The Complement System

Question 1

The Complement System
Part I

Answer 1

The complement system is an essential component of innate immune system but also works downstream from adaptive immunity.
A major function of the complement system is to ensure rapid and effective antimicrobial defense: The complement system “asssits” or “complements” the activity of immune cells for the recognition and killing of pathogens.
The complement system also regulates a large array of immune and non-immune functions independently of infection.
Consists of at least 50 soluble effectors including structural proteins and enzymes C1 to C9, regulatory factors, and cytoplasmaic components. Soluble factors are mainly synthesized in the liver and released in the blood and lymphatic ciculatory systems.
The complement system also includes an array of cell surface receptors, many of which are name CR (Complement receptor).

Question 2

The Complement System
Part II

Answer 2

Complement system includes proteases produced as proenzymes (zymogens).
Activated ONLY when needed and its activation is tighly regulated. The absence of complement activation or its excessive activation can lead to pathological conditions.
There are three activation pathways of the complements system:
* Alternative Pathway
* Classical Pathway
* Lectin Pathway

Question 3

The Complement System
Part III

Answer 3

The three pathways are activated on biological surfaces
The mechanism of initiation of complement activation is different for each pathway
The three pathways are activated in a cascade-like fashion including amplification loop.
The three pathways converge toward the activation of the C3 and C5 convertases, which are enzymatic complexes leading to a common terminal pathway.
The three pathways share the same outcome: Lysis, opsonization, inflammation

Question 4

The Alternative Pathway

Answer 4

Spontaneous hydrolysis of a labile thioester bond in C3, which converts C3 to bioactive form [C3(H2O)Bb] int he fluid phase.
C3 convalent binding to microbial sruface following nucleophilic attact by amine or hydroxyl groups of proteins or carbohydrates on the microbial surface.
Factor D and Bb are serine proteases
C3 is the most abundant complement protein
Total complement: 3mg/ml plasma/serum
C3: 1.2 mg/ml plasma/serum

Question 5

Assembly of the MAC

Answer 5

Question 6

The Classical Pathway

Answer 6

IgG and IgA activate this pathway
C1r and C1s are enzymes

Question 7

All three pathways converge towars the formation of C3 and C5 convertase enzymatic complexes adn are magnified through this amplification loop

Answer 7