Innate Immunity & TLR Signaling Tournament
Two onboarding diagrams orient you in innate immunity. Then eight MCAT-DoK quiz rounds: TLR4 / LPS recognition (CD14 + MD-2), the MyD88 -> IRAK -> TRAF6 -> IKK -> NF-κB axis, the canonical TLR4 signaling sequence, PRR distribution and ligands, the 10 human TLRs, NK cells + DAMPs + interferons, TCR vs PRR, and the molecular basis of septic shock hypotension.
Where the Toll-like receptor cascades fits in Innate Immune System
TLRs are the prototype pattern-recognition receptors of innate immunity - the cell-surface and endosomal receptors that recognize conserved microbial molecules (PAMPs). They drive NF-κB-dependent cytokine production and type I interferon responses. Click the highlighted Toll-like receptor cascades box to enter the tournament.
Click the highlighted Toll-like receptor cascades box to continue.
What this tournament tests
Each task maps to a distinct MCAT cognitive demand. The first two orient you in the broader topology; the next eight test the high-yield mechanism, regulation, sequence and quantitative reasoning that consistently appear on test day.
The Bigger Picture
Anchor TLR signaling within Reactome's Innate Immune System map.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways TLR signaling figure before you start answering.
Fill in the Blank
Recall LPS as the TLR4 ligand and the role of CD14 + MD-2.
Disruptor
Predict why LPS-driven TLR4 -> NF-κB activation produces septic shock cytokine storm.
Sequence Ordering
Trace LPS -> CD14/MD-2/TLR4 -> MyD88 -> IRAK4/1 -> TRAF6 -> TAK1 -> IKK -> NF-κB.
Match the Pairs
Pair each TLR (3, 4, 9), adaptor (MyD88, TRIF), inflammasome, and RIG-I with its precise role.
Numeric Input
Recall the number of human TLRs (10).
Select All That Apply
Identify TRUE facts about innate immunity, NK cells, complement, DAMPs, and trained immunity.
Odd One Out
Distinguish the T-cell receptor (adaptive) from PRRs (innate).
Septic Shock Disruptor
Recognize iNOS-driven NO vasodilation as the molecular basis of distributive shock.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
Innate immunity and TLR signaling in 60 seconds
Innate immunity uses germline-encoded pattern-recognition receptors (PRRs) to detect conserved microbial signatures (PAMPs) and damage signals (DAMPs). The major PRR classes: surface TLRs, endosomal TLRs, cytosolic NLRs (e.g. NLRP3), cytosolic RNA sensors (RIG-I / MDA5), and C-type lectins.
The TLR signaling spine: TLR -> MyD88 -> IRAK -> TRAF6 -> TAK1 -> IKK -> IκB phospho-degradation -> NF-κB. NF-κB drives transcription of TNF-α, IL-1β, IL-6, COX-2 - the cytokine storm of inflammation. TLR3 + TLR4-TRIF use a parallel branch to IRF3 -> type I interferons.
Each TLR has a defined ligand: TLR2 (LTA), TLR3 (dsRNA), TLR4 (LPS), TLR5 (flagellin), TLR7/8 (ssRNA), TLR9 (CpG DNA). Surface TLRs catch extracellular pathogens; endosomal TLRs catch internalized nucleic acids.
Septic shock = TLR4 cytokine storm + iNOS + NO -> profound vasodilation -> distributive shock. Inflammasome activation (NLRP3) requires two signals (NF-κB priming + assembly trigger), producing caspase-1-cleaved IL-1β. Cryopyrin-associated periodic syndromes (CAPS) treated with anakinra / canakinumab.
FAQ
Why doesn't TLR9 trigger autoimmunity against the host's own DNA?
TLR9 is restricted to ENDOSOMES (not surface) and recognizes UNMETHYLATED CpG motifs - characteristic of bacterial / viral DNA. Mammalian DNA is heavily CpG-methylated and is not delivered to endosomes. Failure of these compartmentalization rules contributes to lupus-like autoimmunity.
How does NLRP3 inflammasome activation differ from TLR signaling?
NLRP3 is CYTOSOLIC and activates caspase-1, which proteolytically cleaves pro-IL-1β + pro-IL-18 to active forms (and cleaves gasdermin D for pyroptosis). It needs TWO signals: priming (NF-κB makes pro-IL-1β) and a trigger (K+ efflux, mitochondrial damage, crystals). TLRs alone don't produce mature IL-1β - the inflammasome step is essential.
Why are anti-TNF biologics so effective in inflammatory diseases?
TNF-α is downstream of NF-κB and amplifies the entire inflammatory cascade through autocrine/paracrine signaling. Blocking it (infliximab, adalimumab) breaks the feed-forward loop in rheumatoid arthritis, IBD, psoriasis, etc. The price: increased risk of reactivation TB and certain infections.
Do I need an account to play?
No. The tournament is fully public. You get a randomized handle and your score posts to the public leaderboard at the bottom of this page.
Keep going
The other major innate immune effector system - opsonization, MAC, and C3 convertase logic.
Programmed cell death intersects innate immunity through pyroptosis and inflammasome biology.
Overview diagram: Reactome Pathway R-HSA-168249, licensed CC BY 4.0.