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. Draft extension lessons are labelled — not curated core.
Immunology Academy
Foundation is a navigable teaching scaffold; intermediate is an honest in-development scaffold over existing Mechanism lessons; advanced is labelled empty. Progress stays in this browser — not certification, not Gate C evidence coverage. Academy overview
Foundation: innate sensing → cytokines → inflammation
foundation · navigable scaffoldOne navigable beginner path through existing Mechanism lessons. Teaching simplifications are labelled; claim-level Gate C coverage is separate and may still be sparse.
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.
Intermediate: adaptive brakes, IFN sensing, type-2 effectors
intermediate · in development · scaffold onlyHonest scaffold over three existing Mechanism lessons (checkpoint, cGAS–STING, type-2). Not a finished intermediate curriculum — labelled in development; local quizzes only.
Local quiz checks 0/5 · Lessons opened 0/3 · In development
- 1. not opened yetCheckpoints at the synapse (CTLA-4 / PD-1)
Contrast CTLA-4 (priming) vs PD-1 (peripheral brake) as a teaching scaffold.
- 2. not opened yetCytosolic DNA → type I IFN (cGAS–STING)
Trace cytosolic DNA to IFNAR-driven ISG programmes at teaching depth.
- 3. not opened yetType-2 effectors (alarmins → asthma teaching path)
Place TSLP/IL-33 alarmins upstream of ILC2/Th2 teaching cascades.
Checkpoints at the synapse (CTLA-4 / PD-1)
Checkpoint teaching path is educational. Live Gate C on PD-1 exemplar edges may still be partial — finishing this module is not claim review.
Objectives
- Contrast CTLA-4 (priming) vs PD-1 (peripheral brake) as a teaching scaffold.
- Name one toxicity-pattern difference that follows from where each acts.
- State why MHC-I loss can blunt anti-PD-1 response without inventing patient advice.
Teaching simplifications
- Synapse timing is simplified; real tumours and autoimmunity diverge.
- Trial response rates are context, not Academy proof of Gate C.
Graph concepts
Check understanding
Local practice only — not a credential, not SME sign-off, not evidence approval.
Advanced: systems integration (scaffold)
advanced · in development · scaffold onlyPlaceholder for multi-pathway integration lessons. No modules are navigable yet — labelled scaffold only, not a finished advanced course or certification.
Local quiz checks 0/0 · Lessons opened 0/0 · In development
Immunological synapse: co-stimulation and checkpoints
Why do anti-CTLA-4 and anti-PD-1 work in different places and cause different toxicities?
Perturbation experiments
Break one component and follow the consequence chain to the clinical read-out.
Target: MHC-I / B2M loss
- CD8 T cells can no longer see tumour peptides
- PD-1 blockade reinvigorates T cells that have nothing to kill
- Acquired resistance emerges
- But missing-self now activates NK cells
Clinical read-out. B2M mutations are a recognised mechanism of resistance; NK-directed strategies are being explored.
Target: CTLA-4 vs PD-1
- CTLA-4 acts early, in lymph nodes, on many clones
- Treg suppression in gut depends heavily on CTLA-4
- Blockade broadly lowers the priming threshold
- Gut-reactive clones expand → colitis
- PD-1 acts later, locally, on already-activated cells
Clinical read-out. Grade 3–4 irAEs: ~55–60% with nivolumab + ipilimumab vs ~20% with nivolumab alone (CheckMate 067).