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BIOL31371 > Lecture 9 - T-cell mediated responses I > Flashcards

Lecture 9 - T-cell mediated responses I Flashcards

1
Q

Mounting an appropriate immune response

A

For immunity - an appropriate and adequate pathogen-specific must occur

This is largely achieved by cytokines cause CD4+ T-cell activation which allows for a pathogen-specific response

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2
Q

Naive CD4+ T-cells: what are the types?

A

Circulatory T-cells are inactivated, once activated they differentiate

Th1 - intracellular pathogens
Th2 - extracellular pathogens
Th17 - Fungal and extracellular bacterial pathogens
Tfh (follicular helper) - promotes b-cell activation
Th9 - anti-parasite, anti-tumour immunity, auto-immunity, and triggering allergic inflammation
Tregs - control immune responses (prevents extreme immune responses)

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3
Q

T-cell nomenclature: why is it so strange?

A

Named after the interleukin they produce

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4
Q

What three signals are required for T-cell activation

A
  • T-cell-antigen recognition (MHCII)
  • Co-stimmulatory molecule
  • Cytokines
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5
Q

Where can cytokines come from

A
  • Dendritic cells
  • Innate lymphoid cells
  • Mast cells
  • Macrophages
  • Epithelial cells
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6
Q

IL-2

A

Growth factor for T-cells - acts in an autocrine/paracrine manner for the T-cells themselves

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7
Q

STAT: what is it, what does it do

A

Signal transducer of activation

Family of transcription factors that determine the differentiation of T-cells

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8
Q

Epigenetics: what is it and what is an example?

A

Any change that modifies gene activity without altering the base DNA sequence

DNA methylation in promoter region or gene regulatory region leads to making gene more or less accessible for transcription

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9
Q

Epigenetics: how may it affect T-cells?

A

Methylation of DNA may occur causing genes to be ‘locked’ and preventing certain types of differentiation

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10
Q

DNA methylation: what is it, is it heritable, and what is it regulated by?

A

Methylation of DNA - may result in repressed gene expression

Heritable

Methylation patterns regulated by DNA methyl transferases

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11
Q

Th1 cells: what pathogens do they detect, how is the differentiation into it achieved, and what is the Th1 specific transcription factor?

A

Intracellular pathogens - virus, intracellular bacteria, etc

Signal 3 pathways (more specifically the bottom two) result in the stabilisation of T-bet:
* IL-2 induces proliferation through the STAT5 pathway
* IL-27 and IFN-γ causes STAT1 pathway activation
* IL-12 causing STAT4 pathway activation

Th1 specific transcription factor - T-bet, cytokines encouraging an immune response - IFN-γ

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12
Q

T-bet: what is it, what does it do, what is it activated by, and what molecules are produced through its activation?

A

T-box expressed in T cells - a transcription factor

Promotes differentiation into Th1 cells

  • STAT5 pathway through IL-2
  • STAT1 pathway through IL-27 and IFN-γ
  • STAT4 pathway through IL-12
  • INF-γ (positive feedback?)
  • IL-2 (positive feedback?)
  • TNF-α
  • TNF-β
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13
Q

Transcription factors: what are they?

A

Proteins within the body that regulate gene transcription

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14
Q

Th2 cells: what pathogens do they detect, how is the differentiation into it achieved, and what is the Th2 specific transcription factor?

A

Extracellular pathogens - helminth parasitic worms, etc

Signal 3 pathways result in the stabilisation of GATA3:
* IL-2 induces proliferation through the STAT5 pathway
* IL-4 induces proliferation via STAT6 signalling

GATA3

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15
Q

GATA3: what is it, what does it do, what is it activated by, and what molecules are produced through its activation?

A

Guanine-adenine-thymine-adenine (GATA) binding protein 3

Detect GATA sequences and bind, promoting gene expression - promotes T-cell differentiation into Th2 cells

IL-2 through the STAT5 pathway and IL-4 through STAT6 signalling

  • IL-13 - promotes effects that defend against extracellular parasites
  • IL-4 along with IL-13 promotes M2-like macrophage differentiation (also positive feedback)
  • IL-5 - eosinophil recruitment and activation
  • IL-3 and IL-9 - promoting and activating mast cells
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16
Q

IFN-γ

A

Activates macrophages and cytotoxic T-cells

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17
Q

Th1 cell positive feedback

A
  • INF-γ drives regulation of T-bet
  • T-bet causes INF-γ and IL-12R production, resulting in an autocrine and paracrine positive feedback loop
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18
Q

Th2 cell positive feedback

A
  • IL-4 causes GATA3 expression
  • GATA3 causes IL-4 production
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19
Q

Th cross inhibition

A
  • T-bet inhibits GATA3
  • GATA3 inhibits T-bet

This occurs through epigenetic markers which prevent expression

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20
Q

Th1 vs Th2 helper cells: what do they detect, what is their master transcription factor, and what do they do?

A

Th1:
* Intracellular pathogens
* T-bet
* Activate cell-mediated immunity (macrophages CD8+ cytotoxic T-cells)

Th2:
* Extracellular pathogens - parasites
* GATA3
* Promotes tissue repair and granulocyte recruitment and activation

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21
Q

Th17 cells: what pathogens do they detect, how is the differentiation into it achieved, are there any cytokines that inhibit them, and what are the Th2 specific transcription factors?

A

Deal with fungal and extracellular bacterial pathogens (also associated with several autoimmune diseases)

Signal 3:
* STAT3 signalling through IL-6
* Smad signalling through TGF-β
* IL-1β
* IL-21
* IL-23

IL-2

RORα and ROR-γT

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22
Q

Positive feedback loops of Th17 cells

A

Not present like within Th1 and Th2 cells

Instead, Th17 relies on accessory cells releasing the cytokines:
* IL-1β
* IL-21
* IL-23

23
Q

RORα and ROR-γT: what are they, what do they do, what are they activated by, and what molecules are produced through their activation?

A

Retinoic acid receptor (RAR)-related orphan receptor α and RAR-related orphan receptorγt

Cause Th17 cell differentiation, results in recruitment of neutrophils (IL17 results in CXCL2 receptor expression) and also result in anti-microbial protein induction

  • STAT3 signalling through IL-6
  • Smad signalling through TGF-β

IL-17A
IL-17F
IL-21

24
Q

Monogenic disorders: what are they, what is an example, what mutations occur in this example, and what is the result of the example?

A

Diseases caused by a single mutated gene

Job syndrome

STAT3 mutations

Results in Th17 deficiency

25
Q

Tfh: what are they, what does it needs for its activation, what types are there, and what do they do?

A

Follilular T helper cells

Signal 3:
* IL-6 via STAT3 signalling
* IL-21 via STAT3 signalling

Different dependent on immune response required: Tfh1, Tfh2, Th17, etc

  • Promotes Bcl-6 expression - inhibits BLIMP-1
  • Expresses CXCR5 - chemokine allowing T-cells to move to B-cells
  • Produces IL-21 key cells in promoting B-cells germinal response
26
Q

Tfh1 cells: what are they, what do they produce, and what is their master transcription factor?

A

Tfh cells with similar phenotypes to Th1 cells - act to support the Th1 response to intracellular infections

  • IFN-γ
  • IL-21
  • IgG2a
  • IgG2c

T-bet

viral infections

27
Q

Tfh2 cells: what are they, what do they produce, and what is their master transcription factor?

A

Tfh cells with similar phenotypes to Th2 cells - act to support the Th2 response to extracellular parasites

  • IL-21
  • IL-4
  • IL-13
  • IgE

GATA3

IgE - mast cells, large pathogens in GI tract

28
Q

Tfh17 cells: what are they, what do they produce, and what is their master transcription factor?

A

Tfh cells with similar phenotypes to Th17 cells - act to support the Th17 response to extracellular parasites

  • IL-17
  • IL-21
  • IgG2a
  • IgG3

ROR-gammaT

IgG2a
IgG3

29
Q

Tfr cells: what are they, what do they do, what is their master transcription factor: and what do they produce?

A

T follicular regulatory cells

Inhibit immune activation - regulation

Foxp3

CTLA-4

30
Q

Foxp3: what are they, what do they do, what are they activated by, and what molecules are produced through their activation?

A

Forkhead box P3 protein

Regulate immune responses

?

CTLA-4

31
Q

IL-1β: what does it do and what Th cells is it associated with?

A

Promotes Th17 differentiation and expansion

Th17 cells

32
Q

IL-2: what does it do and what Th cells is it associated with?

A

Causes STAT5 pathway activation - proliferation and survival of T-cells

Th1 and Th2 cells

33
Q

IL-3: what does it do and what Th cells is it associated with?

A

Promotes mast cell

Th2 cells

34
Q

IL-4: what does it do and what Th cells is it associated with?

A

Promotes differentiation into Th2 cells via the STAT6 pathway - stabilising GATA3

Promotes M2-like macrophage differentiation along with IL-13 and promotes tissue repair

Th2 cells, Tfh2 cells

35
Q

IL-5: what does it do and what Th cells is it associated with?

A

Eosinophil recruitment and activation

Th2 cells

36
Q

IL-6: what does it do and what Th cells is it associated with?

A

Activates the STAT3 signalling pathway, results in activation of ROR-αand RORγt TFs

Th17 cells, Tfh cells

37
Q

IL-9: what does it do and what Th cells is it associated with?

A

Promotes mast cell

Th2 cells

38
Q

IL-12: what does it do and what Th cells is it associated with?

A

Encourages Th1 differentiation through the STAT4 pathway - stabilising T-bet

Th1 cells

39
Q

IL-13: what does it do and what Th cells is it associated with?

A

Promotes epithelial cell repair, mucus production, and smooth muscle contracting

Th2 cells, Tfh2 cells

40
Q

IL-17: what does it do and what Th cells is it associated with?

A

Results in recruitment of neutrophils through CXCL2 receptor expression, the main neutrophil recruitment factor and also induce anti-microbial gene expression

IL17A - ?
IL17F - ?

Th17 cells

41
Q

IL-21: what does it do and what Th cells is it associated with?

A
  • Promotes Th17 differentiation and expansion
  • Activates the STAT3 pathway, activating Tfh cells

Th17 cells and Tfh1/2/17 cells

42
Q

IL-23: what does it do and what Th cells is it associated with?

A

Promotes Th17 differentiation and expansion

Th17 cells

43
Q

IL-27: what does it do and what Th cells is it associated with?

A

Causes STAT1 pathway activation along with IFN-γ - differentiation into Th1 cells stabilising T-bet

Th27 cells

44
Q

IFN-γ: what does it do and what Th cells is it associated with?

A

Causes STAT1 pathway activation along with IL-27 - differentiation into Th1 cells by stabilising T-bet

Th1 cells, Tfh1 cells

45
Q

TGF-β: what does it do and what Th cells is it associated with?

A

Causes Smad signalling pathway activation, resulting in activation of ROR-αand RORγt TFs

Th17 cells

46
Q

Bcl-6: what does it do and what Th cells is it associated with?

A

Key transcription factor associated with being a Tfh cell, inhibits BLIMP-1 expression

Tfh cells

47
Q

CXCR5: what does it do and what Th cells is it associated with?

A

Chemokine allowing T-cells to move to B-cells

Tfh cells

48
Q

IgG2a: what does it do and what Th cells is it associated with?

A

Antibody that is used to clear viral infections

Tfh1 cells

49
Q

IgG2c: what does it do and what Th cells is it associated with?

A

Antibody that is used to clear viral infections

Tfh1 cells

50
Q

IgG3: what does it do and what Th cells is it associated with?

A

?

Tfh17 cells

51
Q

IgE: what does it do and what Th cells is it associated with?

A

Antibody that results in mast cell activation and clearing of pathogens in the GI tract

Tfh2 cells

52
Q

CTLA-4: what does it do and what Th cells is it associated with?

A

Cytotoxic T-lymphocyte antigen 4 - key Treg cytokine

Tfr cells

53
Q
A

BIOL31371 (17 decks)

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