Changes

===Classical Pathway===

===Classical Pathway===

[[Image:Complement Classical Pathway.png|thumb|right|250px|'''Classical pathway in detail''']]

[[Image:Complement Classical Pathway.png|thumb|right|250px|'''Classical pathway in detail''']]

<p>Triggered by the binding of antibody to antigen. Only [[IgM]] and certain [[IgG]] subclasses can activate complement this way.

<p>This pathway of the complement system is triggered by the binding of antibody to antigen. The only subclasses that can activate complement this way are the

#Immune complexes trigger complement activation by binding C1.

[[IgM]] and certain [[IgG]]. The first step of complement activation is the binding of C1 to two Fc regions of the antibodies (IgM is such a strong activator of complement as it contains '''five''' Fc regions, while IgG contains '''one'''). C1 is actually a complex of C1q, C1r and C1s. C1q looks like a bunch of 6 tulips with each "flower" consisting of a globular protein head and a collagen "stem". C1q is required to trigger the cascade because two of it is the globular heads which binds the two Fc regions. C1r and C1s then become activated when the C1q heads are antibody-bound. When they are activated they form the enzyme C1 esterase (serine protease).

 

#*C1 is a complex of:

#**C1q

 

#***Looks like a bunch of 6 tulips

 

#***Each "flower" consists 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

 

It is the C1 esterase which then first digests components C4 to C4a and C4b, and C2 to C2a and C2b. It is the C4b which first binds to the antigen, and then forms a complex with C2a to produce the active enzyme '''C3 convertase (classical pathway)'''. The binding of one C1q molecule produces one C1 esterase molecule that can then cause the binding of many hundreds of the C4b&macr;2a molecules, or the C3 convertase (classical pathway). The role of the convertase is to digest C3 into C3a and C3b. This part of the pathway is self-propagating as the production of C3b can now be amplified by the same mechanism as the alternative pathway (below).

 

#*C1r and C1s become activated when at least 2 C1q heads are antibody-bound (to FC region)

#**Form the enzyme C1 esterase (serine protease)

 

#C1 esterase first digests C4 to C4a and C4b and the C2 to C2a and C2b  

#*C4b binds to the antigen

 

#C4b then binds C2a

The main action of the C3b molecule is to form the C4b&macr;2a&macr;3b complex, or the '''C5 convertase (classical pathway)'''. The C5 convertase then activates C5 and initiates the [[#Membrane Attack Complex|membrane attack complex]] (MAC) as shown below. Other actions include the fragmentation of the C3b due to the actions of [[#Factors I and H|Factors I and H]] which forms C3bi, which provides an opsonin for [[Phagocytosis|phagocytosis]].

#*C4b and C2a complex to form the enzyme C2a&macr;4b (C3 convertase)

 

#C2a&macr;4b digests 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 causes the binding of many hundreds of C4b&macr;2b molecules

 

#*Forms C4b2&macr;a3b (C5 convertase)

Along with the actions of the fragments mentioned above, Ca fragments C3a, C4a and C5a, and Cb fragment C2b also form a chemotactic response. This brings [[Neutrophils|neutrophils]] to the area of complement activation through the process of [[Neutrohpils|extravasation]] through the increase in cell adhesion molecules on the endothelium and an increase in vascular permeability; and chemotaxis which is the direct cellular movement. The fragments can also cause [[Mast Cells|mast cell]] and [[Basophils|basophil]] degranulation. These therefore induce '''acute inflammation'''.

#*This activates C5 and initiates the [[#Membrane Attack Complex|membrane attack complex]] (MAC)

*Ca fragments C3a, C4a and C5a, and Cb fragment C2b

**Are chemotactic for [[Neutrophils|neutrophils]]  

**Increase vascular permeability and cell adhesion molecules

***Cause [[Mast Cells|mast cell]] and [[Basophils|basophil]] degranulation</p>

<p>Like the alternative pathway, another major effect of classical pathway activation is to produce iC3b due to the actions of [[#Factors I and H|Factors I and H]] which promotes phagocytosis and initiates inflammation</p>

===Alternative Pathway===

===Alternative Pathway===