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12 Cards in this Set
- Front
- Back
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2 main ways of getting rid of virus via innate
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- Type I IFN - produced by every virally infected cell
- Tells neighbors there's a virus around - Slow/halt protein production to prevent viral proliferation - NK cells - actively kill infected cells - Develop from lymphoid line - Large lymphocytes with granules |
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NK cells timeframe
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Usually NK cells kill infected cells for ~5 days
- After that T-cells take over... |
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TLR 3, 7, 9
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TLR's that recognize dsRNA, ssRNA, unmethylated DNA, etc.
- These signal from inside the cell! |
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IFN-β induction
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- Viral dsRNA binds TLR3
- TLR3 activates IRF3 -> goes nuclear - IFN-β transcribed, secreted - Autocrine/paracrine method |
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IFN-β response
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- IFN-β binds own, other receptors
- Activate oligoadenylate synthetase - Produces 2'-5' adenosine oligomers - Activates endoribonuclease -> degrades viral DNA! - Activate PKR - phosphorylates eIF2 - Inhibition of protein synthesis - Induces IFN-α via IRF7 - IFN-B binds to receptor -> IRF7 -> induced IFN-α production |
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Interferon producing cells (NIPCs)
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Dendritic-like cells - produce tons of IFN in response to viral infection!
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Interferon effects
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- Halt viral replication in infected cells
- Warn neighbors - Alert immune system - activate NK cells - Release cytokines -> recruits lymphocytes - Overall = make virus more vulnerable |
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NK cells
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- Develop from lymphoid precursor
- No T-cell receptors! - Cell markers = No CD3 production (used for T-cell activation) - CD56+ = If high - less mature - in lymphoid organs - secrete cytokines - If low - more mature - in blood = very cytotoxic! - NKG2d - activating receptor - Viral activity produce ligands that stimulate, activate NK cell - >30 receptors - express many simultaneously |
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NK receptors
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2 main types = Ig-like and lectin-like
- NK's express diverse combos of these |
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NK activation
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- Initial activation and specific activation
- Initial activation = via IFN-α and -B - IL-12 secreted by macrophages? - enhances maturity/cytotoxicity of NK's - Also induces expression of IFN-γ - IFN-γ only made by NK's - anti-viral properties - Increases cytotoxicity, NK functionality - Specific activation = ensures only attacks infected cells - NKG2d receptor senses MHC Class I proteins - present on all body cells - If normal - generates negative signal - nothing happens - If absent/altered - no negative signal - release granule contents -> cause apoptosis of target |
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ITAM and ITIM signalling
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Immunoreceptor Tyrosine-based Activation/Inhibition Motif
- Basically - all activating receptors have conserved structures internally that are modified by viral action - Change surface appearance - induce NK action |
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NK's and macrophages
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- Macrophages first to arrive - sense pathogens
- Release cytokines to recruit neutrophils, NK's - Macrophages secrete IL-12 -> stimulates growth/release of NK cells - Also induces NK production of IFN-γ - Macrophages and NK's work together... |
