AGET Flashcards

1
Q

How do Tcells freely move into the lymph nodes?

A

→through high endothelial venule

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2
Q

What does Tcell recirculation and acativation depend on?

A

→chemokines

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3
Q

What happens if a Tcell goes to second lymph node without encountering an antigen?

A

→it goes back to circulation until it finds antigen

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4
Q

What are the secondary lymphoid organs?

A

→spleen

→lymph nodes

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5
Q

What does activation of naive Tcells in lymph nodes result in?

A

→development of effector cells

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6
Q

What does activation of effector Tcells at site of infection result in?

A

→eradication of microbe

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7
Q

What do activated dendritic cells express?

A

→high levels of MHC2

→CD80/86

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8
Q

What do APCs also secrete?

A

→co-stimulatory

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9
Q

What activates dendritic cells?

A

→PAMPs

→cytokines

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10
Q

What factors activate macrophages?

A

→PAMPs

→Tcell help, IFN-gamma

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11
Q

What do activated macrophages express?

A

→MHC1
→MHC2
→CD80/86

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12
Q

What do activated B-lymphocytes express?

A

→MHC1
→MHC2
→CD80/86

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13
Q

What are the three signals required for naïve Tcell activation?

A

→Antigen recognition through MHC and TCR
→Co-stimulation
→ Cytokines

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14
Q

Where are most co-stimulatory signals found in naïve Tcell activation?

A

→dendritic cells

→also macrophages or Bcells

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15
Q

What are two co-stimulatory signal molecules needed for Tcell naive activation?

A

→B7:CD28 interaction

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16
Q

Which cell expresses CD28?

A

→Tcell

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17
Q

Which cell expresses B7(CD86)?

A

→APC

→B7-1 (CD80) and B7-2 (CD86)

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18
Q

How is B7 activated in dendritic cells?

A

→activated by PAMPs

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19
Q

How do Tcells activate APCs?

A

→via CD40(on dendritic cells) – CD40L interaction

→T cells upregulate CD40L, which binds to CD40 on DCs and stimulates the production of co-stimulatory molecules and cytokines by the DCs

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20
Q

Give three examples of negative co-stimulatory molecules

A

→CTLA-4
→PD-1
→LAG-3

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21
Q

What do negative co-stimulatory molecules do?

A

→inhibit the downstream effector processes initiated by TCR MHC/peptide interaction

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22
Q

Which cells are negative co-stimulatory molecules expressed on?

A

→naïve Tcells

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23
Q

What types of cells are PD-1 molecules mostly expressed on?

A

→Tcells in peripheral tissues
→Bcells
→myeloid cells
→inducible

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24
Q

What does CTLA-4 on Tcells bind to?

A

→CD86(B7-1) on APC

→prevents activation of Bcells

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25
Q

When is CTLA-4 epxressed?

A

→2-3 days post stimulation

26
Q

What does CTLA-4 have a high affinity for?

A

→high affinity/avidity for CD80

27
Q

What effect does CTLA-4 have on CD28?

A

→opposing effects because it binds laterally

28
Q

What does CD28 bind to and what is the effect?

A

→CD80/86

→co-stimulation

29
Q

On which cells is CTLA4 mostly expressed on?

A

→T cells in secondary lymphoid organs

30
Q

Compare CTLA4 and CD28

A

→CTLA4 peak levels of expression lower than CD28 but avidity of interaction is much higher

31
Q

What is ICOS?

A

→costimulatory molecule expressed mainly on activated CD4+ T-cells following activation

32
Q

What are the cytokines released by APCs for naive Tcell activation?

A

→IL-6
→IL-12
→TGF-beta
→IL-4

33
Q

What are the outcomes of cytokines secreted by APCs for activation?

A

→activation
→survival
→differentiation
→Tcell polarisation

34
Q

What can cytokines drive Tcells to differentiate into?

A

→Th1

→Th2

35
Q

What cytokines do Th1 cells secrete?

A

→IFN-gamma
→IL4,5,10

→cell mediated immunity

36
Q

Which cytokine helps differentiation into Tregs and what is the transcription factor it has?

A

→TGF-beta

→FoxP3

37
Q

Which cytokines help differentiation into Tfh cells and what is the transcription factor it has?

A

→IL-6

→Bcl6

38
Q

Which cytokines help differentiation into Th17 cells and what is the transcription factor it has?

A

→Il-2, IFN-gamma

→T-bet

39
Q

Which cytokines help differentiation into Th2 cells and what is the transcription factor it has?

A

→IL-4

→GATA3

40
Q

Which pathogen is TH17 good for?

A

→bacteria

41
Q

Which pathogen is Th1 good for?

A

→viral

→intracellular pathogens s

42
Q

Which pathogen isTh2 good for?

A

→parasites

→allergic responses

43
Q

What type of secretion is IL-2 and IL-12 by Tcells?

A

→IL-2= autocrine

→IL12= paracrine, released by APC

44
Q

What is the effect of IL-2?

A

→growth, survival and differentiation factor for T cells and Tregs

45
Q

What do Tregs cells in the thymus do with IL-2?

A

→have high levels of receptors for IL2 so they gather IL2 up blocking proliferation

46
Q

What is the receptor for IL-2?

A

→CD25

47
Q

Describe the different surface molecules during immune response on Tcells

A

→naive Tcells=TCR

→in lymph node= CD69

→proliferation= CD25, IL-2 receptor

→activation of DCs, macrophages, Bcells= CD40L

→control of response= CTLA-4

48
Q

What happens post TCR signalling?

A

→Modify the expression of surface molecules

→Upregulate cytokine production

→Undergo active rounds of proliferation
→Upregulate expression of pro-survival genes
→Upregulate expression of IL-2 and IL-2R-a

→Differentiate into effector or
memory cells

49
Q

What determines the cytokines produced by APC for Tcell differentiation?

A

→cellular origin of the APC

→maturation and activation status of the APC

→Which pathogens or inflammatory mediators were encountered by the APC

→ tissue environment the encounter takes place

50
Q

What cells do Th1 cells interact with?

A

→macrophages

51
Q

What is the effect of Th2 cells?

A

→release cytokines for eosinophils, mast cells, plasma cells

52
Q

What cells do Th17 interact with?

A

→neutrophils

53
Q

What cells do Tfh cells interact with?

A

→Bcell via IgM

→results in isotype switching and affinity maturation

54
Q

Which cells do Tregs interact with

A

→immature dendritic cells

→results in lack of Tcell activation

55
Q

What are the master transcription factors of Th1 cells?

A

→T-bet,
→STAT1 and 4

→IFNgamma can amplify response

56
Q

What are the functions of TH1 cells?

A

→Induce antibody class switching to IgG (opsonization)

→produces IFN-gamma which produces oxygen and nitrogen species

→IFNg- Help to activate macrophages to ingest and destroy microbes

57
Q

What cells do not produce IL-4 and as a result does not contribute to TH2 differentiation?

A

→Dendritic cells

→Eosinophils, basophils and mast cells produce IL-4

58
Q

What are the transcription factors of TH2?

A

→IL-4 activates STAT6 which promotes expression of GATA 3 very important transcription factor

59
Q

What are the functions of TH2 cells?

A

→eliminate extracellular parasitic infections
→ Promote class switching to IgE, which causes inflammatory cytokines to be released by eosinophils and mast cells
→increase intestinal movement and mucus production
→IgE mediates allergy

60
Q

What are the functions of Tfh cells?

A

→IgE production

→mast cell degranulation