Complement activation pathways MCQs With Answer

Introduction: This set of MCQs on complement activation pathways is designed for M.Pharm students to deepen understanding of the classical, lectin and alternative arms of the complement system, their molecular components, regulators, and clinical relevance. Questions focus on mechanistic details such as convertase formation, cleavage sites, amplifying loops, and membrane attack complex assembly, as well as complement assays, regulatory proteins and therapeutic interventions. The quiz emphasizes integration of biochemical steps with pharmacological and pathological implications—useful for exam preparation and applied research. Answers are provided to facilitate self-assessment and reinforce critical concepts necessary for advanced study and clinical translation in immunotechnology.

Q1. Which of the following best describes the initial recognition molecule of the classical complement pathway?

• C1q binding to Fc regions of IgG or IgM in immune complexes
• Mannose-binding lectin binding to pathogen-associated mannose residues
• Spontaneous hydrolysis of C3 to C3(H2O) on microbial surfaces
• Properdin binding directly to pathogen polysaccharides to initiate activation

Correct Answer: C1q binding to Fc regions of IgG or IgM in immune complexes

Q2. Which pair of proteases constitutes the C1 complex proteolytic activity in the classical pathway?

• C1r and C1s
• C2a and C4b
• Factor B and Factor D
• C3b and Bb

Correct Answer: C1r and C1s

Q3. The lectin pathway is most directly activated by which mechanism?

• Mannose-binding lectin-associated serine proteases (MASPs) cleaving C4 and C2 after MBL binds carbohydrate patterns
• IgE cross-linking on basophils leading to complement deposition
• Spontaneous C3 tick-over followed by properdin stabilization
• Membrane attack complex formation on host cells

Correct Answer: Mannose-binding lectin-associated serine proteases (MASPs) cleaving C4 and C2 after MBL binds carbohydrate patterns

Q4. In the alternative pathway, which enzyme cleaves Factor B when it is bound to C3b to form the C3 convertase?

• Factor D
• Factor I
• Factor H
• Properdin

Correct Answer: Factor D

Q5. What is the enzymatic composition of the classical and lectin pathway C3 convertase?

• C4b2a
• C3bBb
• C5b67
• C1qrs

Correct Answer: C4b2a

Q6. Which complement fragment is the main opsonin that promotes phagocytosis by binding complement receptors on phagocytes?

• C3b
• C3a
• C5a
• C9

Correct Answer: C3b

Q7. Which of the following describes the formation of the membrane attack complex (MAC)?

• Sequential binding of C5b, C6, C7, C8 and multiple C9 molecules to form a pore in target membranes
• Aggregation of C3a and C5a to form a membrane-disrupting complex
• Polymerization of C4b and C2a to insert into microbial membranes
• Binding of properdin and Factor B to create a transmembrane channel

Correct Answer: Sequential binding of C5b, C6, C7, C8 and multiple C9 molecules to form a pore in target membranes

Q8. Which complement fragments function as anaphylatoxins and rapidly induce chemotaxis and increased vascular permeability?

• C3a and C5a
• C3b and iC3b
• C4b and C2a
• C5b and C6

Correct Answer: C3a and C5a

Q9. Factor H regulates the alternative pathway by which primary mechanism?

• Competing with Factor B for C3b binding and acting as a cofactor for Factor I-mediated C3b cleavage
• Accelerating formation of C3 convertase C4b2a
• Directly cleaving C5 into C5a and C5b
• Binding to C1q to prevent classical pathway initiation

Correct Answer: Competing with Factor B for C3b binding and acting as a cofactor for Factor I-mediated C3b cleavage

Q10. Properdin’s role in the alternative pathway is primarily to:

• Stabilize the C3bBb convertase on microbial surfaces
• Cleave C3 into C3a and C3b
• Act as an opsonin independent of convertases
• Inhibit MAC formation on host cells

Correct Answer: Stabilize the C3bBb convertase on microbial surfaces

Q11. A deficiency of terminal complement components C5–C9 most commonly increases susceptibility to which type of infection?

• Neisseria species (meningococcal and gonococcal infections)
• Opportunistic fungal infections such as Candida
• Intracellular bacteria like Listeria
• Chronic helminth infections

Correct Answer: Neisseria species (meningococcal and gonococcal infections)

Q12. Which laboratory assay measures the functional activity of the classical complement pathway?

• CH50 assay (total hemolytic complement activity)
• AH50 assay
• ELISA for factor B
• C3a quantification by mass spectrometry

Correct Answer: CH50 assay (total hemolytic complement activity)

Q13. Which membrane-bound regulator prevents formation of the MAC by inhibiting C9 polymerization on host cells?

• CD59 (protectin)
• Decay-accelerating factor (DAF, CD55)
• CR1 (CD35)
• Complement receptor 2 (CR2, CD21)

Correct Answer: CD59 (protectin)

Q14. Eculizumab, a therapeutic monoclonal antibody, exerts its effect by binding to which complement component?

• C5
• C3
• C1q
• Factor D

Correct Answer: C5

Q15. Which statement best explains the “tick-over” mechanism in complement activation?

• Spontaneous low-rate hydrolysis of C3 to C3(H2O) that allows alternative pathway initiation in fluid phase
• Induced cleavage of C4 by MASP-2 following lectin binding
• Rapid polymerization of C9 on microbial membranes
• Antibody-dependent activation of C1q on immune complexes

Correct Answer: Spontaneous low-rate hydrolysis of C3 to C3(H2O) that allows alternative pathway initiation in fluid phase

Q16. CR1 (CD35) on erythrocytes primarily contributes to immune complex handling by:

• Binding C3b-opsonized complexes and transporting them to the liver and spleen for clearance
• Acting as a receptor for anaphylatoxins to recruit neutrophils
• Directly lysing microbes via MAC assembly
• Inhibiting Factor I activity on cell surfaces

Correct Answer: Binding C3b-opsonized complexes and transporting them to the liver and spleen for clearance

Q17. Which complement component is directly cleaved to generate the potent chemoattractant C5a?

• C5 by C5 convertase
• C3 by C3 convertase
• C4 by C1s
• C2 by MASP-2

Correct Answer: C5 by C5 convertase

Q18. In atypical hemolytic uremic syndrome (aHUS), which complement regulator is most commonly implicated by mutations or autoantibodies?

• Factor H
• CD59
• C1 inhibitor (C1-INH)
• Properdin

Correct Answer: Factor H

Q19. The alternative pathway provides amplification of complement activation because:

• C3b generated by any pathway can form additional C3 convertases (C3bBb) leading to exponential C3 cleavage
• It exclusively generates C5a without producing C3b
• Properdin directly cleaves C3 into C3a and C3b causing rapid activation
• Lectin pathway MASPs recruit Factor B to amplify activity

Correct Answer: C3b generated by any pathway can form additional C3 convertases (C3bBb) leading to exponential C3 cleavage

Q20. Which complement assay is specifically used to assess the functional integrity of the alternative pathway?

• AH50 assay (alternative pathway hemolytic assay)
• CH50 assay
• Western blot for C1q
• ELISA for C4d

Correct Answer: AH50 assay (alternative pathway hemolytic assay)

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