Q53.Arrange the following components of complement system as per their involvement in initiation of alternative pathways of complement system.
A. Factor D
B. Factor B
C. C3b
D. Properdin
Choose the correct answer from the options given below :
(1) C, A, B, D
(2) A, C, B, D
(3) A, B, C, D
(4) D, C, B, A
The correct sequence for initiation of the alternative complement pathway is C, A, B, D (option 1). This follows the precise biochemical cascade where C3 activation triggers subsequent factor involvement.
Correct Sequence
The alternative pathway begins spontaneously with C3 hydrolysis or surface deposition, then proceeds as follows in eukaryotes:
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C. C3b: Spontaneous hydrolysis of C3 forms C3(H₂O), which binds surfaces; C3b deposits and recruits Factor B.
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A. Factor D: Serine protease Factor D cleaves Factor B into Ba and Bb while bound to C3b.
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B. Factor B: Cleaved Bb associates with C3b to form the initial C3 convertase (C3bBb).
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D. Properdin: Stabilizes the C3bBb complex, extending its half-life for amplification.
This creates an amplification loop leading to opsonization, inflammation, and membrane attack complex formation.
Why Other Options Fail
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Option 2 (A, C, B, D): Wrong; Factor D (A) cannot act before C3b (C) provides the binding site for Factor B.
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Option 3 (A, B, C, D): Wrong; Factors A/B precede C3b in this order, but C3b deposition initiates the cascade.
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Option 4 (D, C, B, A): Wrong; Properdin (D) stabilizes the later complex, not initiates; Factor D (A) acts before properdin.
Introduction to Alternative Pathway Sequence
Mastering the alternative pathway complement system sequence—starting with C3b, then Factor D, Factor B, and Properdin—is essential for immunology exams like NEET. This antibody-independent pathway provides rapid innate immunity against pathogens.
Step-by-Step Cascade
The initiation unfolds in the plasma or on pathogen surfaces:
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C3b (C): C3 hydrolyzes to C3(H₂O); thioester exposes C3b for surface binding.
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Factor D (A): Cleaves Factor B (Mg²⁺-dependent) into Bb (serine protease) and Ba.
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Factor B (B): Bb binds C3b, forming unstable C3 convertase (C3bBb).
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Properdin (D): Binds and stabilizes C3bBb, enabling C3 cleavage amplification.
Exam Mistakes to Avoid
Options reversing C3b or placing properdin early confuse initiation with stabilization. Remember: C3b seeds the complex.
Biological Relevance
This alternative pathway complement system sequence amplifies responses in infections, autoimmunity, and therapies targeting complement deficiencies.
