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MICR334 module two > T cell subsets > Flashcards

T cell subsets Flashcards

1
Q

why do we need different T cell subsets?

A

Diverse type of pathogens
Different target sites
Different target cells

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2
Q

how are T cell subsets classified?

A

-Cytokines that induce differentiation
- Transcription factors that control gene expression
-Cytokines produced by the cells

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3
Q

what is the role of cytokines produced by T cells?

A

Controls other cells of the immune response

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4
Q

what is the activation signal in a T cell?

A

comes from the T cell receptor

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5
Q

what is the co-stimulatory signal of a T cell?

A

comes from CD28

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6
Q

what is the role of IL-2 on T cells?

A

controls the amount of immune response
- proliferation
- survival
- growth

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7
Q

what are the features of Th-1?

A

-intracellular pathogen activates APC
- APC produces IL-12
- T cell stimulated to produce IFNg

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8
Q

what are the features of Th-2 ?

A

Parasite activates APC
APC produces IL-4
T cell stimulated to produce IL-5

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9
Q

what are the features of TH17?

A

-Pathogen activates APC
- APC stimulates production of IL-23
- T cell stimulated to produce IL-17

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10
Q

what is the role of IFNg in Th-1 cell responses?

A

Stimulates macrophages to increase phagocytosis
stimulates CD8 T cells to kill infected cells
Stimulates B cells to make antibody to enhance phagocytosis

  • acts in intracellular infection
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11
Q

what is the role of IL-4, IL-5 and IL-13 in Th2 immunes responses?

A

stimulates mast cell eosinophils to destroy worms
Stimulates CD4 T cells to produce more IL-4, IL-5, and IL-13
Stimulates B cells to make more antobody to bind pathogens

  • acts in extracellular infection
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12
Q

what is the role of IL-17 in Th17 mediated immune responses?

A

stimulate neutrophils to increase inflammation
stimulates CD4 T cells to produce IL-22
In autoinflammatory diseases it is active (MS and IBD)

  • acts in extracellular infections (fungus)
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13
Q

what are the general molecules that control T cell subset differentiation?

A

Cytokine
Signalling pathway (JAK-STAT)
Transcription factor
Cytokine genes

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14
Q

what are the steps in the JAK STAT signalling cascade?

A
  1. binding of cytokine to receptor = the receptor dimerises
  2. this brings receptor associated JAKs in close
  3. JAKs phosphorylate each other in tyrosine residues
  4. activated JAKs phosphorylate receptor
  5. receptor phosphorylation creates binding sites for STATs
  6. STATs bind, get phosphorylated bu JAKs, then dissociate
  7. STATs dimerise and translocate to the nucleus
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15
Q

what STAT is involved in Th1 cell differentiation?

A

STAT4

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16
Q

what is the transcription factor in T cell differentiation?

A

Tbet

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17
Q

What does IFNg cause?

A

Increased expression of TLRs
Increased MHC expression
Increased chemokine secretion
Increased macrophage activation
Increased phagocytosis

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18
Q

what STAT is involved in Th2 cell differentiation?

A

STAT6

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19
Q

what transcription factor in involved in Th2 cell differentiation?

A

GATA3

20
Q

what is the role of IL-4?

A

Activates B cells
Enhances IgG and IgE production
Suppress proinflammatory mediators (IL-1, TNF)

21
Q

what is the role of IL-4?

A

Stimulates B cells to make IgE

22
Q

what is the role of IL-5?

A

Activates mast cells and basophils

23
Q

what is the role of IL-13?

A

Stimulates mucus production

24
Q

what immune responce is IL-2?

A

response against parasites
-also associated with atopy and allergy

25
Q

what STAT is involved in the differentiation of Th17 cells?

A

STAT3

26
Q

what transcription factor is involved in Th17 differentiation?

A

RORyc

27
Q

why is Th17 differentiation supported by additional receptor mediated stimulation via the JAK STAT pathway?

A

About keeping Th17 cell in their differentiated state as they are very unstable

28
Q

what is the role of IL-17?

A

Promotes recruitment of neutrophils
Activates innate immune cells
Enhances B cell functions
Induces pro-inflammatory cytokines
Can promote production of IL-10 to reduce inflammation

29
Q

what is the role of IL-22?

A

stimulate epithelial cells to produce anti-mocrobial peptides

30
Q

what is the role of IL-23?

A

promotes maintenance of Th17 phenotype

31
Q

what are regulatory T cells?

A
  • Immune responses to pathogens cause damage
  • Need to control the scope and size of the immune response
  • Autoreactive cells escape regulation in development
  • need to control autoimmune responses
32
Q

what are thymic Tregs?

A

Thymic Tregs come from the thymus and are already a Treg

33
Q

what are induced Tregs?

A

Induced Tregs develop from naive T cell in the periphery in response to antogen activation and cytokine signals

34
Q

what is CD25?

A

IL-2R alpha chain that is constitutively expressed on Tregs

Highly expressed on human Tregs

35
Q

how are Tregs defined?

A

By expression of CD25 in conjunction with low expression of CD127

36
Q

what is the transcription factor of Tregs?

A

FOXP3

37
Q

how do Tregs work?

A
  • Repress the transcription of pro-inflammatory genes (IL-2 and IFNg)
  • Enhance the transcription of anti-inflammaotry genes (IL-10, CTLA-4)
38
Q

why can CD25 and FOX3 alone not classifiy a T cell as a Treg cell?

A

Conventional T cell populations can upregulate both of these markers after activation

39
Q

how do you define a Treg?

A

Only Tregs express FOXP3 over their whole life
- Demethylation of FOXP3 locus only occurs in Tregs with stable FOXP3 expression and so is used to classify a Treg.

40
Q

what STAT systems control Treg differentiation?

A

STAT3 and STAT5

41
Q

what is the function of Tregs?

A

-suppress effector T cell function
-Suppress effector T cell activation
- Suppress effector T cell proliferation
- Promote healing

42
Q

what is the function of IL-10?

A

supresson

43
Q

how does IL-10 function?

A

-inhibts antigen presentation by macrophages
-Inhibits pro-inflammatory cytokine production by macrophages
- Enhances production of anti-inflammatory IL-1 receptor antagonist
- Inhibits costimulation signals by macrophages
- Down regulates IFNg and IL-2 production
-Induced anergy
-Stimulates secretory IgA production by B cells

44
Q

what is the role of TGF beta in cytokine mediated supression?

A

-Converts naive T cells into Tregs
- inhibits activation of T cells
- Inhibits activation of macrophages
- heals intestinal epithelial barrier

45
Q

how does CTLA4 act in suppression by cell surface molecules?

A

-Competition for binding to CD80/CD86
- Inhibition of TCR signalling
- Shortening of dwell time between baive T cells nd APCs
- Similar effect of ICOS

46
Q

what is supression by metabolic control?

A

Tregs induce T cell anergy
- reduce glucose signalling (IL-2)
- Produce tryptophan metabolites - inhibit T cell growth

MICR334 module two (6 decks)

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