FN - Bacterial Immunity II Flashcards
(12 cards)
What is cell-autonomous innate immunity? (3)
- A defence mechanism used by most animal cells (not just immune cells)
- Relies on viral sensors and interferon responses
- Many components trace back to prokaryotic anti-phage defence systems e.g. :
- cGAS–STING pathway, related to CBASS in bacteria
- TIR domain-containing receptors
- Viperin antiviral proteins
- Gasdermin proteins
What are the three main roles of interferon in response to viral infection?
- Signals uninfected neighboring cells to destroy RNA and reduce protein synthesis → creates an antiviral state
- Signals infected neighboring cells to undergo apoptosis → limits viral spread
- Activates immune cells to enhance the overall immune response
What is the CBASS system and how does it work? (4)
- A bacterial defence system that detects phage DNA
- Activates a cyclase, producing cyclic nucleotides (e.g. cGAMP)
- These nucleotides activate effectors that trigger cell death (abortive infection)
- Effectors degrade membrane, DNA, or other targets to prevent phage replication
What are key features of CBASS systems? (4)
- 4 major types, multiple effector subtypes
- Causes cell death through various mechanisms (e.g., membrane rupture, DNA cleavage)
- Widely distributed and rapidly gained/lost across microbial genomes
- Supports the pan-immunity model in prokaryotes
how does CBASS defence system protect bacteria from phages? (5)
Mechanism:
- Phage infection activates a cyclase
- Cyclase produces cyclic nucleotide signals
- Signals activate effectors that induce cell death (via membrane damage, DNA degradation, etc.)
- This abortive infection sacrifices the host cell to prevent phage spread
- Different CBASS types use distinct effectors (e.g., E1/E2/JAB, TRIP13/HORMA, QueC/TGT/OGG)
How do the CBASS system in prokaryotes and the cGAS–STING pathway in eukaryotes compare in antiviral defence?
Similarities:
- Both detect foreign DNA and produce cyclic dinucleotide signals
- Both use these signals to activate immune responses
CBASS (Prokaryotes):
- Triggered by phage infection
- Cyclase produces signaling molecules → activates effectors → causes cell suicide
- Goal: block phage replication by sacrificing infected cell
cGAS–STING (Eukaryotes):
- Triggered by viral dsDNA detection via cGAS
- cGAMP activates STING in ER membrane
- Leads to expression of antiviral genes (e.g. interferons), not immediate cell death
What is the Thoeris system? (3)
- Thoeris is a bacterial defence system that triggers abortive infection to block phage spread
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Key components:
– ThsB: Contains a TIR domain that senses phage infection
– ThsA: Effector with NADase activity
What is the Thoeris system mechanism? (5)
Mechanism:
1) Phage infection activates ThsB’s TIR domain
2) TIR domain synthesizes cADPR isomer (signalling molecule)
3) cADPR binds to SLOG domain of ThsA, activating it
4) Activated ThsA depletes NAD⁺, halting cellular processes and killing the host cell before phage can replicate
- Result: Abortive infection — the infected cell dies to protect the bacterial population
How do TIR domains function in prokaryotic and eukaryotic antiviral immunity? (5)
In prokaryotes (e.g. Thoeris system):
- ThsB uses NAD⁺ to produce a cADPR isomer upon phage infection
- This activates ThsA, depleting NAD⁺ and causing growth arrest or cell death
In eukaryotes (e.g. plants):
- TIR domains also use NAD⁺ to generate signalling molecules (e.g. v-cADPR)
- These trigger cell death or a hypersensitive immune response
- Suggests a shared evolutionary origin of TIR-based defence mechanisms in both domains of life
How do TIR domains influence the phage specificity of the Thoeris defence system? (2)
- Thoeris TIR domains determine which phages are targeted by the defence system
- Hosts can encode multiple TIR proteins (e.g. TIR1, TIR2) to expand their range of phage protection
What evolutionary scenario explains the conservation of immune mechanisms between prokaryotes and eukaryotes? (5)
- Eukaryotic immune systems may have originated from prokaryotic defences during an endosymbiotic event
- Early eukaryotes inherited defence genes from the prokaryotic ancestor(s) involved in this event
- Additional immune genes could be acquired via horizontal gene transfer
- Over time, eukaryotic immunity was diversified through:
– Domain shuffling
– Gene duplication
– De novo functional innovation
- This explains shared elements like TIR domains, gasdermins, and cGAS-STING across domains of life
How do some phages evade CBASS defence systems? (4)
- Phages encode Acb proteins that degrade cyclic nucleotide signals
- Prevents activation of CBASS effectors
- Example: Acb1 from phage T4 cleaves cyclic di- and tri-nucleotides
- Acb1 is conserved across diverse phage lineages
