Lecture 16 - Lymphocyte Subsets - CD4+ T cells Flashcards
What are the functions of ‘helper’ T cells?
Indirect elimination of pathogens
Through assistance to other cells w/ cytokine release
Help for:
• B cells
• CTLs (though DCs)
• Macrophages
Describe the restriction of helper T cells
MHC class II restricted
How are Th cells activated?
Dendritic cell presentation of antigen in the context of MHC class II
Can CD4+ T cells be converted into a CD8+ T cell?
No
But CD4+ can differentiate into different lineages
What determines commitment of CD4+ T cells?
- TCR interaction w/ MHC II (Signal I)
* APC cytokine release (Signal III)
Describe T cell help for macrophages
- Infected macrophages are expressing:
• MHC II + antigen
• CD40
• IFN-γ receptor - Th1 cells recognise the foreign antigen in the context of MHC class II w/ TCR
- Th1 releases IFN-γ which binds to IFN-γ receptor on macrophage
- IFN-γ assists in eliminating intracellular pathogens:
• increased ROS etc.
Which pathogens cause intracellular infections of macrophages?
Mycobacteria → Tuberculosis
Salmonella → Typhoid fever
What is the definition of AIDS?
CD4+ T cell blood concentration less than 200 per mL
Describe T cell help for CTLs
Helper T cells help the DCs to help the CTLs
(ménage à trois)
- Upregulation of CD40L on the CD4+ T cell
- (Newly acquired) CD40L on CD4+ T cell stimulates CD40 on DC
- DC up-regulation of co-stimulatory molecules, such that it’s able to provide the signals to CD8+ T cells
- B cell production of IL-2 also stimulated by DCs, released onto IL-2R on T cell
Describe the role of IL-2 in activation of CD8+ T cells
CD8+ T cells release IL-2 onto themselves
(Autocrine signalling)
This is the signal for proliferation of T cells
Which type of ‘helper’ T cells assist B cells?
Describe this ‘help’
Tfh cell (follicular helper cell)
- TFH upregulate CXCR5 and B cells upregulate CCR7 → they meet in the middle at the MZ
- Cognate interactions between an antigen-specific TFH and activated B cells
- CD40L ligates CD40 on the B cell
- Upregulation of ICOSL and IL-21R on B cell
- ICOSL interacts with ICOS on the TFH resulting in IL-21 production
- IL-21 binds to IL-21R on the B cell, upregulating Bcl6
- Bcl-6 is s transcription factor needed to ensure survival of the activated B cells ensuring continued germinal centre reactions
Where is CXCL13 primarily expressed?
In the follicle
What is the ligand for CCR7?
Where are these expressed?
CCL19 & CCL21
In the paracortex
How do we get Th cells to move to the periphery of the follicle?
Upregulation of:
• CXCR5
as well as previous expression of
• CCR7
Follows two chemokine gradients, towards:
• Follicle
• Paracortex
So it is stuck in the middle, which is the boundary between the paracortex and the follicle
Describe the outcome if identical CD4+ T cells are stimulated with: • IL-4 • IL-12 • IL-6 • IL-6 + TGF-β • TGF-β
IL-4 • differentiates into Th2 • Th2 makes IL-4 • Extracellular, anti-parasite immunity • 'Helps' B cells make IgE
IL-12
• differentiates into Th1
• Th1 makes IFN-γ
• Intracellular, viral infections
IL-6
• Differentiates into Tfh cells
• Tfh cells express IL-21 and ICOS
• help B cells at the boundary of the follicle
IL-6 + TGF-β • Differentiates into Th17 • Th17 makes IL-17 • Pro-inflammatory • Extracellular bacterial infection
TGF-β
• Differentiates into Treg cells
• Treg makes IL-10 and TGF-β
What is the role of IL-2 in Th cells?
Autocrine signalling
Required as a growth hormone for proliferation
Is it possible for a Th2 to revert to a Th1?
Yes
Through signalling with IL-12
However, they are committed to being CD4+ cell (can’t become CD8+ T cells)
What is the structure of IL-12?
It is a heterodimer:
• IL-12p40
• IL-12p35
What is the structure of IL-23?
Heterodimer:
• IL-12p40
• IL-12p19