Complement Systems

Question 1

What is the Complement Sysytem?

Answer 1

Group of about 30 serum proteins that interact in a cascade to kill bacteria.

Question 2

Are complement protein always present in the serum?

What activates them?

Answer 2

YES

Infection

Question 3

Where are complement proteins made?

What makes them?

Answer 3

In the liver under normal conditions

By Myeloid cells (during inflammation response)

Question 4

Three Pathways of Complement Activation….

Answer 4

1. Classical pathway
2. Alternative pathway
3. Lectin pathway

Question 5

Pathways of Complement activation that are part of the innate immune system….

Answer 5

1. Alternative pathway
   - Pathogen surface makes environment more likely to complement activation.
2. Lectin pathway
   - Mannose-biding protein binds pathogen surface

Question 6

Pathways of Complement activation that are part of the acquired immune system

Answer 6

1. Classical Pathway

- Antibody binds to SPECIFIC antigen on pathogen surface.

Question 7

When is each pathway of the complement system initiated? (Not just not just inflammatory response)

Answer 7

When a complement component in serum binds to the surface of a pathogen.

**Initial steps are diff. for each pathway

Question 8

Sequential activation….

Answer 8

A series of enzymes activate other complement proteins in SEQUENCE

Question 9

What happens during each step of sequential activation?

Answer 9

“Domino Effect”

An active complement enzyme cleaves (proteolyses) & activates the next enzyme in the pathway.

Question 10

Amplification…

Answer 10

Like At&t….We want more, we want more!!

Each complement enzyme activates MULTIPLE molecules of the next complement protein in the cascade.

Question 11

Regulation….

Answer 11

The Party Poopers….

Complement activity is tightly regulated to prevent uncontrolled or inappropriate activation.

Multiple regulatory proteins LIMIT DAMAGE to pathogens.

Question 12

What brings the 3 complement activation pathways 2gether?

Answer 12

Cleavage of C3 complement —-> C3B intermediate

Question 13

What is the abbreviation for complement proteins?

Answer 13

“CX”

X= 1-9

Question 14

What is used to designate complement fragments?

Answer 14

A lowercase letter usually a or b

Question 15

C3 9 = …….

Answer 15

C3a+ C3b

Question 16

“a” fragment…….

Answer 16

Soluble

Question 17

“b” fragment….

Answer 17

Remains cell-associated \

• Bigger than “a”

Question 18

Which complement protein has the fxn’s of “a” & “b” reversed?

Answer 18

C2

Question 19

“I”…..

Answer 19

Inactive

Fragments do NOTsupport complement activation.

**Have other biological functions. ( iC3b = C3bi)

Question 20

Subunits of C1….

Answer 20

C1q
C1r
C1s

Question 21

Convertase….

Answer 21

CONVERTS

Inactive complement protein—-> Active

• ** Cleaves it
• ***Composed of subunits.

Question 22

Proteins of Alternative Pathway….

Answer 22

Factor X

X= A capital letter.

Question 23

Complement receptors….

Answer 23

CR1, CR2, CR3 & CR4

Question 24

Activation of the classical cascade is initiated by….

Answer 24

The binding of C1 to an antigen-antibody complex.

** NEEDS antigen, antibody alone does NOT activate C1.

Question 25

What is needed to activate C1?

How many are needed?

Answer 25

1. One IgM

2. Two IgG molecules are recquired

Question 26

C1 Binding to the antibody results in…

Answer 26

Formation of the complex C4b2a (C4b + C2a).

***Series of enzymatic reactions.

Question 27

C4b2a complex….

Answer 27

C3 Convertase of Classical pathways

Question 28

C3 Convertase fxn?

Answer 28

Cleaves C3 to C3a and C3b

C3a: Biological activities

C3b: Forms a covalent bond w/ surface of the pathogen “b”= BOND