The complement system is a biochemical cascade that helps, or “complements”, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system.biochemical cascade pathogensimmune systeminnate immune systemadaptive immune system

The complement system consists of a number of small proteins found in the blood, generally synthesized by the liver, and normally circulating as inactive precursors (pro-proteins).pro-proteins When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages.proteasescytokines The end-result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex.membrane attack complex Over 25 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. These proteins are synthesized mainly in the liver, and they account for about 5% of the globulin fraction of blood serum.serumliverglobulin

Functions of the Complement The following are the basic functions of the complement Opsonization - enhancing phagocytosis of antigens Chemotaxis - attracting macrophages and neutrophils Lysis - rupturing membranes of foreign cells Clumping of antigen-bearing agents Altering the molecular structure of viruses

Consequences of Complement Activation: 1. Cytolysis: Due to the formation of a membrane attack complex (MAC) which produces lesions in microbial membranes. 2. Inflammation: Complement components (C3a) trigger the release of histamine, which increases vascular permeability. 3. Opsonization: Complement components (C3b) bind to microbial surface and promote phagocytosis. 4. Inactivation of Complement: Regulatory proteins limit damage to host cells that may be caused by complement.

Three biochemical pathways activate the complement system:biochemical pathways the classical complement pathway,classical complement pathway the alternative complement pathway,alternative complement pathway and the mannose-binding lectin pathwaymannose-binding lectin pathway

SUMMARY The complement system comprises a group of serum proteins, many of which exist in inactive forms. 1. Complement activation occurs by the classical, alternative, or lectin pathways, each of which is initiated differently. 2.The three pathways converge in a common sequence of events that leads to generation of a molecular complex that causes cell lysis. 3. The classical pathway is initiated by antibody binding to a cell target; reactions of IgM and certain IgG subclasses activate this pathway. 4. Activation of the alternative and lectin pathways is antibody- independent. These pathways are initiated by reaction of complement proteins with surface molecules of microorganisms. 5. In addition to its key role in cell lysis, the complement system mediates opsonization of bacteria, activation of inflammation, and clearance of immune complexes. 6. Interactions of complement proteins and protein fragments with receptors on cells of the immune system control both innate and acquired immune responses. 7. Because of its ability to damage the host organism, the complement system requires complex passive and active regulatory mechanisms. 8. Clinical consequences of inherited complement deficiencies range from increases in susceptibility to infection to tissue damage caused by immune complexes.

Classical Complement Pathway is Triggered by Antibodies Binding to Foreign Cells

Classical and Alternative Complement Pathways Cause Inflammation, Opsonization, and Cytolysis

Cytolysis Caused by Membrane Attack Complex

Functions of Complement

Complement-Mediated Lysis of E. coli Alive Killed

Role in disease Main article: Complement deficiencyComplement deficiency It is thought that the complement system might play a role in many diseases with an immune component, such as Barraquer-Simons Syndrome, asthma, lupus erythematosus, glomerulonephritis, various forms of arthritis, autoimmune heart disease, multiple sclerosis, inflammatory bowel disease, and ischemia-reperfusion injuries. The complement system is also becoming increasingly implicated in diseases of the central nervous system such as Alzheimer's disease and other neurodegenerative conditions. Barraquer-Simons Syndromeasthmalupus erythematosus glomerulonephritisarthritisautoimmune heart diseasemultiple sclerosisAlzheimer's disease Deficiencies of the terminal pathway predispose to both autoimmune disease and infections (particularly Neisseria meningitis, due to the role that the C56789 complex plays in attacking Gram-negative bacteria). autoimmune diseaseinfectionsNeisseria meningitisGram-negative, an autoimmune condition resulting from reduced regulation of the complement pathway. Mutations in the MAC components of complement--esp. C8-- are often implicated in recurrent Nessaria infection.