Lecture 11 Flashcards
What activates naive T cells?
Naïve cell activated by peptide presentation by DC on MHC molecule
Where are T cells activated? What 3 Signals do they require to be activated?
Activated in lymph nodes and require 3 signals
Ag recognition, Costimulation, and Cytokines
List the 5 steps involved in the activation of T cells.
1) TCR recognizing and binds to MHC complex in the DC
2) CD4/CD8 complex containing LCK phosphorylates ITAMs on Zeta chains
3) ZAP-70 binds to p-ITAMs and LCK activates ZAP-70 via phosphorylation
4) ZAP-70 phosphorylates LAT and SLP-76, which acts as scaffolding for proteins
5) Activates the MAPK, Ras, and PKC pathways
What are the 3 functions of superantigens?
Activates CD4 T cells without the presence of Ag or other stimulatory factors
Bind MHC2 on APC and variable beta subunit of the TCR; NOT the peptide binding groove
Causes massive proliferation and production of proinflammatory cytokines
Unactivated DCs express low levels of what? While activated express high levels of what?
CD80/86
What are the 3 steps of costimulation (second signal of T cell activation)
- CD28 on naïve cells will bind to the CD80/86 on the DC
- Activation of the pathways that lead to survival factors (Bcl-2), proliferation factors (IL-2), and differentiation factors
- Upregulation of CTLA-4 and other CD28 like receptors
- These will compete with the CD80-86 to help regulate the level and amount of T cell activation towards the end of an infection
How is CTLA4 a CD28 like a regulator for T cells?
CTLA4 is homologous to CD28
Amount of expressed CTLA-4 is correlated with the strength of the activating stimulus
Serves as a measure for when the infection is becoming under control
Will bind to the CD80/86 on activated cells to prevent the further activation of T cells when the infection is beginning to decline
How does PD-1 regulate T-cell responses?
Major function is in the programmed cell death of the T cells following an immune response
Tissues, Macrophage activating factors, B-cells, will express PD1 ligand to bind to the PD1 receptors on the activated T cell
Upon binding, will cause the downregulation of T cell activity, therefore limiting the amount of unnecessary collateral damage
How will the following cytokines determine the differentiation of CD4+ T cells? (Provide the transcription factor it influences and then the final T cell it differentiates into)
IL-12
IL-4
IL-6
TGF-beta
IL-12 –> T-Bet –> Th1
IL-4 –> GATA3 –> Th2
IL-6 –> ROR gamma-t –> Th17
TGF- Beta –> FOXP3 –> Treg
What are the 7 changes in protein expression after CD4+ differentiation?
- Recognition of the TCR to its antigen
- Upregulation of the c-Fos transcription product
- IL-2 production and release
- CD69 expression
- IL-2Ralpha expression
- CD40L expression
- Cell division
What are the 4 functions of IL-2 on CD4+ T cells?
IL-2 is produced as an autocrine signal for T cell growth (both CD4 and CD8)
Increases CD8 and NK cytotoxicity
Stimulates T cells to produce IL-4, IL-5, IFN-gamma
**Promotes the survival of T cells (via Bcl2)
Promotes production of T regulatory cells
IL-2 is the most crucial survival mechanism for T reg: cannot function w/o it
Upon CD4+ T cell activation, how does CD69 expression change?
CD69 expression: decreases the expression of S1PR1 (binds to S1P)
As a result, the activated T cells are unable to leave the LN until they are more mature and differentiated
Upon CD4+ T cell activation, how does CD25 expression change?
AKA IL-2Ralpha component
Takes IL-2 receptor from low affinity to very high affinity
Upon CD4+ T cell activation, how does CD40L expression change?
Helps to stimulate the upregulation of CD80/86 on APC to activate more T cells
List the 3 changes that occur due to the resolution of T cell responses.
- As the infection is resolved, there is a decrease in amount of IL-2
- Lack of IL-2 leads to decrease in Bcl-2 (survival protein) intrinsic apoptosis - Inhibitory receptors PD-1 and CTLA4 lead to cell death
- T reg cells can regulate the survival of the remaining T cells
