Describe the classical complement cascade pathway from C1 to the MAC.

Verified step by step guidance

1. Start by explaining that the classical complement pathway is initiated when the C1 complex binds to antibodies (IgG or IgM) that are attached to antigens on a pathogen surface. The C1 complex consists of C1q, C1r, and C1s subunits.
2. Next, describe how the binding of C1q to the antibody activates C1r, which then activates C1s. Activated C1s cleaves C4 into C4a and C4b, and C2 into C2a and C2b.
3. Explain that C4b binds covalently to the pathogen surface and then binds C2a, forming the C3 convertase complex (C4b2a). This enzyme complex cleaves C3 into C3a and C3b.
4. Describe how C3b binds to the C3 convertase to form the C5 convertase complex (C4b2a3b), which cleaves C5 into C5a and C5b. C5b initiates the assembly of the membrane attack complex (MAC).
5. Finally, outline the formation of the MAC by sequential binding of C6, C7, C8, and multiple C9 molecules to C5b, creating a pore in the pathogen membrane that leads to cell lysis.

Key Concepts

Classical Complement Pathway Initiation

The classical pathway begins when the C1 complex (composed of C1q, C1r, and C1s) binds to antibodies attached to antigens on a pathogen surface. This binding activates C1r and C1s, which then cleave C4 and C2, forming the C3 convertase (C4b2a). This step links adaptive immunity with complement activation.

Formation and Function of C3 Convertase

C3 convertase (C4b2a) cleaves C3 into C3a and C3b. C3b binds to the pathogen surface and to the convertase itself, forming C5 convertase (C4b2a3b). This enzyme complex is crucial for amplifying the response and initiating the terminal pathway leading to membrane attack complex formation.

Membrane Attack Complex (MAC) Assembly

The MAC forms when C5 convertase cleaves C5 into C5a and C5b. C5b sequentially recruits C6, C7, C8, and multiple C9 molecules, creating a pore in the pathogen's membrane. This pore disrupts membrane integrity, causing cell lysis and death, effectively eliminating the target microbe.