Cascades
Pick a lesson, then walk its steps. Each step opens the mechanism, what fails if that component is absent, and the clinical read-out.
Immunology Academy · foundation track
One navigable beginner path through existing Mechanism lessons. Teaching simplifications are labelled; claim-level Gate C coverage is separate and may still be sparse. Progress is stored in this browser only — we do not claim course completion, certification, or Gate C evidence coverage.
Track status: navigable · Local quiz checks 0/6 · Lessons opened 0/3
- 1. not opened yetInnate sensing (TLR4 → NF-κB)
Trace LPS recognition to NF-κB-driven inflammatory transcription.
- 2. not opened yetCytokine networks (IL-6 chain)
Explain classical vs trans IL-6 signalling at a teaching level.
- 3. not opened yetInflammation effector (NLRP3 → IL-1β)
State the two-signal requirement for IL-1β release.
Inflammation effector (NLRP3 → IL-1β)
NLRP3/IL-1 teaching path is scaffolded from existing lessons; Gate C approved support is not implied by finishing the track.
Objectives
- State the two-signal requirement for IL-1β release.
- Link caspase-1 / gasdermin D to pyroptotic release.
- Give one example of crystal-driven NLRP3 activation.
Teaching simplifications
- Diverse NLRP3 triggers are collapsed to K⁺ efflux / damage motifs.
- CANTOS secondary signals are hypothesis-generating, not Academy proof.
Graph concepts
Check understanding
Local practice only — not a credential, not SME sign-off, not evidence approval.
Why does productive IL-1β release usually need two signals?
Which stimulus class is a classic NLRP3 activator in gout?
NLRP3 inflammasome: two signals to IL-1β
Why does a cell need two separate signals before releasing IL-1β?
Perturbation experiments
Break one component and follow the consequence chain to the clinical read-out.
Target: NLRP3 (CAPS)
- NLRP3 assembles with minimal signal 2 (even cold exposure)
- Constitutive caspase-1 activity
- Excess IL-1β → fever, urticarial rash, arthralgia, meningitis
- Chronic disease → amyloidosis, sensorineural hearing loss
Clinical read-out. CAPS (FCAS → Muckle–Wells → NOMID) responds dramatically to anakinra, canakinumab or rilonacept, proof IL-1β is the effector.
Target: IL-1β in the TME
- IL-1β promotes angiogenesis, MDSC recruitment and tumour-promoting inflammation
- Neutralising IL-1β altered the tumour-supportive milieu
- Lung-cancer incidence and mortality fell in a secondary analysis
- Prospective trials (CANOPY) did not confirm benefit in established NSCLC
Clinical read-out. A lesson in hypothesis generation: unexpected secondary signals need their own trials.
Target: IL-1β redundancy
- IL-1α, TNF, IL-6 and IFN responses remain
- Neutrophil recruitment partly preserved via CXCL8
- CANTOS saw more fatal infections (small absolute increase)
- Redundancy limits but does not remove risk
Clinical read-out. Screen for infection risk; avoid live vaccines on IL-1 blockade.