A comprehensive pathophysiology diagram illustrating the three activation pathways of the human complement system—Alternative, Lectin, and Classical—and their convergence into the Terminal Pathway. The Classical pathway is initiated by C1q and C1r/s complexes, the Lectin pathway by MBL/Fcn/CL and MASP-1/2 complexes, and the Alternative pathway via spontaneous 'tickover' starting with C3b. The diagram details the formation of C3 convertases (C3bBb and C4b2b) and C5 convertases, leading to the terminal assembly of the Membrane Attack Complex (MAC, C5b-9) and the release of anaphylatoxins C3a and C5a. Superimposed on the biochemical cascade are clinical therapeutic targets and their respective inhibitors. 'Initiation Inhibitors' include Narsoplimab and Sutimlimab; 'Amplification Inhibitors' include Pegcetacoplan, Iptacopan, and Danicopan; and 'Effector Inhibitors' include Eculizumab, Ravulizumab, and Avacopan. This educational infographic serves as a guide for understanding complement-driven diseases and the pharmacological mechanisms of current and emerging biological treatments.

A comprehensive pathophysiology diagram illustrating the three activation pathways of the human complement system: Classical, Lectin, and Alternative. The Classical pathway is initiated by C1q (complexed with C1r2 and C1s2); the Lectin pathway utilizes MBL, ficolins, and collectin-11 with MASPs; and the Alternative pathway involves Properdin and C3(H2O) with Factors B and D. All three pathways converge at the enzymatic cleavage of C3 into C3a and C3b. The C4b2b complex (C3 convertase) is shown mediating this in the classical/lectin routes, while C3bBb performs this in the alternative route. The downstream cascade leads to C5 cleavage, producing the anaphylatoxin C5a and fragment C5b. Educational highlights include the assembly of the Membrane Attack Complex (MAC, C5b-9) depicted as a blue pore-forming structure, and the production of opsonins (iC3b, C3d). The diagram specifically contextualizes the immune response within the nervous system, showing receptors like C3aR, C5aR, and CR3 on glial-like cells, illustrating the role of complement in neuroinflammation or synaptic pruning.

A pathophysiology diagram illustrating the human complement system cascade, organized into three primary activation pathways: Classical, Lectin, and Alternative. The Classical pathway is shown initiating via C1q, C1r, and C1s to form an active C1q/r/s complex. The Lectin pathway begins with MBL and MASP1/2, forming an active MBL complex. Both pathways converge to cleave C4 and C2 into the C4b2a complex. The Alternative pathway depicts the spontaneous cleavage of C3 into C3a and C3b, the latter interacting with Factor B and Factor D to form C3bBb. These processes converge at the central C3 convertase node, which further cleaves C3 into C3a (anaphylatoxin) and C3b. The cascade proceeds to C5 convertase, which cleaves C5 into C5a (anaphylatoxin) and C5b. Terminal events include the assembly of C5b with C6, C7, C8, and C9 to form the Membrane Attack Complex (MAC) embedded in a lipid bilayer, leading to cell lysis. The diagram also highlights the role of C3a and C5a as anaphylatoxins that trigger an inflammatory response involving immune cell recruitment.

This pathophysiology diagram illustrates the three activation pathways of the human complement system: Classical, Lectin, and Alternative. The Classical pathway is triggered by antigen-antibody complexes, the Lectin pathway by PAMP recognition, and the Alternative pathway via spontaneous hydrolysis ('tick-over') involving Factors B and D. All three pathways converge at the activation of C3. Key downstream events include the cleavage of C3 into C3a (driving inflammation) and C3b (mediating opsonization). The diagram highlights an 'amplification loop' where C3b reinforces C3 activation, alongside regulatory mechanisms such as C3b breakdown by Factor I (FI) and Factor H (FH). The cascade progresses to C5 activation, resulting in C5a-mediated inflammation and the formation of the C5b-9 Membrane Attack Complex (MAC), which is regulated by CD59 and ultimately leads to cell lysis. The illustration serves as an educational summary of innate immune system proteolytic signaling, highlighting the balance between effector functions (inflammation, opsonization, lysis) and inhibitory regulation.