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MIMM 214 > T Cells 5 > Flashcards

T Cells 5 Flashcards

1
Q

what cytokines are involved in TH17 signal 3?

A
  1. THF-beta
  2. IL-6
  3. IL-23
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2
Q

what are the effector cytokines of TH17?

A
  1. IL-17
  2. IL-22
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3
Q

what is the master transcriptional regulator of TH17?

A

RORgammaT

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4
Q

how did the discovery of TH17 change the study of immunology?

A

originally believed TH1 and TH2 were the only T cells

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5
Q

what are the 2 general roles of TH17 cells?

A
  1. enhance neutrophil response
  2. mucosal immunity
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6
Q

what 2 types of pathogen do TH17 cells respond to?

A
  1. extracellular bacteria
  2. fungi
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7
Q

are TH17 cells involved in pro or anti-inflammatory response?

A

pro-inflammatory

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8
Q

what type of disease are TH17 cells involved in?

A

autoimmune disorders

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9
Q

describe the steps of TH17 activation

A
  1. signal 3: IL-6, IL-23, TGF-beta
  2. TF: STAT3 activated
  3. master transcriptional activator: RORgammaT gene is activated
  4. IL-17 and IL-22 secreted
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10
Q

IL-17 and IL-22 stimulate the secretion of what molecules? (3)

A
  1. Cytokines
  2. Chemokines
  3. Antimicrobial peptides
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11
Q

what type of autoimmune diseases and allergies are TH17 responses involved in? (5)

A
  1. Psoriasis
  2. Inflammatory bowel disease
  3. Asthma
  4. Rheumatoid arthritis
  5. MS
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12
Q

what type of cytokine is IL-17?

A

pro-inflammatory

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13
Q

what is the TH17 response called?

A

Type 3 Response

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14
Q

what are the 5 effector functions of TH17?

A
  1. induce production of antimicrobial peptides
  2. increase epithelial turnover
  3. induce other cells to produce G-CSF
  4. induce other cells to produce chemokines
  5. attract more TH17 cells
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15
Q

how does TH17 induce production of antimicrobial peptides?

A

IL-17 and IL-22 bind receptors and can induce epithelial cells to produce antimicrobial peptides

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16
Q

what do the antimicrobial peptides produced from TH17 do?

A

contributes to killing/slowing replication of bacteria

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17
Q

how does TH17 increase epithelial turnover?

A

IL-22 increases division and shedding of epithelial growth

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18
Q

what is the result of epithelial turnover by TH17? why?

A

Reduced bacterial growth

because bacteria adhere to epithelium to be able to colonize –> if increased turnover, hard for bacteria to grow and colonize

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19
Q

what cells do TH17 cells stimulate to make G-CSF? what cytokines do this?

A

IL-17 acts on stromal and myeloid cells which secrete G-CSF

20
Q

what does secretion of G-CSF do? what type of mechanism is this?

A

enters circulation and targets bone marrow precursors to differentiate into neutrophils

ENDOCRINE

21
Q

what cells do TH17 cells stimulate to make chemokines? what cytokines do this?

A

IL-17 acts on stromal and epithelial cells

22
Q

what are the 2 types of cells that TH17 attracts with chemokines?

A
  1. Neutrophils
  2. additional TH17 cells
23
Q

what do the chemokines secreted due to TH17 lead to?

A
  1. chemokines attract NEUTROPHILS
    neutrophils cause:
    1. phagocytosis
    2. form NETs
    3. cytokines induce the release
    of granules that kill bacteria
    (extracellular in this case)
    and fungi
  2. chemokines recruits additional TH17 cells
24
Q

how do TH17 cells affect macrophages?

A

IL-17 from TH17 will induce macrophages to secrete pro-inflammatory cytokines, like IL-1beta and TNF-alpha –> these will recruit more neutrophils, etc. to site of infection

25
Q

what is psoriasis?

A

autoimmune disease that causes scaly red and white patches on the skin

26
Q

what cytokine is a target for psoriasis treatment?

27
Q

what type of treatment is used for psoriasis?

A

monoclonal antibodies

28
Q

what are monoclonal antibodies?

A

antibodies produced by a single clone of B cells so that they are all identical

they bind specifically to the target to either activate or inhibit its activity

29
Q

what are the 2 approaches to targeting IL-17 in psoriasis?

A
  1. IL-17 receptor antagonist –> blocks signaling from IL-17 receptor
  2. anti-IL-17 neutralizing antibodies –> binds IL-17 and prevents it from interacting with receptor
30
Q

why are ppl taking anti-IL-17 antibody more likely to have extracellular fungus Candida albicans than ppl not taking treatment?

A

TH17 usually targets extracellular fungi so without IL-17 you cannot target the fungus

i.e. TH17 activity reduced –> immunocompromised

31
Q

what is signal 3 of TFH cells?

32
Q

what effector cytokines are produced for TFH cells?

A

IL-21 (main, in high quality)

either type 1 (IFNgamma), type 2 (IL-4), or type 3 (IL-17)

33
Q

what determines whether type 1 (IFNgamma), type 2 (IL-4), or type 3 (IL-17) is produced by TFH?

A

each type produces a specific antibody depending on pathogens

34
Q

what is the master transcriptional regulator of TFH cells?

35
Q

what is the function of TFH cells?

A

activate B cells in lymph node

36
Q

describe the signaling of TFH cells

A
  1. signal 3: IL-6, but exact differentiation requirements not exactly clear
  2. TF: STAT3 activated
  3. master transcriptional regulator: Bcl-6
  4. secretes IL-21, and IFN-gamma/IL-4/IL-17
37
Q

what 2 T cell types use STAT3 as a transcription factor? how is it determined what master transcriptional activator is activated (and eventually the type of T cell)?

A

TH17 and TFH cells use STAT3

STAT3 is activated in both cases.
If TFH is needed, STAT3 is activated then other molecules are released to suppress RORgammaT and activate Bcl-6 (and vice versa)

38
Q

describe the activity of TFH cells?

A
  1. TFH cells recognize pMHCII on B cells and directly interact
  2. IL-21 and INFgamma/IL-4/IL-17 activate B cells to produce specific types of antibodies
39
Q

what type of pathogens are targeted by antibodies made by B cells from TFH cell stimulation

A

all types of pathogens

40
Q

what lineage are NKT cells from?

A

lymphoid lineage

41
Q

what is the exact role of NKT cells?

42
Q

what 2 types of cells are NKT cells similar to?

A

T cells and NK cells

43
Q

what are 4 qualities of NKT cells that are similar to T cells?

A
  1. express TCR
  2. developed in thymus
  3. undergo antigen receptor gene rearrangement
  4. release cytotoxic granules that kills target cells and releases larges quantities of cytokines
44
Q

what are 4 qualities of NKT cells that are similar to NK cells?

A
  1. recognize specific lipid and glycolipid peptides on CD1
  2. less diverse
  3. kill target cells via apoptosis with activating and inhibitory receptors
  4. don’t form memory cells
45
Q

why are NKT cells similar and different to T cells in terms of pathogen recognition?

A

similar: express TCR

different: recognize lipid and glycolipid peptides on CD1 (not peptides on MHC)

46
Q

what are the 2 ways that NKT cells can kill cells? which corresponds to NK cells and T cells?

A

T cells: kill by cytotoxic granules and large quantities of cytokines

NK cells: kill by apoptosis via expressing activating and inhibitory receptors

47
Q

CD1 vs MHC –> similarities and differences

A

very similar structure with similar subunits

CD1 has LIPID antigen-binding groove
MHC has PEPTIDE antigen-binding groove

MIMM 214 (33 decks)

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