T Cell Activation Flashcards
What is the first signal of T cell activation?
Bind Ag with MHC via TcR
What do accessory molecules strengthen? And what are the accessory molecules?
Accessory molecules strengthen the association of T cells with APC/TC by providing additional linkages
CD4 to class II MHC (dendritic cells, macrophages, B cells etc) CD8 to class I MHC (all nucleated cells)
Do accessory molecules provide an activating signal?
NO, they only help the activation process
What is ‘I ate it’?
What is ‘To call for help’?
I ate it - CD8 to MHC class I - Tc
To call for help - CD4 to MHC class II - Th
Are TcR, Ag and MHC accessory?
No - it is signal 1
What does the crosslinking of membrane molecules do?
Translocation of co-receptors (CD4/8)
Which brings INTRAcellular domains in contact
What happens if a T cell only receives signal 1?
It will switch off = anergy
Antigen binding signal isn’t enough on its own
What type molecules are involved in signal 2?
Co-stimulatory molecules
How do signalling events occur in signal 2?
B7 on APC binds to CD28 on T cell
Ie. Convey a signal from the cell surface via the cytosol into the nucleus to give rise to specific gene transcription
= signal transduction, an amplification process
What are the common intracellular signals?
- Phosphorylation
- Hydrolysis of inositol phosphates
- Alteration of intracellular calcium and protein kinase C (PKC) activities
What does signal 2 involve? And what do these do?
2nd messengers eg Ca2+, IP3
Activation of transcription factors
Gives an increase in the cytokine IL-2 (& others) & receptors for growth
How is signal 2 inhibited?
CTLA-4 is an alternative high affinity ligand for B7
Interaction of B7 (on APC) with CTLA-4 (on ACTIVATED T cells) results in INHIBITION of activation
How are T helper cells activated?
By binding to an antigen
Th + ag —> gene activation
What is encoded <1/2hr after ag recognition?
Transcription factors
What is encoded 1-2hrs after ag recognition?
Cytokines & their receptors regulate growth & differentiation (IL-2, -2R, -3, -6, IFNγ)
What is encoded > 2 days after ag recognition?
Adhesion molecules
Where does superantigen-induced T helper activation bind? And what does this activate?
Outside groove of MHC molecule
Polyclonal activation
What happens during polyclonal activation? Leading to what?
Overproduction of Th cytokines
Systemic toxicity
What is a superantigen?
Massive immune response not specific to any particular epitope
What happens to IL-2 after 2nd signal?
100x increase in IL-2 (transcription and stable mRNA) production and presence of IL-2 receptors (autocrine/paracrine)
What do the 2 subsets of Th depend on?
The cytokines that they secrete
What are the two subsets of Th?
Th1 and Th2
What cytokines are involved in Th1?
IL-2,IFNγ and TNFβ
Classic CMI: Delayed-Type Hypersensitivity, activate Tc
What cytokines are involved in Th2?
IL-4, -5, -6, -10
Help B cell activation
What does the apoptosis of activated Th do?
Eliminates cells producing high levels of cytokines that are no longer needed?
What do patients with Canale-Smith syndrome fail to do?
Tcell apoptosis - a severe life threatening disease
What is the third signal for the generation of Tc?
Interaction of IL-2 (Th) with new IL-2R (IL-2 Receptor)
What is required for the destruction of Target cells by Tc?
Close membrane contact
What do Tc granules contain? And what do they induce?
Perforin (pore-forming protein)
Granzymes (= fragmentins which are proteases)
Induce apoptosis
What activates Fas on target cell?
FasLigand on Tc
