Question

Arrange the following events of complement classical pathway in correct order:
A. Formation of membrane attack complex
B. Binding of C1 to antibody-antigen complex
C. Cleavage of C3
D. Formation of C5 convertase

• A. B $\rightarrow$ C $\rightarrow$ D $\rightarrow$ A
• B. C $\rightarrow$ B $\rightarrow$ D $\rightarrow$ A
• C. B $\rightarrow$ D $\rightarrow$ C $\rightarrow$ A
• D. D $\rightarrow$ B $\rightarrow$ C $\rightarrow$ A

Hint:

Remember the general flow of complement pathways: Initiation $\rightarrow$ C3 convertase $\rightarrow$ C5 convertase $\rightarrow$ MAC. The defining starting point for the \textit{classical} pathway is always antibody binding (C1 complex activation).

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
The classical complement pathway is an immune mechanism triggered typically by the binding of antibodies to antigens, leading to a cascade of proteolytic cleavage events that ultimately destroy the target cell.

Step 2: Detailed Explanation:
The sequential steps of the classical complement pathway occur in a highly regulated order.
1. Initiation: The pathway begins when the C1 complex binds to the Fc portion of antibodies (IgM or IgG) that are bound to an antigen.
This is event B (Binding of C1 to antibody-antigen complex).
2. C3 Convertase Formation \& Cleavage of C3: C1 activation leads to the cleavage of C4 and C2 to form the C3 convertase (C4b2a).
The C3 convertase then cleaves multiple C3 molecules into C3a and C3b.
This corresponds to event C (Cleavage of C3).
3. C5 Convertase Formation: Some of the generated C3b binds to the existing C3 convertase to form the C5 convertase (C4b2a3b).
This is event D (Formation of C5 convertase).
4. Terminal Pathway (MAC Formation): The C5 convertase cleaves C5, initiating the recruitment of C6, C7, C8, and C9 to form the membrane attack complex (MAC).
This creates a pore in the target cell membrane, corresponding to event A (Formation of membrane attack complex).

Step 3: Final Answer:
Therefore, the correct chronological sequence is B $\rightarrow$ C $\rightarrow$ D $\rightarrow$ A.
This matches option (A).