL-4 and IL-10

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27
Q

What are clones which produce both type 1 and type 2 cytokines called?

A

Th0 cells

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28
Q

What is the function of Th1 cells?

A

eradicate infections by microbes that can survive or replicate within macrophages

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29
Q

When is Th1 development induced?

A

IFNy and IL-12

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30
Q

What are type 1 interferons?

A

IFNa and IFNb

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31
Q

What are type 2 interferons?

A

IFNy

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32
Q

What do interferons induce in naive T cells?

A

STAT1 expression

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33
Q

What does IL-12 induce in T cells ?

A

STAT4 expression

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34
Q

What does expression of STAT1 and STAT4 cause the expression of?

A

T-bet- STAT1 induces expression then STAT4 further upregulates T-bet expression and completes Th1 programming

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35
Q

what is T-bet known as?

A

master ergulator of Th1 cell differentation

36
Q

What is the function of T-bet?

A

switches on genes for IFNy and inducible componenet of the IL12 receptor- IL-12Rb2 (IL-12Rb1 is expressed on naive T cells)

37
Q

What cytokine is required for Th2 polarisation?

A

IL-4

38
Q

What does IL-4 induce in T cells?

A

STAT6

39
Q

What transciprtion factor does STAT6 induce?

A

GATA3

40
Q

What is the function of GATA3?

A

activates genes that produce IL-4 and IL-13 as well as inducing its own expression, stabilising Th2 differentiation

41
Q

What factors affect polarisation of Th cells?

A

local cytokine environment; genetic background; strenght of TCR signal; dose of antigen; type of APC; route of antigen administration

42
Q

What are the components of IL-12?

A

p35 and p40

43
Q

What are hte components of IL-23?

A

p19 and p40

44
Q

What cytokines induce the production of IL17 cells?

A

TGF-b; IL-6; IL-23

45
Q

What transcription factor do IL-6 and IL-23 induce?

A

STAT3

46
Q

What is the master regulator of Th17 differentiation?

A

RORyt

47
Q

What is RORyt?

A

a nuclear hormone receptor that stabilises the development of Th17 cells

48
Q

What is the source of IL-6 and TGF-b?

A

innate immune cells activated by microbial products

49
Q

How can IL-17 form a positive feedback loop for Th17 differentiation?

A

causes increased IL6 production by innate immune cells

50
Q

What cytokines do Th17 procue?

A

IL-17; IL-21; IL-22; CCL20

51
Q

What is the function of CCL20 produced by Th17?

A

recruitment of dendritic cells

52
Q

what is the function of IL-22?

A

acute-phase reaction

53
Q

What is the funcion of IL-21?

A

cytotoxic differentiation

54
Q

What is the function of IL-17?

A

recruitment of inflammatory cells; induction of inflam mediators

55
Q

Where are Th22 cells mainly found?

A

epithelial barrier organs e.g skin and lung

56
Q

What chemokine receptors are expressed on Th22?

A

CCR4; CCR6; CCR10

57
Q

Where are the chemokines for the receptors CCR4; CCR6 and CCR10 highly expressed?

A

in the skin

58
Q

What cytokine do Th22 cell produce?

A

IL22

59
Q

what cytokines are important in the development of Th22?

A

IL-6 and TGF-beta

60
Q

What receptor is characteristic of Th22?

A

PDGFR

61
Q

What cytokine induces development of Th9 ?

A

TGFb; IL-4 and TSLP

62
Q

What other helper cell are Th9 related to?

A

sisters of Th2- invovled in allergy and atopy

63
Q

What cytokine do Th9 cells produce?

A

IL9

64
Q

Which cytokines drive development of Tregs?

A

IL-2 and TGFb

65
Q

What transcription factor does IL-2 induce?

A

STAT5

66
Q

What determines whether TGFb signalling leads to development of Tregs or Th17?

A

the presence of IL-6

67
Q

What distinguishes Tregs?

A

expression of FoxP3 and cell surface CD25 and CTLA4

68
Q

What cytokines do Tregs produce?

A

TGF-b and IL10

69
Q

What is the function of Th17?

A

extracellular bacteria and fungi, amplifying neutrophilic responses

70
Q

What effect does IL17 have on B cells?

A

promotes class switching to IgG2 and IgG3

71
Q

What effect do IL-17 and IL-22 have on barrier epithelial cells in the GI, resp, urogenital and skin?

A

stimulate to procue antimicrobial peptides that resist microbial invasion

72
Q

What are the 2 main subsets of Tregs?

A

one becomes committed to regulatory function in thymus: natural/thymicall derived T cells; other- induced/peripheral derived- Tregs

73
Q

What effect does TGFb have on devleoping T cells produced by Tregs?

A

suppresses the differentiation and prolfieration of Th1 adn Th2 cells

74
Q

What effect does IFNy produced by Th1 cells have on other T cells?

A

suppresses devlopemnt of Th17 and Th2 cells

75
Q

What effect does IL-4 produced by Th2 cells have on other T cells?

A

suppresses Th1 and Th17

76
Q

Is T cell polarisation permanent?

A

No- evidence of Th17 cells becoming Th1 and producing IFNy

77
Q

What is the function of Fox-P3

A

interferes with teh interaction between AP-1 and NFAT at the IL-2 gene promoter preventing transciprtional activation of the gene and production of IL-2

78
Q

What is the function of IL-10?

A

inhibits the expression of MHC molecules and costimulatory molecules by APCs; and pro-inflam moelcules by APCs

79
Q

What are Tr1 cells?

A

cells which do not express FoxP3 but produce IL-10

80
Q

What is the principlal membrane-bound effector molecule expressed by Th2 cells?

A

CD40L which induces B cell proliferation and isotype switching

81
Q

What is the function of CTLA-4 expressed on Tregs?

A

compete for B7 expressed on APCs preventing adequate co-stimulation of naive T cells; as well as physcially removing B7 molecules from APCs

82
Q

What is the function of expressing CD25 by Tregs?

A

appear to sequester IL-2 from naive T cells which lack CD25 expression until activated

83
Q

What is a major function of iTregs?

A

prevention of infalmmatory immune responses to the commensal microbiota esp. in the intestines

84
Q

What is produced by intestinal dendritic cells which induces Treg differentiation whilst suppressing Th17 development?

A

retinoic acid

85
Q

How were T helper cells discovered?

A

mice without a thymus developed wasting syndrome and died prematurely; lacked small circulating lymphocytes and failed to reject foreign skin transplants

86
Q

What experiment helped discover that T cells were important in the production of antibody?

A

mice without a thymsu and without bone marrow developed a weak antibody resposne whereas mice with both bone marrow and thymus developed a strong Ab response

87
Q

How was it discovered that B cells rather tahn T cells produced antibody

A

the thymus cells and bone marrow cells from different strains of mice along with antigen were put into a mouse, then the spleen cells taken out and either bone marrow cells or thymus cells removed– those without bone marrow had weak Ab resposne and those without thymus still had strong response

Basic Immunology- Module 1 (31 decks)

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