What initiates the classical pathway of complement activation?

The classical pathway of complement activation begins with the binding of the C1 complex to an antigen-antibody (Ag-Ab) complex. This binding is crucial because it leads to a conformational change in the C1 complex, which is made up of C1q, C1r, and C1s proteins. Once C1 binds to the Ag-Ab complex, it becomes activated and cleaves C4 and C2 proteins, forming the C3 convertase of the classical pathway, which then leads to a series of subsequent reactions involved in opsonization, inflammation, and cell lysis.

In contrast, the initiation methods proposed by the other choices refer to different mechanisms or pathways. For example, C3 binding to an Ag-Ab complex does not initiate the classical pathway; instead, it represents a step that occurs later in the complement cascade once the pathway has been activated. Factor B's role is primarily associated with the alternative pathway, where it binds to the activated form of C3. Lastly, the formation of the membrane attack complex (MAC) occurs at the end stages of complement activation, not at the initiation phase, and it plays a role in directly lysing pathogens rather than signaling the start of the pathway.