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
When is CTLA-4 epxressed?
→2-3 days post stimulation
26
What does CTLA-4 have a high affinity for?
→high affinity/avidity for CD80
27
What effect does CTLA-4 have on CD28?
→opposing effects because it binds laterally
28
What does CD28 bind to and what is the effect?
→CD80/86 | →co-stimulation
29
On which cells is CTLA4 mostly expressed on?
→T cells in secondary lymphoid organs
30
Compare CTLA4 and CD28
→CTLA4 peak levels of expression lower than CD28 but avidity of interaction is much higher
31
What is ICOS?
→costimulatory molecule expressed mainly on activated CD4+ T-cells following activation
32
What are the cytokines released by APCs for naive Tcell activation?
→IL-6 →IL-12 →TGF-beta →IL-4
33
What are the outcomes of cytokines secreted by APCs for activation?
→activation →survival →differentiation →Tcell polarisation
34
What can cytokines drive Tcells to differentiate into?
→Th1 | →Th2
35
What cytokines do Th1 cells secrete?
→IFN-gamma →IL4,5,10 →cell mediated immunity
36
Which cytokine helps differentiation into Tregs and what is the transcription factor it has?
→TGF-beta →FoxP3
37
Which cytokines help differentiation into Tfh cells and what is the transcription factor it has?
→IL-6 →Bcl6
38
Which cytokines help differentiation into Th17 cells and what is the transcription factor it has?
→Il-2, IFN-gamma →T-bet
39
Which cytokines help differentiation into Th2 cells and what is the transcription factor it has?
→IL-4 →GATA3
40
Which pathogen is TH17 good for?
→bacteria
41
Which pathogen is Th1 good for?
→viral | →intracellular pathogens s
42
Which pathogen isTh2 good for?
→parasites | →allergic responses
43
What type of secretion is IL-2 and IL-12 by Tcells?
→IL-2= autocrine →IL12= paracrine, released by APC
44
What is the effect of IL-2?
→growth, survival and differentiation factor for T cells and Tregs
45
What do Tregs cells in the thymus do with IL-2?
→have high levels of receptors for IL2 so they gather IL2 up blocking proliferation
46
What is the receptor for IL-2?
→CD25
47
Describe the different surface molecules during immune response on Tcells
→naive Tcells=TCR →in lymph node= CD69 →proliferation= CD25, IL-2 receptor →activation of DCs, macrophages, Bcells= CD40L →control of response= CTLA-4
48
What happens post TCR signalling?
→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
What determines the cytokines produced by APC for Tcell differentiation?
→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
What cells do Th1 cells interact with?
→macrophages
51
What is the effect of Th2 cells?
→release cytokines for eosinophils, mast cells, plasma cells
52
What cells do Th17 interact with?
→neutrophils
53
What cells do Tfh cells interact with?
→Bcell via IgM | →results in isotype switching and affinity maturation
54
Which cells do Tregs interact with
→immature dendritic cells | →results in lack of Tcell activation
55
What are the master transcription factors of Th1 cells?
→T-bet, →STAT1 and 4 →IFNgamma can amplify response
56
What are the functions of TH1 cells?
→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
What cells do not produce IL-4 and as a result does not contribute to TH2 differentiation?
→Dendritic cells →Eosinophils, basophils and mast cells produce IL-4
58
What are the transcription factors of TH2?
→IL-4 activates STAT6 which promotes expression of GATA 3 very important transcription factor
59
What are the functions of TH2 cells?
→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
What are the functions of Tfh cells?
→IgE production | →mast cell degranulation