Complement Cascade Tournament
Two onboarding diagrams orient you in the complement system. Then eight MCAT-DoK quiz rounds: C3 as the master node, C1 inhibitor and hereditary angioedema, the canonical classical-pathway sequence, opsonization vs. anaphylatoxin vs. MAC roles, the three activation pathways, regulation + Neisseria infections, complement vs. clotting nomenclature, and PNH / eculizumab.
Where the Complement cascade fits in Innate Immune System
Complement is one of the most ancient innate immune effector systems: ~30 proteins that opsonize pathogens, recruit phagocytes via anaphylatoxins, and lyse gram-negative bacteria via the membrane attack complex. Three activation routes converge on the same downstream effects. Click the highlighted Complement cascade box to enter the tournament.
Click the highlighted Complement cascade 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 complement within Reactome's Innate Immune System map.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways complement figure before you start answering.
Fill in the Blank
Recall C3 convertase as the central node where all three pathways converge.
Disruptor
Recognize hereditary angioedema as a bradykinin (NOT histamine) -mediated disorder of C1-INH loss.
Sequence Ordering
Trace the classical pathway from antibody-C1q binding to MAC insertion.
Match the Pairs
Pair C3b, C3a/C5a, MAC, MBL, properdin, DAF/CD59, and eculizumab with their roles.
Numeric Input
Recall the three convergent activation pathways.
Select All That Apply
Identify TRUE facts about anaphylatoxins, late-component deficiencies, immune complex clearance, and PNH.
Odd One Out
Distinguish Factor IX (clotting) from complement components.
PNH Disruptor
Recognize PIGA mutations and CD55/CD59 loss as the molecular basis of complement-mediated hemolysis.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
Complement in 60 seconds
Complement = ~30 proteins that opsonize pathogens (C3b), recruit inflammation (C3a, C5a), and lyse gram-negative bacteria (MAC = C5b-C9). Three activation routes: classical (antibody), lectin (MBL), alternative (spontaneous).
All three converge on C3 convertase, which cleaves C3 to C3a + C3b. Then C3b joins to form C5 convertase, which cleaves C5 -> C5a + C5b. C5b nucleates the membrane attack complex (C5b6789ₙ).
Regulation: DAF (CD55) + CD59 are GPI-anchored brakes on host cells. C1 inhibitor regulates classical pathway + the kallikrein-kinin system; loss = hereditary angioedema (bradykinin-mediated). Factor H brakes alternative pathway; mutations cause atypical HUS and contribute to age-related macular degeneration.
Disease patterns: early classical components (C1q, C2, C4) -> SLE-like autoimmunity (immune complex clearance defect); late components (C5-C9) -> Neisseria infections; PNH (PIGA mutation) -> loss of CD55/CD59 -> uncontrolled MAC on RBCs -> hemolysis. Eculizumab (anti-C5) blocks terminal complement.
FAQ
Why do eculizumab patients require meningococcal vaccination?
Eculizumab blocks C5 cleavage -> no C5b -> no MAC. Neisseria meningitidis is uniquely sensitive to MAC-mediated lysis (most other bacteria have envelope strategies that resist MAC). Patients with terminal complement deficiency or on eculizumab have markedly increased meningococcal disease risk; vaccination is mandatory before starting therapy.
Why does C1 inhibitor deficiency NOT respond to antihistamines?
Hereditary angioedema is BRADYKININ-mediated, not histamine-mediated. C1-INH normally restrains kallikrein, which generates bradykinin from kininogen. Loss of C1-INH -> excess bradykinin -> capillary leak. Treatment: replace C1-INH (Berinert), block kallikrein (ecallantide), or block the bradykinin B2 receptor (icatibant).
How are immune complexes cleared by complement?
C3b binds immune complexes; CR1 on erythrocytes binds C3b-tagged complexes and shuttles them to liver and spleen for phagocytic clearance. Defects in early classical components (C1q most strongly) impair this clearance, leading to immune complex deposition in skin, joints, kidneys - the SLE phenotype.
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 sensor system - PAMPs / DAMPs and TLR -> NF-κB cytokine production.
Complement and coagulation share factor naming + cross-talk; the kallikrein-kinin system links both.
Overview diagram: Reactome Pathway R-HSA-168249, licensed CC BY 4.0.