Complement: The Alternative Pathway

Abstract

The alternative pathway of complement is a powerful and evolutionarily old defence system of innate immunity that recognises and destroys invading infectious microbes and also targets and eliminates modified self cells. For survival in an immunocompetent host, pathogenic microbes provide strategies to interfere with alternative pathway activation at their surface and they evade complement immune recognition. Recent evidence shows that mutations and sequence variations of important regulators of the alternative pathway cause a variety of autoimmune diseases, including age‐related macular degeneration (AMD) of the retina and kidney diseases in the form of atypical haemolytic uraemic syndrome (aHUS) and C3 glomerulopathy (C3G). On the basis of its central relevance in immunity targeting, the complement system by specific therapeutic agents is a promising approach to treat autoimmune diseases and inflammatory disorders. Key Concepts Alternative pathway is a spontaneous self‐amplifying initiator of complement AP is activated by default in blocked by inhibitors Defective AP regulation results in serve autoimmune disease Mutations in regulators and autoimmune forms cause diseases Pathogenic infectious microbes block AP action by mimicking intact host surfaces The C3 convertase of the AP is the central hub for complement activation AP is controlled in fluid phase and on biological surfaces Targeting AP action is a promising option to treat inflammatory autoimmune disorders Animal behaviourists must participate in conservation planning to protect the future of biodiversity Lipid bilayers provide the fundamental architecture of biological membranes.

Molecular crypsis by pathogenic fungi using human factor H. A numerical model

“…The presented model analyses the initial phase of activation of the alternative pathway of the human complement system [20]. The complement system is a part of innate immunity, which is not adaptable and does not change over the course of an individual’s lifetime.…”

“…Key factors of the complement system are FH together with complement component 3 (C3) [20]. Both are continuously present at high concentrations in the blood.…”

Electrostatic Steering Accelerates C3d:CR2 Association

“…All three pathways converge at complement component C3. 34 Complement C3 undergoes a series of cleavage steps that activate, inactivate, and redirect its activation. The first cleavage step produces the opsonin fragment C3b that covalently (through a thioester bond) attaches to pathogens and other surfaces, tagging them for recognition and elimination by phagocytic cells, and the fragment C3a that contributes to inflammatory response and phagocytosis.…”

“…Complement activation occurs through three different pathways: the classical, alternative, and lectin pathways. All three pathways converge at complement component C3 . Complement C3 undergoes a series of cleavage steps that activate, inactivate, and redirect its activation.…”