Figure 1: complement activation, regulation, and its biological effects when facing danger signal. In the presence of danger signals like DAMP and PAMP, complement is activated through three major pathways: the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP) to produce effector molecules, including opsonins (C3b, C4b, etc.), anaphylatoxins (C3a, C5a) and Membrane Attack Complex (MAC). C3a, C5a promote the recruitment of neutrophils, mast cells degranulation. And they bind to the specific receptors on macrophages and monocytes to promote inflammasome activation, proteases and reactive oxygen species releasing. MAC mediate P38/MAPK and NFκB signaling pathway and induce inflammasome activation and inflammatory cytokines production. Complement can also mediate a hypercoagulable state. C5a /C5aR1 interaction on endothelial cells and monocytes induces the tissue factor and adhesion molecules expression and promotes the coagulation pathway. C3a /C3aR interaction on platelets and primes its activation. MAC inserts into platelet membrane to promote platelet prothrombotic microvesicles releasing. Overall, complement activation can induce an “thrombo-inflammation” response and form a two-hit stress to host. Opsonins C3b/iC3b/C3d can bind to CR3/4 to promote antigen phagocytosis and presentation to T cells. CR2 bind to C3d modified antigen peptides to promote B cell activation and specific antibody production. MAC insert into cell surface to lyse the damaged or infected cells. These effectors organized to promote the timely removal of danger signals. Neutrophil (N); Macrophages (Mφ); Monocytes (Mo); Lymphocytes (L); Dendritic cells (DC); Endothelial cells (EC); Mast cell (MC); Platelet (P); Antigen (Ag); Adaptive immune (AI).