Biological Functions of Complement Proteins
المؤلف:
Mary Louise Turgeon
المصدر:
Immunology & Serology in Laboratory Medicine
الجزء والصفحة:
5th E, P83-85
2025-07-05
554
The biological functions of the complement system fall into the following two general categories:
1. Cell lysis by the membrane attack complex (MAC)
2. Biological effects of proteolytic fragments of complement
The first category is the situation in which the MAC leads to osmotic lysis of a cell. The second category encompasses other effects of complement in immunity and inflammation that are mediated by the proteolytic fragments generated during complement activation. These fragments may remain bound to the same cell surfaces at which complement has been activated or may be released into the blood or extracellular fluid. In either situation, active fragments mediate their effects by binding to specific receptors expressed on various types of cells, including phagocytic leukocytes and the endothelium (Table 1).
Table1. Selected Complement Components and Functions
In contrast, the absence of an integral component of the classic, alternative, or terminal lytic pathways can lead to decreased complement activation and a lack of complement - mediated biological functions.
Alterations in Complement Levels
The complement system can cause significant tissue damage in response to abnormal stimuli. Biological effects of complement activation can occur as a reaction to persistent infection or an autoantibody response to self-antigens. In these infectious or autoimmune conditions, the inflammatory or lytic effects of complement may contribute significantly to the pathology of the disease.
Complement activation is also associated with intravascular thrombosis, which leads to ischemic injury to tissues. Complement levels may be abnormal in certain disease states (e.g., rheumatoid arthritis, systemic lupus erythematosus [SLE]) and in some genetic disorders.
Elevated Complement Levels
The complement level can be elevated in many inflammatory conditions. Increased complement levels are often associated with inflammatory conditions, trauma, or acute illness such as myocardial infarction because separate complement components (e.g., C3) are acute-phase proteins. However, these elevations are common and nonspecific. Therefore, increased levels are of limited clinical significance.
Decreased Complement Levels
Low levels of complement suggest one of the following bio logical effects:
• Complement has been excessively activated recently.
• Complement is currently being consumed.
• A single complement component is absent because of a genetic defect.
Specific component deficiencies are associated with a variety of disorders (Table 2). Deficiencies of complement account for a small percentage of primary immunodeficiencies (<2%) , but depression of complement levels frequently coexists with SLE and other disorders associated with an immunopathologic process (Box 1).
Table2. Complement Deficiency in Human Beings
Box1. Diseases Associated With Hypocomplementemia
Deficiencies in any of the protein components of complement are usually caused by a genetic defect that leads to abnormal patterns of complement activation. If regulatory components are absent, excess activation may occur at the wrong time or at the wrong site. The potential consequences of increased activation are excess inflammation and cell lysis and consumption of complement components.
Hypocomplementemia can result from the complexing of IgG or IgM antibodies capable of activating complement. Depressed values of complement are associated with diseases that give rise to circulating immune complexes. Because of the rapid normal turnover of the complement proteins—within 1 or 2 days of the cessation of complement activation by immune complexes—complement levels return to normal rapidly.
The following three types of complement deficiency can cause increased susceptibility to pyogenic infections:
1. Deficiency of the opsonic activities of complement
2. Any deficiency that compromises the lytic activity of complement
3. Deficient function of the mannose-binding lectin pathway
Increased susceptibility to pyogenic bacteria (e.g., Haemophilus influenzae, Streptococcus pneumoniae) occurs in patients with defects of antibody production, complement proteins of the classic pathway, or phagocyte function. The sole clinical association between inherited deficiency of MAC components and infection is with neisserial infection, particularly Neisseria meningitidis. Low levels of mannose-binding lectin in young children with recurrent infections suggest that the mannose binding lectin pathway is important during the interval between the loss of passively acquired maternal antibody and the acquisition of a mature immunologic repertoire of antigen exposure.
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