Changes

===CLASSICAL PATHWAY ACTIVATION===

===CLASSICAL PATHWAY ACTIVATION===

There are two triggers for the classical pathway of complement activation, the first is  the binding of antibody to antigen. Only IgM and certain IgG subclasses can do. These antibodies can fix complement only after they bind antigen. Immune complexes trigger complement activation because they bind C1, which cross-links two antibody molecules. The C1 molecule is a complex of C1q, C1r and C1s. A C1q molecule looks like a bunch of 6 tulips – with each ‘flower’ consisting of a globular protein head and a collagen ‘stem’. At least two C1q globular heads must bind to antibody before the complement cascade is triggered. If this happens the inactive C1r and C1s molecules become activated to form an enzyme called C1 esterase. The first substrate of this enzyme is C4, which it digestes to form C4a and C4b. C4b binds to the antigen (e.g. a bacterial cell). C4b will then bind C2 – this is then, in turn, digested by C1 esterase to form C2a and C2b. All the Ca fragments (C2a, C3a, C4a, C5a) are chemotactic for neutrophils and are potent inducers of acute inflammation (they are termed the anaphylotoxins). The C4b2b complex is an enzyme (C ) that is capable of efficient digestion of C3 into C3a and C3b. The production of C3b can now be amplified by the same mechanism as the alternative pathway. The binding of one C1q molecule produces one C1 esterase molecule that then cause the binding of many hundreds of C molecules. The C3b molecule that is produced by the action of this enzyme can also bind to it, forming the complex enzyme C , which is the second enzyme capable of activating C5 and initiating the MAC. Like the alternative pathway, the major effects of classical pathway activation are to produce iC3b and hence it promotes phagocytosis and initiates inflammation.

* There are two triggers for the classical pathway of complement activation.

A second trigger of the Classical Pathway is the binding of soluble lectins (e.g. collectins) to pathogens. Lectins are proteins that bind carbohydrates, in this case carbohydrates that have a terminal mannose residue – they are called mannose-binding lectins and are secreted by the liver into plasma. This action of lectin binding to carbohydrate activates plasma-associated proteases called mannose-binding lectin associated proteases (MASPs), these act on C4 and C2 in the same way as C1 esterase.

*# '''The binding of antibody to antigen'''.  

*#* Only IgM and certain IgG subclasses can activate complement this way.

*#* Immune complexes trigger complement activation because they bind C1, which cross-links two antibody molecules. The C1 molecule is a complex of C1q, C1r and C1s. A C1q molecule looks like a bunch of 6 tulips – with each ‘flower’ consisting of a globular protein head and a collagen ‘stem’. At least two C1q globular heads must bind to antibody before the complement cascade is triggered. If this happens the inactive C1r and C1s molecules become activated to form an enzyme called C1 esterase. The first substrate of this enzyme is C4, which it digestes to form C4a and C4b. C4b binds to the antigen (e.g. a bacterial cell). C4b will then bind C2 – this is then, in turn, digested by C1 esterase to form C2a and C2b. All the Ca fragments (C2a, C3a, C4a, C5a) are chemotactic for neutrophils and are potent inducers of acute inflammation (they are termed the anaphylotoxins). The C4b2b complex is an enzyme (C ) that is capable of efficient digestion of C3 into C3a and C3b. The production of C3b can now be amplified by the same mechanism as the alternative pathway. The binding of one C1q molecule produces one C1 esterase molecule that then cause the binding of many hundreds of C molecules. The C3b molecule that is produced by the action of this enzyme can also bind to it, forming the complex enzyme C , which is the second enzyme capable of activating C5 and initiating the MAC. Like the alternative pathway, the major effects of classical pathway activation are to produce iC3b and hence it promotes phagocytosis and initiates inflammation.

*# '''The binding of soluble lectins to pathogens'''.

*#* E.g. collectins.

*#* Lectins are proteins that bind carbohydrates, in this case carbohydrates that have a terminal mannose residue – they are called mannose-binding lectins and are secreted by the liver into plasma. This action of lectin binding to carbohydrate activates plasma-associated proteases called mannose-binding lectin associated proteases (MASPs), these act on C4 and C2 in the same way as C1 esterase.

==MEMBRANE ATTACK COMPLEX==

==MEMBRANE ATTACK COMPLEX==