Complement Class 1

Question 1

What is complement?

Answer 1

a complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to enhance host defense mechanisms against foreign cells

Question 2

The Discovery of Complement

Answer 2

• by Jules Bordet, early 1890s
• Sheep antiserum against Vibrio cholerae was no effective if heated above 56 degrees
• ABs not denatured at 56 degrees
• Must be second component
• Added AB depleted serum to heated sera-restored lytic activity
• “complements” activity of AB

Question 3

Where are more plasma complement proteins synthesized?

Answer 3

in the liver, with the exception of C1 components, which are mainly produced by intestinal epithelial cells, and factor D, which is made in adipose tissue

Question 4

What are zymogens?

Answer 4

Inactive precursor proteins that are converted to active enzymes in the complement system
ex -

Question 5

What are the three different ways complement can be activated?

Answer 5

Classical pathway, Alternative pathway, Lectin pathway

Question 6

Classical pathway (Complement activation)

Answer 6

which involves nine proteins that are triggered by antigen–antibody combination

• originally called properdin system
• activated by IgM,IgG1-4, IgA, IgE - few substances can bind complement directly to initiate the classical cascade

Question 7

Alternative pathway (Complement activation)

Answer 7

antibody-independent means of activation of complement

Question 8

Lectin pathway (complement activation)

Answer 8

another antibody-independent means of activating complement proteins Its major constituent, mannose- (or mannan-) binding lectin (MBL), adheres to mannose found mainly in the cell walls or outer coating of bacteria, viruses, yeast, and protozoa.​ ​

Question 9

What are the functions of complement?

Answer 9

• major role in inflammatory reponse against foreign antigens
• end product is lysis of invading cell
• complements the functions of the innate and adaptive immune systems
• Lysis, opsonization, activation of the inflammatory response, clearance of immune complexes

Question 10

How are complement components named?

Answer 10

Primary Proteins - named on a numeric system Additional components - given a factor name Activated proenzymes - once cleaved, the smaller components have “a or b” added

Question 11

Anaphylatoxin

Answer 11

a small peptide that causes increased vascular permeability, contraction of smooth muscle, and release of histamine from basophils and mast cells
Ex - C3a, C4a, C5a

Question 12

chemotaxin

Answer 12

A protein or other substance that acts as a chemical messenger to produce chemotaxis.

Question 13

Opsonin

Answer 13

Serum proteins that attach to a foreign substance and
enhance phagocytosis (from the Greek word meaning “to prepare
for eating”).

Question 14

What are the three main stages of complement activation?

Answer 14

Recognition unit (C1), activation unit (C4,2,3), membrane attack complex/terminal sequence (C5-9)

Question 15

What are the components of the Recognition unit of the complement cascade?

Answer 15

C1qrs is the recognition unit that binds to the FC portion of two antibody molecules. C1s is activated and cleaves C4 and C2 to form C4b2a
(C1qrs + ABs FC –> C1s activation –> C4 and C2 cleavage –> C4b2a)

Question 16

What changes happen to the structure of the C1rqs during the change from inactive to active?

Answer 16

Structure of C1qrs. When two or more globular heads of C1q attach to bound immunoglobulin molecules, the collagen like stalks change their configuration.
The resulting shape change causes C1r to become a serine protease, which cleaves a small fragment of C1s, uncovering the C1s protease, whose only targets are C4 and C2.

Question 17

What are the components of the Activation unit of the complement cascade?

Answer 17

C4b2a, also known as C3 convertase –> cleaves C3 to form C4b2a3b (aka C5 convertase) the combination of C4b2a3b is the activation unit

Question 18

Terminal sequence of Complement components

Answer 18

• common to all activation pathways

- C5 convertases cleave C5 into C5a and C5b

Question 19

compare C5a to C3a. Why is one more potent than the other?

Question 20

Membrane Attack complex

Answer 20

Circular polymer of C9 molecules that for a pore in cell surface​
​
Pores allow free ion and water exchange leading to osmotic swelling and cell rupture​

Question 21

What are the characteristics / determining factors of the classical pathway?

Answer 21

1 - Initiated by binding of antibody ​
2 - C1q proteins link bound antibody molecules by binding sugar residues on Fc region of IgG and IgM molecules​

(Cannot bind to just one antibody molecule-needs to bridge molecules​ - 2 or more IgG monomers​/ 1 pentameric IgM complex​)
(C1q is not enzymatic​)

3 - Requires association of other serine proteases C1r and C1s​”

Question 22

How does IgM binding influence the Classical pathway?

Answer 22

Cannot bind in “planar” conformation is serum​

Only binds to “staple” conformation bound to cells​

Question 23

Anaphylatoxin

Answer 23

“a small peptide that causes increased vascular permeability, contraction of smooth muscle, and release of histamine from basophils and mast cells Ex - C3a, C4a, C5a”