complement

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complement

 [kom´plĕ-ment]
a term originally used to refer to the heat-labile factor in serum that causes immune cytolysis (lysis of antibody-coated cells). It is now used to refer to the entire functionally related system comprising at least 20 distinct serum proteins, their cellular receptors, and related regulatory proteins; this system is the effector not only of immune cytolysis but also of other biologic functions including anaphylaxis, phagocytosis, opsonization, and hemolysis.

Complement activation occurs by two different sequences, the classical pathway and the alternative pathway. All of the “components of complement,” designated C1 through C9 (C1 being composed of three distinct proteins, C1q, C1r, and C1s), participate in the classical pathway; the alternative pathway lacks components C1, C2, and C4 but adds factor b, factor d, and properdin. Regulatory proteins include factor h, factor i, clusterin, C3 nephritic factor, decay accelerating factor, homologous restriction factor, C1 inhibitor, C4 binding protein, membrane cofactor protein, protectin, and vitronectin.

The classical pathway is primarily activated by the binding of C1 to antigen-antibody complexes containing the immunoglobulins IgM or IgG. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classical pathway triggers an enzymatic cascade involving C1, C4, C2, and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B and D and properdin. Both pathways result in cleavage of C5 and formation of the membrane attack complex, which in its final state creates a pore in the cell wall and causes cell lysis. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case-letter suffixes, e.g., C3a.
 Complement activation. Activation of the classical and alternative pathways leads to a common terminal pathway from C5 to C9. These complement components form the final membrane attack complex (MAC). Other intermediate complexes and fragments are also biologically active: opsonins facilitate phagocytosis, anaphylatoxins act on mast cells and mediate a release of histamine which acts on blood vessels, and chemotactic fragments and intermediate complexes attract leukocytes to the site of inflammation. Redrawn from Damjanov, 2000.
complement fixation the combining of complement with the antigen-antibody complex, rendering the complement inactive, or fixed. Its presence or absence as free, active complement can be shown by adding sensitized blood cells to the mixture. If free complement is present, hemolysis occurs; if not, no hemolysis is observed. This reaction is the basis of many serologic tests for infection, including the wassermann test for syphilis, and reactions for gonococcus infection, glanders, typhoid fever, tuberculosis, and amebiasis. Called also Bordet-Gengou phenomenon. See also immunity.
complement fixation tests tests that use antigen-antibody reaction and result in hemolysis to determine the presence of various organisms in the blood; see also complement fixation.

com·ple·ment

(kom'plĕ-ment), Avoid the misspelling compliment.
Ehrlich's term for the thermolabile substance, normally present in serum, that is destructive to certain bacteria and other cells sensitized by a specific complement-fixing antibody. Complement is a group of at least 20 distinct serum proteins, the activity of which is affected by a series of interactions resulting in enzymatic cleavages; it can follow one or the other of at least two pathways. In the case of immune hemolysis (classical pathway), the complex comprises nine components (designated C1 through C9) that react in a definite sequence and the activation of which is usually effected by the antigen-antibody complex; only the first seven components are involved in chemotaxis, and only the first four are involved in immune adherence or phagocytosis or are fixed by conglutinins. An alternative pathway (see properdin system) may be activated by factors other than antigen-antibody complexes, such as repeating polysaccharides or bacterial cell wall components, and involves components other than C1, C4, and C2 in the activation of C3. The terminal complement components form a membrane attack complex that leads to cytolysis of the target cell.
See also: component of complement.
[L. complementum, that which completes, fr. com-pleo, to fill up]

complement

/com·ple·ment/ (kom´plĕ-ment) a heat-labile cascade system of at least 20 serum glycoproteins that interact to provide many of the effector functions of humoral immunity and inflammation, including vasodilation and increase of vascular permeability, facilitation of phagocyte activity, and lysis of certain foreign cells. It can be activated via either the classical or alternative complement pathways (qq.v.).
Enlarge picture
Schematic representation of the classical complement pathway. The pathway is initiated by binding of two antibody molecules to a multivalent antigen, followed by binding of complement protein C1q, and then by binding of two molecules each of C1r and C1s to C1q to form the active complex C1 (A). C4 binds to the C1q portion of C1 (B), and the esterolytic site on C1s activates C4 by splitting off C4b, which binds the antigen-antibody complex or the nearby cell surface (C). The same site on C1s then cleaves and activates C2 which has bound to C4b, yielding a C4b2a complex (C3 convertase) (D). The C3 convertase binds C3 and cleaves it to the active form C3b (E), which binds to the cell surface and to the C3 convertase to form a C4b2a3b complex (C5 convertase) (F). The late phase of complement activation begins when the C5 convertase cleaves C5 to the active form C5b (G). C5b remains at the cell surface and binds first C6 then C7 (H); the latter is hydrophobic and inserts into the plasma membrane (I), where it is joined by C8 (J). As many as 19 molecules of C9 then polymerize at C5678 to form pores in the plasma membrane (K); this final complex is called the membrane attack complex (MAC). Entry of water through the pores into the cell causes osmotic swelling and cell rupture (L).

complement

(kŏm′plə-mənt)
n.
Immunology A complex system of proteins found in normal blood plasma that combines with antibodies to destroy pathogenic bacteria and other foreign cells. Also called alexin.

complement (C)

[kom′pləmənt]
Etymology: L, complementum, that which completes
a system of at least 20 complex enzymatic serum proteins. In an antigen-antibody reaction, activation of complement causes cell lysis. Complement is also involved in other physiological reactions, including inflammation, anaphylaxis, and phagocytosis. See also antibody, antigen, antigen-antibody reaction, immune gamma globulin.

complement

Immunology
adjective Pertaining to the complement system.
 
noun
(1) Any protein of the complement system.
(2) Complement system—first used for a heat-labile factor in serum that caused immune cytolysis of antibody coated cells, the complement system now refers to the entire functionally-related system, comprising ± 25 distinct serum proteins that mediate the nonspecific inflammatory response to various antigens through a complex sequence of enzymatic cleavages. Complement is thus the effector not only of immune cytolysis but also of other biologic functions; it is activated by 2 routes, the classic and alternative pathways.

Medspeak
noun A set of something.

Complement reference ranges
Ÿ Total Complement—40–100 Units.
Ÿ C1:
   – C1q—70 µg/mL;
   – C1r—34 µg/mL;
   – C1s—31 µg/mL.
Ÿ C2—25 µg/mL.
Ÿ C3—1600 µg/mL.
Ÿ C4—600 µg/mL.
Ÿ C5—85 µg/mL.
Ÿ C6—75 µg/mL.
Ÿ C7—55 µg/mL.
Ÿ C8—55 µg/mL. 
Ÿ C9—60 µg/mL.
Ÿ Factor B—200 µg/mL.
Ÿ Factor D—1 µg/mL.

complement

Immunology adjective Pertaining to the complement system noun
1. Any protein of the complement system.
2. Complement system The term was first used for a heat labile factor in serum that caused immune cytolysis of antibody coated cells; it now refers to the entire functionally related system comprising ± 25 distinct serum proteins, which mediate the nonspecific inflammatory response to various antigens through a complex sequence of enzymatic cleavages; complement is thus the effector not only of immune cytolysis but also of other biologic functions; it is activated by 2 routes, the classic and alternative pathways. See Alternative pathway, Classic pathway, Complement activation Medtalk noun A set of something. See Chromosome complement.

com·ple·ment

(kom'plĕ-mĕnt)
The thermolabile substance, normally present in serum, which is destructive to certain bacteria and other cells sensitized by a specific complement-fixing antibody. Complement is a group of at least 20 distinct serum proteins, the activity of which is affected by a series of interactions resulting in enzymatic cleavages and which can follow one or the other of at least two pathways. In the case of immune hemolysis (classical pathway), the complex comprises nine components (designated C1-C9) that react in a definite sequence and the activation of which is usually effected by the antigen-antibody complex; only the first seven components are involved in chemotaxis, and only the first four are involved in immune adherence or phagocytosis or are fixed by conglutinins. An alternative pathway (see properdin system)may be activated by factors other than antigen-antibody complexes and involves components other than C1, C4, and C2 in the activation of C3.
See also: component of complement
[L. complementum, that which completes, fr. com-pleo, to fill up]

complement

A collection of about 20 serum proteins involved in the immune system process by which the action of antibodies against the invading agent (the ANTIGEN) is completed. Complement combines with antigen-antibody complexes to bring about the breakdown of the antigen-bearing cell or molecule. Some of the serum proteins form enzyme-activated cascades to produce molecules involved in INFLAMMATION, PHAGOCYTOSIS and cell rupture.

complement

the protein components of blood serum that can bind to antigen/antibody groups already formed on the surface of cells, thus enhancing destruction of the foreign body by PHAGOCYTES.

Complement

One of several proteins in the blood that acts with other proteins to assist in killing bacteria.
Mentioned in: Meningococcemia

complement

group (∼20) of serum proteins sequentially activated by inflammation or infection; and essential to normal healing

com·ple·ment

(kom'plĕ-mĕnt)
Thermolabile substance, normally present in serum, which is destructive to bacteria and other cells sensitized by a specific complement-fixing antibody.
[L. complementum, that which completes, fr. com-pleo, to fill up]

complement (kom´pləment),

n one of 11 complex, enzymatic serum proteins. In an antigen-antibody reaction, complement causes lysis. Complement is also involved in anaphylaxis and phagocytosis.
complement fixation,
n an immunologic reaction in which an antigen combines with an antibody and its complement, causing the complement factor to become inactive, or “fixed.”
complement-fixation test (C-F test),
n a serologic test in which complement fixation is detected, indicating the presence of a particular antigen. The Wassermann test for syphilis is a C-F test, used to detect amebiasis, Rocky Mountain spotted fever, try-panosomiasis, and typhus.

complement

a complex series of enzymatic proteins occurring in normal serum that are triggered in a cascade manner by, and combine with, the antibody-antigen complexes, producing lysis when the antigen is an intact cell. Complement comprises 25 to 30 discrete proteins, labeled numerically as C1 to C9, and by letters, i.e. B, D, P, etc., and with C1 being divided into subcomponents C1q, C1r and C1s. Components C3 and C5 are involved in the generation of anaphylatoxin and in the promotion of leukocyte chemotaxis, the result of these two activities being the inflammatory response. C1 and C4 are involved in the neutralization of viruses. The components also combine in various sequences to participate in other biological activities, including antibody-mediated immune lysis, phagocytosis, opsonization and anaphylaxis. The complement system is known to be activated by the immunoglobulins IgM and IgG.

alternate complement pathway, alternative complement pathway
the sequence in which complement components C3 and C5 to C9 are activated without participation by C1, C2 and C4 or the presence of an antibody-antigen complex.
complement cascade
the sequence of reactions, each being the catalyst for the next, that leads to the terminal complement pathway and cell lysis. There are two pathways for activation of C3, the 'classical' (below) and the 'alternate' (above).
classical complement pathway
the one in which all of the complement components C1 to C9 participate and is triggered by antibody-antigen complexes.
complement deficiency
various complement components may be deficient without serious effects on the host. C3 deficiency is most severe and occurs in humans, Brittany spaniels and Finnish-Landrace lambs. Increased susceptibility to infections results.
complement fixation tests
utilize antibody-antigen reaction and result in hemolysis to determine the presence of various organisms in the blood. Involves two stages. In the first, also referred to as the test system, antigen is mixed usually with serial dilutions of a test serum in the presence of complement. If the serum contains antibody, i.e. is positive, an antibody-antigen complex is formed which also binds (fixes) complement. In the second stage, also called the indicator system, sheep red blood cells coated with specific, usually rabbit anti-sheep red blood cell antibody are added. The red blood cells are said to be sensitized. If antibody was not present in stage 1, then the free complement lyses the sensitized sheep red blood cells. The basis of many serological tests including those for glanders, tuberculosis and contagious bovine pleuropneumonia. Called also Bordet-Gengou phenomenon. See also immunity.
complement regulatory proteins
a set of at least seven proteins that are present in plasma (C1 INH, C4b-binding protein, factor H and factor I) or present in cell membranes (decay-accelerating factor [DAF], membrane cofactor protein [MCP] and homologous restriction factor [HHF]) that modulate the complement proteins and protect 'innocent' bystander cells and tissues from complement damage.
terminal complement pathway
the final stages of complement activation in which C5, C6, C7, C8 and C9 are activated; common to both the alternate and classical pathways.
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