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.
Cytokine networks (IL-6 chain)
IL-6 biology here is educational. Approved claim cites for specific edges may be missing — do not treat quiz completion as evidence review.
Objectives
- Explain classical vs trans IL-6 signalling at a teaching level.
- Connect IL-6–STAT3 to acute-phase and Th17/Treg context.
- State why CRP can be misleading under IL-6R blockade.
Teaching simplifications
- One cytokine chain is highlighted; disease context changes outcomes.
- JAK inhibitors hit more than IL-6 alone.
Graph concepts
Check understanding
Local practice only — not a credential, not SME sign-off, not evidence approval.
What mainly enables IL-6 pro-inflammatory signalling on cells that lack membrane IL-6R?
Why can CRP stay low during infection in a patient on tocilizumab?
Cytokine network: IL-6 as a complete chain
Why does blocking the same cytokine produce different outcomes in different diseases?
Perturbation experiments
Break one component and follow the consequence chain to the clinical read-out.
Target: IL-6R blockade
- Hepatocyte CRP synthesis depends on IL-6–STAT3
- Tocilizumab blocks IL-6R on hepatocytes
- CRP stays low despite bacterial infection
- Fever is also blunted
- Clinicians lose two of their main infection alarms
Clinical read-out. Rely on clinical signs, procalcitonin (partially), imaging and cultures in patients on IL-6 blockade.
Target: IL-6R in CRS
- CAR-T cells recognise target → release IFN-γ, GM-CSF
- Monocytes/macrophages respond with massive IL-6
- IL-6 trans-signalling on endothelium → capillary leak, hypotension
- Tocilizumab blocks IL-6R → CRS resolves
- CAR-T cytotoxicity (perforin/granzyme, CD3ζ signalling) does not require IL-6
Clinical read-out. Tocilizumab is first-line for grade ≥2 CRS; it does not cross the blood–brain barrier well, so ICANS often needs corticosteroids.
Target: sgp130Fc (olamkicept)
- Soluble gp130 binds IL-6/sIL-6R complexes only
- Classical hepatocyte signalling is preserved
- Acute-phase and regenerative functions continue
- Inflammatory trans-signalling on gp130+ cells is removed
Clinical read-out. Olamkicept showed signals in IBD, a mechanistic attempt to separate benefit from infection risk.