Lecture 4

Question 1

Name the 3 pathways of complement activation

Answer 1

Classical pathway

Lectin pathway

Alternative pathway

Question 2

What is the end product common to all 3 complement pathways?

Answer 2

Membrane attack complex (MAC).

Question 3

True or False: IgM is more efficient at initiating the classical pathway than IgG.

Answer 3

TRUE.

Because IgM is a pentamer, it does not require multiple antibodies to activate C1.

Question 4

Which complement protein is highest in concentration in the blood?

Answer 4

C3.

Question 5

What is the consequence of an unregulated complement system?

Answer 5

Death.

Question 6

What is the function of the membrane attack complex (MAC)?

Answer 6

Creates a pore in a cellular membrane, leading to cellular lysis.

Question 7

Name two mechanisms by which the complement system is regulated.

Answer 7

Substrate modulation

• a complement protein cannot be cleaved by a protease until it first binds to another protein. Prevents unnecesary cleavage.

Fragment binding

• complement molecules are cleaved into two parts. One part (b component) usually quickly covalently binds to a nearby surface. If it does not bind, it is quickly degraded. Limits enzyme cascades to site of infection.

Question 8

Which complement activation pathway is reliant on the adaptive immune system?

Answer 8

Classical pathway

Requires antibodies for C1 binding.

Question 9

True or False: The lectin and alternative pathways can be activated without the presence of antibodies.

Answer 9

TRUE

These pathways are considered as part of innate immunity.

Question 10

True or False: Mannose is commonly found in mammalian cells.

Answer 10

FALSE.

Mannose is typically found in bacteria, fungi, and other pathogenic microbes.

The presence of mannose on a microbe initiates the lectin pathway of complement activation.

Question 11

How many IgG molecules are required to fix complement?

Answer 11

At least 2, and they must be spaced closely together.

For this reason, approximately 10,000 IgG molecules must be bound to a cell before the complement cascade normally starts.

Question 12

Can C1 bind to free-floating antibodies in the blood stream?

Answer 12

No.

C1 can only bind to antibodies that have been bound to an antigen.

Question 13

What is the function of C3 convertase in the complement cascade?

Answer 13

Splits C3 into C3a and C3b.

C3a - causes increased vascular permeability and is chemotactic.

C3b - opsonization. Also binds with C3 convertase to create C5 convertase.

Question 14

Which complement molecule is responsible for opsonization of pathogens for later recognition by phagocytic cells?

Answer 14

C3b

Question 15

What is the general effect of complement activation on nearby vasculature?

Answer 15

Vasodilation

Increased vascular permeability

Question 16

What is the effect of calcium chelation on the complement system?

Answer 16

Inactivation.

C1 is a large complex of proteins held together by calcium. Chelating calcium effectively inactivates C1.

Question 17

What is the effect of Heparin on the complement system?

Answer 17

No effect.

Heparin is a thrombin antagonist. If added to serum, it will inactivate clotting factors, but will not affect complement.

Question 18

How might one inactivate complement in serum?

Answer 18

Calcium chelation (ex: EDTA)

-inactivates complement and clotting factors.

Heat to 56 degrees Celcius for 30 minutes

-inactivates complement but preserves antibodies.

Question 19

Describe the process occuring here.

Answer 19

Two IgG molecules are bound to a membrane. C1 has cross-linked the two IgGs, causing a conformational change in C1 to expose its active site.

Question 20

C5 convertase cleaves C5 into C5a and C5b. What are the major functions of C5a?

Answer 20

Phagocyte chemotaxis

Mast cell degranulation

Neutrophil activation

Question 21

What is the function of mannose-binding lectin (MBL)?

Answer 21

Binds to mannose molecules present on pathogen surfaces.

Functionally similary to C1. Initiates the lectin pathway of complement activation.

Question 22

What is meant by the term “terminal pathway” in terms of the complement cascade?

Answer 22

The end pathway common to all 3 complement activation pathways that results in formation of the MAC.

Once C5 is cleaved, the terminal pathway is initiated.

Question 23

What molecule is pictured here?

Answer 23

Membrane attack complex (MAC).

Question 24

How is the alternative pathway activated?

Answer 24

C3 in the plasma slowly degrades into C3a and C3b on a regular basis. If C3b binds to a microbial surface, Factor B will bind, creating a C3 convertase (different molecule, but same action as in the other 2 pathways).

This results in more C3 cleavage and activation of the complement system.

Question 25

How is the alternative pathway regulated?

Answer 25

C3 in the plasma slowly degrades into C3a and C3b on a regular basis.

Mammalian cells contain sialic acid, which binds factor H. If C3b binds to a mammalian cell, it is quickly destroyed by factors H and I.

Bacterial cells lack sialic acid. If C3b binds, the complement system is quickly activated.

Question 26

In general, what are the four biological consequences of complement activation?

Answer 26

Cell lysis

Vasodilation / Increased vascular permeability

Chemotaxis

Opsonization

Question 27

What process is pictured here?

Answer 27

C1 binding to IgM.

Note that only 1 IgM molecule is needed for C1 to bind.

Question 28

Where are complement molecules produced?

Answer 28

Liver