Lecture 9 - T-cell mediated responses I Flashcards
Mounting an appropriate immune response: what is needed and what causes this to happen?
For immunity - an appropriate and adequate pathogen-specific must occur
This is largely achieved by cytokines cause CD4+ T-cell activation which allows for a pathogen-specific response
Naive CD4+ T-cells: what are the types and how do they differ?
Circulatory T-cells are inactivated, once activated they differentiate
Th1 - intracellular pathogens
Th2 - extracellular pathogens
Th17 - Fungal and extracellular bacterial pathogens
Tfh (follicular helper) - promotes b-cell activation
Th9 - anti-parasite, anti-tumour immunity, auto-immunity, and triggering allergic inflammation (may not be an actual subset? ER)
Tregs - control immune responses (prevents extreme immune responses)
T-cell nomenclature: why is it so strange?
Named after the interleukin they produce
What three signals are required for T-cell activation
- T-cell-antigen recognition (MHCII)
- Co-stimulatory molecule binding
- Cytokines
Cytokines: where can they come from?
- Dendritic cells
- Innate lymphoid cells
- Mast cells
- Macrophages
- Epithelial cells
IL-2: what is it and what does it do?
Growth factor for T-cells through STAT5 signalling - acts in an autocrine/paracrine manner for the T-cells themselves - prevents them from dying, promotes CD8+ T-cell activity
STAT: what is it, what does it do, and what are some examples?
Signal transducer of activation
Family of transcription factors that determine the differentiation of T-cells
- STAT1 - along with STAT4 it promotes T-bet expression
- STAT2 - ? (ER)
- STAT3 - promotes RORα/γt expression, promotes Tfh differentiation (differentiated by cytokines promoting the pathway)
- STAT4 - along with STAT1 it promotes T-bet expression
- STAT5 - induces proliferation
- STAT6 - promotes GATA3 expression
Epigenetics: what is it and what is an example?
Any change that modifies gene activity without altering the base DNA sequence
DNA methylation in promoter region or gene regulatory region leads to making gene more or less accessible for transcription
Epigenetics: how may it affect T-cells?
Methylation of DNA may occur causing genes to be ‘locked’ and preventing certain types of differentiation
DNA methylation: what is it, is it heritable, and what is it regulated by?
Methylation of DNA - may result in gene expression being more/less accessible for transcription
Yes, from the mother cell to the daughter cell so any methylation will pass down to populations formed after division
Methylation patterns regulated by DNA methyl transferases
Th1 cells: what pathogens do they detect, how is the differentiation into it achieved, what other cytokines are they affected by, and what is the Th1 specific transcription factor?
Intracellular pathogens - virus, intracellular bacteria, etc
Signal 3 pathways (more specifically the bottom two) result in the stabilisation of T-bet:
* IL-27 and IFN-γ causes STAT1 pathway activation
* IL-12 causing STAT4 pathway activation
IL-2 induces proliferation through the STAT5 pathway
Th1 specific transcription factor - T-bet, cytokines encouraging an immune response - IFN-γ
T-bet: what is it, what does it do, what is it activated by, and what cytokines are produced through its activation?
T-box expressed in T cells - a transcription factor
Promotes differentiation into Th1 cells
- STAT1 pathway through IL-27 and IFN-γ
- STAT4 pathway through IL-12
Th1 cells produce:
- INF-γ (positive feedback)
- IL-2 (positive feedback)
- TNF-α
- TNF-β
Transcription factors: what are they?
Proteins within the body that regulate gene transcription
Th2 cells: what pathogens do they detect, how is the differentiation into it achieved, what other cytokines are they affected by, and what is the Th2 specific transcription factor?
Extracellular pathogens - helminth parasitic worms, etc
Signal 3 pathways result in the stabilisation of GATA3:
* IL-4 induces proliferation via STAT6 signalling
IL-2 induces proliferation through the STAT5 pathway
GATA3
GATA3: what is it, what does it do, what is it activated by, and what molecules are produced through its activation?
Guanine-adenine-thymine-adenine (GATA) binding protein 3
Detect GATA sequences and bind, promoting gene expression - promotes T-cell differentiation into Th2 cells
IL-2 through the STAT5 pathway and IL-4 through STAT6 signalling
- IL-13 - promotes effects that defend against extracellular parasites
- IL-4 along with IL-13 promotes M2-like macrophage differentiation (also positive feedback)
- IL-5 - eosinophil recruitment and activation
- IL-3 and IL-9 - promoting and activating mast cells
IL-13: what is it produced by and what does it do?
Th2 cells
- Promotes effects that defend against extracellular parasites - epithelial cell repair, mucus production, smooth muscle contraction (epithelial cell layer is becoming less hospitable)
- (Along with IL-4) promotes M2-like macrophage differentiation
IFN-γ
Activates macrophages and cytotoxic T-cells
Th1 cell positive feedback
- INF-γ drives regulation of T-bet
- T-bet causes INF-γ and IL-12R production, resulting in an autocrine and paracrine positive feedback loop
Th2 cell positive feedback
- IL-4 causes GATA3 expression
- GATA3 causes IL-4 production
Th cross inhibition: what is it and how does it occur?
- T-bet inhibits GATA3
- GATA3 inhibits T-bet
This occurs through epigenetic markers which prevent expression (ER?)
Th1 vs Th2 helper cells: what do they detect, what is their master transcription factor, and what do they do?
Th1:
* Intracellular pathogens
* T-bet
* Activate cell-mediated immunity (macrophages CD8+ cytotoxic T-cells)
Th2:
* Extracellular pathogens - parasites
* GATA3
* Promotes tissue repair and granulocyte recruitment and activation
