complement pathways

Question 1

Describe the classical pathway

Answer 1

• Gets initiated/activated when antibodies bind to the antigen of a pathogen.
• Once that happens complement proteins composed of C1Q binds to Fc portion, C1S, & C1R binds to antibodies then forms a complement protein complex known as the C4b2Aa Complex (C3 convertase, an enzyme)

Question 2

Lectin pathway (similar to classical pathway but involve different types of proteins in the activation of the C4b2a complexes)

Answer 2

• Initiated/activated when proteins bind to carbohydrates on the pathogen
  
  • For example, the protein called Filcolin binds to oligosaccharides of a pathogen (bacteria)
  • Filcolin also has other proteins bound to it, MASP-1 & MASP-2
    Another type of protein is the Mannose binding lectin MBL binds to mannose parts of pathogen
  • Mannose binding lectin also comprises of other proteins the MASP-1 & 2 (Mannose associated proteins)
• Filcolin and Mannose binding lectin both form a complement protein complex with other mannose associated proteins. The same as a classical one (C4b2a, also known as C3 convertase)

Question 3

The alternative pathway becomes activated when?

Answer 3

The classical pathway and lectin pathway forms the c4b2a complex or C3 convertase. Once they activate C3b

• C3b then binds on the surface of the pathogen
• The alternative pathway will then form another type of C3 convertase different from the ones formed in the lectin and classical pathways, this one is called C3Bb complex
• The alternative pathway can also form another type of C3 convertase this time with a protein called properin. This complex is known by C3bBb complex as well
• The alternative pathway essentially enhances the classical & lectin pathway or the other way around

Question 4

What does the C4b2a complex or C3 convertase do?

Answer 4

• C3 convertase is on the surface of a pathogen, it essentially activates C3 protein.
• It splits the C3 to form C3b and C3a

Question 5

All of the pathways form what?

Answer 5

A C3 convertase and what it does is that it activates C3 which splits C3 into C3a and C3b

Question 6

What does C3a do?

Answer 6

Along with other complement proteins such as C5a (one of the most important complement proteins) will enhance inflammation.

• All of the proteins with complement A will do some form of inflammatory process
• C3a and C5a will stimulate Mast cells to secrete histamine which enhances inflammation
• Histamine enhances inflammation, increases vascular permeability which allows leukocytes to pass through more easily & also attracts leukocytes

Question 7

What does C3b do?

Answer 7

• Can form thioester bonds
• Initiates opsonization and forms the initiation of the formation of the membrane attack complex
• Many C3b’s and C3a’s
• The C3b’s can bind to pathogen surface through theoester bond, many C3b’s forming theoester bonds with the pathogen surface so it coats the pathogen (opsonization) which allows macrophage to easily engulf the pathogen once it has been coated
• A macrophage has 2 special receptors for complement proteins, a CR1 and C5a receptor, it cannot engulf a pathogen coated with C3b on its own, it needs the help of another complement protein called C5a
• When C5a binds to C5a receptor of macrophage this allows the macrophage bind to the C3b protein through CR1 receptors
  Then it can perform phagocytosis

Question 8

Initiates the terminal phase (membrane attack complex)

Answer 8

C5b

Question 9

What does C5b do?

Answer 9

It is an important protein because it initiates the terminal stage the membrane attack complex (MAC).
- C5b together with other complement proteins such as
C-6,7,8,9 will form the membrane attack complex on the pathogen
- The formation of the membrane attack complex on a pathogens surface membrane will cause the pathogen to lyse