Changes

==Complement Fixation==

==Complement Fixation==

Complement gets its name because it complements the function of antibody. Complement belongs to a group of plasma systems termed the triggered enzyme cascades, which also include the blood clotting system and the kinin cascade. They are all effector mechanisms that can produce a rapid and amplified response to a trigger stimulus. Such mechanisms have adaptive value if invoked in appropriate circumstances but may be harmful if triggered inappropriately. They are complex systems both in their reaction pathways and in their control mechanisms. There are more than 20 different proteins (most are enzymes or pro-enzymes) in the complement cascades. It pre-dates the immune system evolutionarily, and has evolved as one of the main innate protective mechanisms of invertebrates. Complement works largely by triggering acute inflammation and by promoting phagocytosis by macrophages and neutrophils.  

 

* Complement is so called because it complements the function of antibody.  

* Complement is a '''triggered enzyme cascade'''.

** These are a group of plasma systems.

** Other examples include:

*** The clotting system.

*** the kinin cascade.  

** The triggered enzyme cascades are effector mechanisms that can produce a rapid and amplified response to a trigger stimulus.

*** Have adaptive value if appropriately invoked.

*** May be harmful if triggered inappropriately.

They are complex systems both in their reaction pathways and in their control mechanisms. There are more than 20 different proteins (most are enzymes or pro-enzymes) in the complement cascades. It pre-dates the immune system evolutionarily, and has evolved as one of the main innate protective mechanisms of invertebrates. Complement works largely by triggering acute inflammation and by promoting phagocytosis by macrophages and neutrophils.  

The central event in complement activation is the splitting (by hydrolysis) of the major complement protein - C3; this is a large 2-chain molecule and hydrolysis results in the removal of a small peptide – C3a, leaving the highly reactive but very short-lived molecule - C3b. This happens, spontaneously and slowly, in plasma and the reactive C3b in rapidly inactivated. However, bacterial cell surfaces protect the reactive C3b from this rapid inactivation (it is still inactivated but more slowly) and this is the basis of the archaic complement system that is now termed the alternative pathway of complement activation. Subsequently the immune system has optimized complement activation via antibody - antigen complexes; this is now termed the classical pathway of complement activation. The difference between the two pathways only involves the mechanisms of C3 breakdown to C3b. Once C3 is hydrolysed, the later terminal pathway is the same and is often called the membrane attack complex or MAC and involves the binding of C5-C9. The complex sequence of events in both the alternative and classical pathway of complement activation (or complement fixation) is shown in Figure 1.

The central event in complement activation is the splitting (by hydrolysis) of the major complement protein - C3; this is a large 2-chain molecule and hydrolysis results in the removal of a small peptide – C3a, leaving the highly reactive but very short-lived molecule - C3b. This happens, spontaneously and slowly, in plasma and the reactive C3b in rapidly inactivated. However, bacterial cell surfaces protect the reactive C3b from this rapid inactivation (it is still inactivated but more slowly) and this is the basis of the archaic complement system that is now termed the alternative pathway of complement activation. Subsequently the immune system has optimized complement activation via antibody - antigen complexes; this is now termed the classical pathway of complement activation. The difference between the two pathways only involves the mechanisms of C3 breakdown to C3b. Once C3 is hydrolysed, the later terminal pathway is the same and is often called the membrane attack complex or MAC and involves the binding of C5-C9. The complex sequence of events in both the alternative and classical pathway of complement activation (or complement fixation) is shown in Figure 1.