The Complement System

Question 1

What is the complement system?

Answer 1

A collection of circulating and cell membrane proteins that play important roles in host defense against microbes and in antibody-mediated tissue injury

Question 2

How is the complement system activated?

Answer 2

• Activated by microbes in the absence of antibody as part of the innate response to infection
• Activated by antibodies attached to microbes as part of adaptive immunity

Question 3

How is the activation of the complement system achieved?

Answer 3

-Involves sequential proteolytic cleavage of the proteins, leading to the generation of effector molecules that participate in the elimination of microbes in various ways

Question 4

Name the 3 major pathways for complement activation and how do they differ?

Answer 4

1. Alternative Pathway
2. Classical Pathway
3. Lectin Pathway

The Alternative and Lectin pathways are initiated by microbes in the absence of antibodies while the classical pathway is initiated by isotypes of antibodies attached to antibodies.

Question 5

Name the most abundant complement protein

Answer 5

C3. Plays a central role in all 3 pathways

Question 6

What is the fate of C3?

Answer 6

C3 is spontaneously hydrolyzed in the plasma at a low level, but its products are unstable, rapidly broken down and lost

Question 7

What triggers the alternative pathway?

Answer 7

1. C3b, a breakdown product of C3 hydrolysis, is deposited on the surface of a microbe
2. C3b forms a stable covalent bond with microbial proteins or polysaccharides and is thus protected from further degradation
3. C3b binds to another protein called Factor B, which is broken down by a plasma protease to generate the Bb fragment. Bb remains attached to C3b, and the C3bBb complex enzymaticalled breaks down more C3, thus functioning as C3 convertase.
4. C3bBb molecules bind to additional C3b molecules and the C3bB3b complex functions as a convertase to breakdown the complement protein C5 and initiate the last steps of complement activation.

Question 8

What is the function of C3b?

Answer 8

It binds covalently to the surface of target cell. It is not only acts as a protease to catalyze subsequent steps in the complement cascade, but it is also recognized by specific receptor on macrophages and neutrophils that enhance the ability of these cells to phagocytose the target cell.

Question 9

What is the function of the smaller fragment of C3, C3a?

Answer 9

Promotes inflammatory response by encouraging white blood cells to migrate into the site of infection

Question 10

What triggers the classical pathway of complement activation?

Answer 10

Triggered when IgM or IgG (IgG1, IgG2, IgG3) antibodies bind to antigens on the surface of microbes.

Question 11

What are the steps for classical pathway activation of complement system?

Answer 11

1. IgM or IgG binds to antigens on Microbe
2. Fc region of antibody bind to C1 complement protein. C1 is composed of 3 subcomponents, C1q, C1r, and C1s.
3. C1 becomes enzymatically active resulting in the binding and sequential cleavage of proteins C4 and C2.