AGET Flashcards
How do Tcells freely move into the lymph nodes?
→through high endothelial venule
What does Tcell recirculation and acativation depend on?
→chemokines
What happens if a Tcell goes to second lymph node without encountering an antigen?
→it goes back to circulation until it finds antigen
What are the secondary lymphoid organs?
→spleen
→lymph nodes
What does activation of naive Tcells in lymph nodes result in?
→development of effector cells
What does activation of effector Tcells at site of infection result in?
→eradication of microbe
What do activated dendritic cells express?
→high levels of MHC2
→CD80/86
What do APCs also secrete?
→co-stimulatory
What activates dendritic cells?
→PAMPs
→cytokines
What factors activate macrophages?
→PAMPs
→Tcell help, IFN-gamma
What do activated macrophages express?
→MHC1
→MHC2
→CD80/86
What do activated B-lymphocytes express?
→MHC1
→MHC2
→CD80/86
What are the three signals required for naïve Tcell activation?
→Antigen recognition through MHC and TCR
→Co-stimulation
→ Cytokines
Where are most co-stimulatory signals found in naïve Tcell activation?
→dendritic cells
→also macrophages or Bcells
What are two co-stimulatory signal molecules needed for Tcell naive activation?
→B7:CD28 interaction
Which cell expresses CD28?
→Tcell
Which cell expresses B7(CD86)?
→APC
→B7-1 (CD80) and B7-2 (CD86)
How is B7 activated in dendritic cells?
→activated by PAMPs
How do Tcells activate APCs?
→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
Give three examples of negative co-stimulatory molecules
→CTLA-4
→PD-1
→LAG-3
What do negative co-stimulatory molecules do?
→inhibit the downstream effector processes initiated by TCR MHC/peptide interaction
Which cells are negative co-stimulatory molecules expressed on?
→naïve Tcells
What types of cells are PD-1 molecules mostly expressed on?
→Tcells in peripheral tissues
→Bcells
→myeloid cells
→inducible
What does CTLA-4 on Tcells bind to?
→CD86(B7-1) on APC
→prevents activation of Bcells
When is CTLA-4 epxressed?
→2-3 days post stimulation
What does CTLA-4 have a high affinity for?
→high affinity/avidity for CD80
What effect does CTLA-4 have on CD28?
→opposing effects because it binds laterally
What does CD28 bind to and what is the effect?
→CD80/86
→co-stimulation
On which cells is CTLA4 mostly expressed on?
→T cells in secondary lymphoid organs
Compare CTLA4 and CD28
→CTLA4 peak levels of expression lower than CD28 but avidity of interaction is much higher
What is ICOS?
→costimulatory molecule expressed mainly on activated CD4+ T-cells following activation
What are the cytokines released by APCs for naive Tcell activation?
→IL-6
→IL-12
→TGF-beta
→IL-4
What are the outcomes of cytokines secreted by APCs for activation?
→activation
→survival
→differentiation
→Tcell polarisation
What can cytokines drive Tcells to differentiate into?
→Th1
→Th2
What cytokines do Th1 cells secrete?
→IFN-gamma
→IL4,5,10
→cell mediated immunity
Which cytokine helps differentiation into Tregs and what is the transcription factor it has?
→TGF-beta
→FoxP3
Which cytokines help differentiation into Tfh cells and what is the transcription factor it has?
→IL-6
→Bcl6
Which cytokines help differentiation into Th17 cells and what is the transcription factor it has?
→Il-2, IFN-gamma
→T-bet
Which cytokines help differentiation into Th2 cells and what is the transcription factor it has?
→IL-4
→GATA3
Which pathogen is TH17 good for?
→bacteria
Which pathogen is Th1 good for?
→viral
→intracellular pathogens s
Which pathogen isTh2 good for?
→parasites
→allergic responses
What type of secretion is IL-2 and IL-12 by Tcells?
→IL-2= autocrine
→IL12= paracrine, released by APC
What is the effect of IL-2?
→growth, survival and differentiation factor for T cells and Tregs
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
What is the receptor for IL-2?
→CD25
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
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
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
What cells do Th1 cells interact with?
→macrophages
What is the effect of Th2 cells?
→release cytokines for eosinophils, mast cells, plasma cells
What cells do Th17 interact with?
→neutrophils
What cells do Tfh cells interact with?
→Bcell via IgM
→results in isotype switching and affinity maturation
Which cells do Tregs interact with
→immature dendritic cells
→results in lack of Tcell activation
What are the master transcription factors of Th1 cells?
→T-bet,
→STAT1 and 4
→IFNgamma can amplify response
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
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
What are the transcription factors of TH2?
→IL-4 activates STAT6 which promotes expression of GATA 3 very important transcription factor
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
What are the functions of Tfh cells?
→IgE production
→mast cell degranulation
