The classical pathway is one of three pathways that activate the complement system, a crucial part of the innate immune system that helps recognize and eliminate invading pathogens. The classical pathway is primarily activated by antibodies that bind to antigens on the surface of a pathogen. This pathway consists of a series of sequential steps that result in the formation of the membrane attack complex, leading to the lysis of the pathogen. Here are the steps involved in the classical pathway:

Step 1: Initiation

1. Antigen-antibody complexes form when antibodies recognize and bind to antigens on the surface of a pathogen.
2. The Fc region of the antibody becomes exposed and binds to the complement component C1q.

Step 2: Activation of C1

1. Binding of C1q to the Fc region of the antibody leads to the activation of the C1 complex, which consists of C1q, C1r, and C1s.
2. C1r cleaves and activates C1s, which then cleaves C4 and C2.

Step 3: Formation of C3 convertase

1. The cleavage of C4 and C2 leads to the formation of the C3 convertase complex, C4b2a.
2. C3 convertase cleaves C3 into C3a and C3b.

Step 4: Amplification of the complement cascade

1. C3b binds to the pathogen surface and can initiate the alternative pathway by binding factor B, which is cleaved by factor D to form C3bBb, the alternative pathway C3 convertase.
2. C3b also binds to C4b2a to form the classical pathway C5 convertase, C4b2a3b.

Step 5: Formation of membrane attack complex (MAC)

1. C5 convertase cleaves C5 into C5a and C5b.
2. C5b initiates the formation of the membrane attack complex (MAC) by binding to C6, C7, C8, and multiple copies of C9 to form a pore on the pathogen’s membrane, leading to lysis.

Overall, the classical pathway of the complement system plays an essential role in the recognition and elimination of pathogens that are opsonized by antibodies. By activating a cascade of complement proteins, the classical pathway generates effector molecules that can attract and activate immune cells, lyse pathogens, and promote phagocytosis.