Complement Complement.Serum proteins,found in the blood,along with cells of the immune system work together to eliminate foreign cells.Once activated,the complement system can bring about a variety of responses.This complement system consists of three separate Along with this triggers,there are also two sets of mechanisms.Both of these mechanisms, classical pathway and alternative or properdin pathway,make MAC (Membrane Attack Complex),which can lyse and destroy the cell. Complement(Heat-Labile Substance) Destroy No Heat, by Heat but nent Cell Lysis No Cell Lysis Complement,antibodies,and cellular antigens are required for cell lysis C1, C4,C2,C3 C5,C6,C7,C8,C9 Discharge of ysosom al enzyme C3a Histamine release _Inflammation C4a edema
Complement Complement. Serum proteins, found in the blood, along with cells of the immune system work together to eliminate foreign cells. Once activated, the complement system can bring about a variety of responses. This complement system consists of three separate activation triggers: (1) Ab binding to a cell surface, (2) formation of immune complexes, and (3) a carbohydrate component of a microbe's cell membrane. Along with this triggers, there are also two sets of mechanisms. Both of these mechanisms, classical pathway and alternative or properdin pathway, make MAC (Membrane Attack Complex), which can lyse and destroy the cell
-C1q410,0001w -C1s87.000Hw 190.000Hw CI recognition complex Tw laG molecules Or one IgM molecule binding to antibody. CIs become an active enzyme(esterase) substrate. Structure of the Cl Molecule.The Cl protein is composed of three proteins:Clq,which binds to the Fc portion of the Ab molecule;Cls,which can enzymatically cleave the next complement component,C4:and CIr,which acts as a bridge connecting Clq to Cls
Structure of the C1 Molecule. The C1 protein is composed of three proteins: C1q, which binds to the Fc portion of the Ab molecule; C1s, which can enzymatically cleave the next complement component, C4; and C1r, which acts as a bridge connecting C1q to C1s
nitial r of the classical ent path W9wg999W9ggW99¥¥yygW9W99g99 C4b Ca C3b C3h Mg C2b C3a Opsonizing activity ct 80.00 3 C1 esterase c2 115,000 C1s -Enzymatic phase- erminal reactions of the classical complement pathwa MAC 8163.68079.000Mw -Enzymatic phase十 Attack phase-
Proteolytie Cleavage of C4.C3.and C5 Molecules c国 C3 Convertase 462h3 Y Chain o Chain Chain a Chain B Chain anaphylatoxic activity opsonization activity Membrane Attack Complex (MAC) 1A C9 (10 to 18 molecules) membrane membrane pore10 Transmembrane Channel formed by C9 polymers Classical Complement Pathway. The classical complement pathway requires the presence of antibodies,either as immunoglobulin (IgG or IgM)bound to cell surface Ag or as an Ag-Ab immune complex The serum proteinCl binds to the antibody,which in turn results in activation of C4,C2,and C3,and leads to the formation of C5,C6,C7,C8 and C9.This eventually
Classical Complement Pathway. The classical complement pathway requires the presence of antibodies, either as immunoglobulin (IgG or IgM) bound to cell surface Ag or as an Ag-Ab immune complex. The serum protein C1 binds to the antibody, which in turn results in activation of C4, C2, and C3, and leads to the formation of C5, C6, C7, C8 and C9. This eventually
leads to the formation of the C5-C9 membrane attack complex (MAC),which lyses and destroys the cell. Found in the classical complement pathway are three phases or stages.These are (1) a recognition phase. during which the complement system becomes activated:(2)an enzymtic phase,which is characterized by amplification of complement activation: and (3)an attack phase,during which cell destruction actually occurs. Recognition Phase.The recognition phase initiates the classical complement pathway when the inactive Cl serum protein interacts with the Fc portion of either cell-bound Ig (IgG or IgM)or an immune complex.Even though only one IgM-bound molecule is necessary to fix the Cl complex,two mole ecules of IgG bound in close proximity are required for activation to occur.This Cl recognition complex requires calcium to form the inactive unit,Cl,which consist of one molecule of Clq and two molecules of each of Clr and Cls.When the Ab is bound,Clq connects with the Ab receptor sites located on the Fc portions of two adjacent Ab molecules.These sites are exposed when the Ab binds to the Ag.After binding to the site Clq undergoes a conformational change,which causes Clr to activate itself by limited self-cleavage.CIr now sees Cls as its substrate and activation of Cls gives rise to its ability to cleave the next two complement proteins,C4 and C2. Enzymatic Phase Activation of C4 and C2 involves the cleavage of a specific peptide deee ren the disociation or ents, C4a and osure of a binding site in the larger fragment The C4b peptid binds to the cell membrane,while C2b attaches itself to the C4b fragment.This C4b2 complex is enzymatically active,requires magnesium ions,and is called C3 convertase since it can bind and cleave the next inactive complement component in the sequence, ctivation of c3 initiatess the ronerati n C3 is cleaved cell membrane and C4b2b complex,while the smaller fragment,C3a,is released to the body fluids.C4b2b3b is termed C5 convertase (or C3/C5 convertase),and its newly created catalytic site now accommodates C5.the next component in the sequence. Attack Phase The attack phase begins when C5 convertase (C3/C5)cleaves C5 into tw products, d c5b. s released when forme an.binding of Csh lends to the unoito roe ced C7 on the molecule,producing a stable complex,C5b67,which attaches to the membrane surface and enables C8 to bind.C8,in turn,binds several C9 molecules.This stable complex is called C5b6789,or MAC. The membrane attack complex (MAC)can produce a lesion in the plasma membrane causing cell lysis
leads to the formation of the C5-C9 membrane attack complex (MAC), which lyses and destroys the cell. Found in the classical complement pathway are three phases or stages. These are (1) a recognition phase, during which the complement system becomes activated; (2) an enzymatic phase, which is characterized by amplification of complement activation; and (3) an attack phase, during which cell destruction actually occurs. Recognition Phase. The recognition phase initiates the classical complement pathway when the inactive C1 serum protein interacts with the Fc portion of either cell-bound Ig (IgG or IgM) or an immune complex. Even though only one IgM-bound molecule is necessary to fix the C1 complex, two molecules of IgG bound in close proximity are required for activation to occur. This C1 recognition complex requires calcium to form the inactive unit, C1, which consist of one molecule of C1q and two molecules of each of C1r and C1s. When the Ab is bound, C1q connects with the Ab receptor sites located on the Fc portions of two adjacent Ab molecules. These sites are exposed when the Ab binds to the Ag. After binding to the sites, C1q undergoes a conformational change, which causes C1r to activate itself by limited self-cleavage. C1r now sees C1s as its substrate and activation of C1s gives rise to its ability to cleave the next two complement proteins, C4 and C2. Enzymatic Phase Activation of C4 and C2 involves the cleavage of a specific peptide bond in each molecule, resulting in the dissociation of peptide fragments, C4a and C2a, and the exposure of a binding site in the larger fragment, C4b2b. The C4b peptide binds to the cell membrane, while C2b attaches itself to the C4b fragment. This C4b2b complex is enzymatically active, requires magnesium ions, and is called C3 convertase since it can bind and cleave the next inactive complement component in the sequence, C3. Activation of C3 initiates the generation of a second convertase enzyme. This occurs when C3 is cleaved into C3a and C3b. The larger C3b fragment attaches to both the cell membrane and C4b2b complex, while the smaller fragment, C3a, is released to the body fluids. C4b2b3b is termed C5 convertase (or C3/C5 convertase), and its newly created catalytic site now accommodates C5, the next component in the sequence. Attack Phase The attack phase begins when C5 convertase (C3/C5) cleaves C5 into two products, C5a and C5b. C5a is released when formed and C5b attaches to the cell membrane. The binding of C5b leads to the uncovering of a binding site for C6 and C7 on the molecule, producing a stable complex, C5b67, which attaches to the membrane surface and enables C8 to bind. C8, in turn, binds several C9 molecules. This stable complex is called C5b6789, or MAC. The membrane attack complex (MAC) can produce a lesion in the plasma membrane causing cell lysis