Complement system

Question 1

What does the activation of the complement pathway involved?

Answer 1

Sequential proteolytic cleavage of substrates that results in a cascade reaction

Question 2

what are the 4 main functions of the complement system?

Answer 2

1. lyse target cells
2. promote phagocytosis 3. induce inflammatory response
3. clear immune complexes

Question 3

activation of the classical complement pathway requires one or more:

Answer 3

antibody-antigen complexes

Question 4

What is the alternative complement pathway involved in?

Answer 4

Innate immunity and can function in the absence of antibody

Question 5

What triggers the alternative pathway ?

Answer 5

A range of microbial molecules as well as nonpathogenic molecules

Question 6

What initiates the alternative pathway?

Answer 6

spontaneous hydrolysis of C3

-C3b then deposits on the microbial surface

Question 7

Which protein is key in maintaining the activation of the alternative pathway by stabilization?

Answer 7

Properdin

• stabilizes C3bBb
• also called factor P

Question 8

What is the lectin pathway involved in ?

Answer 8

Innate immunity

-does not depend on the presence of antibody

Question 9

What activates the lectin pathway?

Answer 9

Interaction of mannose binding lectin with mannose residues on glycoproteins/carbohydrates that are expressed by certain microorganisms

Question 10

what are the 2 MBL associated proteases generally found on the surface of microbes?

Answer 10

MASP-1 and MASP-2

Question 11

What is the role of MASP 1 and MASP 2

Answer 11

bind MBL on the microbe to form a complex that is able to cleave C4 and C2

Question 12

Where can the complement system be regulated?

Answer 12

Before AND after the assembly of C3 convertase

-very important to regulate it so that only the appropriate targets are being attacked

Question 13

What is C1 inhibitor and what does it do?

Answer 13

Induces dissociation and inhibition of C1r2s2 from C1q

is a serine protease inhibitor

affects the classical and lectin pathways

Question 14

What is Decay Accelerating Factor (DAF)

Answer 14

Accelerates the dissociation of C4b2a and C3bBb (both the C3 convertases)

Question 15

What is CR1 (CD55)

Answer 15

a membrane bound regulator of the complement pathway

Block formation of and accelerated dissociation of the C3 convertases by binding C4b and C3b

Question 16

What is the role of Protectin ?

Answer 16

Binds C5b678 on host cells to prevent the binding of C9 and the formation of the MAC

Question 17

What are 5 ways to turn off the complement pathway?

Answer 17

1. Dissociation of C1 components
2. Decay accelerating activity (DAF) for C3 convertases
3. Factor I cofactor activity (CR1)
   - degrades C3b and C4b`
4. Inhibition of lysis/MAC (protectin)
5. Cleavage of anaphylatoxins by carboxypeptidases

Question 18

What is the role of anaphylatoxins?

Answer 18

To attract leukocytes to the site of inflammation as well as to increase permeability in the vasculature

Question 19

What are the 3 anaphylatoxins?

Answer 19

C3a, C4a, C5a

Question 20

What are the special roles of C3a and C5a?

Answer 20

chemotactic for granulocytes and monocytes

Also cause platelet aggregation

Question 21

Opsonization of microbes is achieved by?

Answer 21

C3b, C3bi, C4b

Question 22

What is the role of RBC in the complement pathway?

Answer 22

CR1 on RBC interacts with C3b and carries small soluble complexes to the liver or spleen to be eliminated by phagocytes

Question 23

CR1, 2, 3, and 4 are?

Answer 23

Receptors that bind complement components and their breakdown parts

Question 24

What does CR1 bind and where is it expressed?

Answer 24

Binds: C3b, C4b, C1q, iC3b

Found on: RBC, neutrophils, monocytes, macrophages, eosinophils, FDCs, B cells, and some T cells

Question 25

What does CR2 bind and where is it expressed?

Answer 25

aka Epstein-Barr virus receptor

Binds: C3d, C3dg (products of factor I cofactor activity)

Found on: B cells and FDCs

Question 26

What does CR3 bind and where is it expressed?

Answer 26

Binds: iC3b and factor H

Found on: monocytes, macrophages, neutrophils, NK cells, eosinophils, FDCs, T cells

Question 27

What does CR4 bind and where is it expressed?

Answer 27

Binds: iC3b

Found on: monocytes, macrophages, neutrophils, NK cells, T cells

Question 28

What is the consequence of a breakdown int he clearance mechanism for complement?

Answer 28

some of the immune complexes deposit in the kidneys

-sometimes can occur post strep throat