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Immunology · USMLE Step 1

USMLE Immunology: Complement System

Classical, alternative, and lectin complement pathways and the deficiency disorders tied to each component tested on USMLE Step 1.

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Which complement protein is the first to be activated in the classical pathway?
C1q
What directly triggers activation of the classical complement pathway?
Antigen-antibody (immune) complexes binding C1q
Which antibody isotype is the most efficient activator of the classical complement pathway?
IgM
IgM is a more efficient activator of the classical complement pathway than IgG because IgM's ____ structure can bind multiple C1q heads at once.
pentameric
What is the C3 convertase of the classical pathway?
C4b2a
What triggers activation of the lectin complement pathway?
Mannose-binding lectin (MBL) binding mannose residues on a pathogen surface
Which enzymes does mannose-binding lectin activate to drive the lectin pathway?
MASPs (MBL-associated serine proteases)
What triggers activation of the alternative complement pathway?
Spontaneous hydrolysis of C3 on a microbial surface, without antibody
What is the C3 convertase of the alternative pathway?
C3bBb
Which protein stabilizes the alternative pathway's C3 convertase?
Properdin (factor P)
Which protein binds C3b and is then cleaved by factor D in the alternative pathway?
Factor B
What is the C5 convertase formed by the classical and lectin pathways?
C4b2a3b
What is the C5 convertase formed by the alternative pathway?
C3bBb3b
Which complement proteins make up the membrane attack complex?
C5b-9
What is the main function of the membrane attack complex?
It lyses the pathogen cell membrane, especially gram-negative bacteria like Neisseria

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