Lecture 16 - Lymphocyte Subsets (CD4+) Flashcards
Helper T cells
1)
2)
3)
1) Distinct lineage of T cells that express CD4
2) Lineage commitment derives from TCR interaction with MHCII
3) Mostly indirectly contribute to immunity
How can CD4+ help macrophages? 1) 2) 3) 4)
1) If macrophage is infected with intracellular pathogen (EG: Mycobacteria, Salmonella)
2) Macrophage presents pathogen antigen on MHCII
3) CD4+ recognises this, binds, releases IFNg
4) Macrophage increases microbicidal action (exact mechanism not known)
How do CD4+ T cells aid CD8+ response?
1)
2)
3)
1) Dendritic cell has both MHCI and MHCII receptors
2) Cognate CD4+ licenses DC with CD40-CD40L, MHCII-TCR interaction
3) This upregulates costimulatory molecules on DC that can stimulate CD8+ when cognate CD8+ binds
Do cognate CD4+ and CD8+ T cells have to bind the same DC at the same time?
No.
CD4+ licenses DC, then CD8+ can bind to it and be activated.
Amount of time between DC contacting antigen and DC displaying antigen on MHC
~12 hours
Interleukin that stimulates T cell proliferation
IL-2
What does IL-2 do?
Stimulates T cell proliferation
What releases IL-2 to stimulate CD8+ proliferation when CD8+ is being activated by a DC?
The CD8+ itself releases IL-2 and self-stimulates
Which Th cells help B cells?
T follicular helper cells (Tfh)
What happens in a germinal centre when an antigen is presented? 1) 2) 3) 4)
1) Tfh express CCR7 on surface, B cells express CXCR5
2) CXCL13 is expressed in the follicle. CCL19 and CCL21 are expressed in the paracortex.
3) When Tfh and B cells are activated, the upregulate both CCR7 and CXCR5 expression, so that they move to the zone between the follicle and paracrotex.
4) In the zone between the paracortex and follicle, Tfh stimulate B cells
IL-21 role
1)
2)
1) Stimulates B cells to isotype switch to IgG1, IgG3
2) Regulates proliferation of mature B and T cells in response to activating stimuli
CXCR5 ligand
CXCL13
CXCL13 receptor
CXCR5
CCR7 ligand
CCL19, CCL21
CCL19, CCL21 receptor
CCR7
IL-12 subunits
p40, p35
What do p40 and p35 make up?
IL-12
What can p40 complex with to form IL-23?
p19
How can IL-23 be formed?
Complex of p40 and p19
Effect of IL-12
Th1 bias
Effect of IL-6, IL-1 or IL-23
Th17 bias
What biases towards Th-1?
IL-12
Factor released by Th1
IFNg
IL-17 role
1)
2)
3)
1) Strongly pro-inflammatory
2) Activates neutrophils
3) Anti extracellular bacteria
What can bias to Th17?
IL-1, IL-6, IL-23
CD25
Alpha subunit of IL-2 receptor
Th2 released factors
IL-4, IL-5, IL-13
What biases to Th2?
IL-4
Factors released by Th17
IL-17, IL-21, IL-22
How were Treg's discovered? 1) 2) 3) 4)
1) Mice without CD25 created
2) Expected to not be able to mount a T cell response
3) Instead suffered great autoimmunity
4) CD25 absence prevented Treg expression, led to unregulated T cell activation
Treg effects on other cells 1) 2) 3) 4)
1) Reduces CD25+ cell proliferation
Releases IL-10 and TGFb, which:
2) Reduce Th1 proliferation, IFNg release
3) Reduce Th2 proliferation, IL-4, IL-5, IL-13 release
4) Reduce CD8+ activity, IFNg release
Surface proteins of Treg
1) CD25
2) FOXP3
Transcription factor in naive T cell that causes Treg differentiation
FoxP3
Transcription factor in naive T cells that responds to IL-6
Bcl6
Transciption factor in naive T cell which responds to IL-6 and TGFb
RORgammaT
Transcription factor in naive T cell which responds IL-12, IFNg
T-bet
Transcription factor in naive T cell which responds to IL-4
GATA3
What does FoxP3 stimulation result in?
Treg differentiation
What does Bcl6 stimulation in naive T cells result in?
Tfh differentiation
What does RORgammaT stimulation result in?
Th17 differentiation
What does T-bet stimulation result in?
Th1 differentiation
What does GATA3 stimulation result in?
Th2 differentiation
Factors expressed by Treg
IL-10, TGFb,
Factors expressed by Tfh
ICOS, IL-21
Factors expressed by Th17
IL-17, IL-6
Factors released by Th1
IL-2, IFNg
NK T cells
1)
2)
3)
1) Semi-invariant
2) CD1d-restricted
3) Recognise only lipid antigens
What does ‘semi-invariant’ mean with respect to T cells?
Limited repertoire of alpha and beta chains
What do NK T cells arise from?
Double positive thymocytes
Factors released by NK T cells
Potent producers of IL-4, IFNg
gamma/delta T cells 1) 2) 3) 4)
1) Semi-invariant
2) Mostly found in epithelium (skin, gut)
3) Produce cytokines
4) Function not known
Evidence that gamma/delta T cells have a function
Conserved in several species, not removed by evolution
What are NK cells?
Innate lymphocytes, without TCR
