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Community Series in the Role of Complement in Health and Disease, volume II
The complement system is a crucial mediator of the innate immune response, interacting with other innate mechanisms and with factors of acquired immunity. It contributes significantly to cell homeostasis, tissue development and repair, reproduction, and cross-talk with other endogenous cascades. Each of the three major complement activation pathways (Classical, CP; Alternative, AP and Lectin, LP) employs specific recognition molecules and initiating serine proteases. All of them converge into a common pathway, leading to the formation of the biologically highly active anaphylatoxin C5a and the C5b-9 membrane attack complex (MAC). The latter forms transmembrane channels which either induce “sub-lytic” activation of the cell or result in target cell lysis. Although the complement system was discovered in 1888, nowadays this system is still under intense investigation with ongoing advances being made in various aspects including its clinical significance and its involvement in the regulation of the immune response.
Therapeutic Modulation of the Complement System: Clinical Indications and Emerging Drug Leads
The complement system is a multi-tasking gatekeeper of innate immunity thatintricately interacts with other key defense systems, such as the endothelial barrier,contact activation and coagulation systems, in maintaining tissue immunosurveillanceand homeostasis. Its rapid and forceful activation in the bloodstream not onlyensures the effective containment of microbial infections through potent cytolyticmechanisms, but also alerts the adaptive immune compartment to ensure the mountingof a proper humoral immune response against foreign antigens. However, there isa lurking ‘dark side’ that can lead complement astray, fueling a self-perpetuatingvicious cycle of inflammation, exuberant immune ...
Current Challenges in Complement Diagnostics
The complement system is an important innate immune surveillance network that has a key role in protecting our bodies against pathogens and other threats. It is a highly complex system consisting of approximately 50 soluble and cell surface-bound proteins that interact to eliminate danger signals. These signals include factors such as invading microorganisms, necrotic cells, and immune complexes. Furthermore, complement can link innate and adaptive immune responses by regulating T cell and B cell responses. The complement system is tightly regulated to avoid uncontrolled activation. Dysregulation of the complement system has been linked to numerous diseases, both rare and common. Uncontrolle...
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