Basic Complement

Question 1

What are the complement pathways?

Answer 1

Classical (adaptive)
Alternative (innate)
Lectin (innate)

Question 2

C3 convertase cleaves C3 into what?

Answer 2

C3a – stimulates inflammation; chemoattractant for neutrophils

C3b – Attaches to microbial surface as opsonin; Attracts phagocytosis

Question 3

C3 convertase binds with C3b to form what?

Answer 3

C5 convertase

Question 4

C5 convertase cleaves C5 into what?

Answer 4

C5a – Soluble; Very potent chemoattractant that induces changes in permeability of blood vessels

C5b – Initiates formation of MAC

Question 5

What does the complement system work in cooperation with?

Answer 5

• • Blood coagulation pathway

- - Kinin-Kallikrein pathway (regulates vascular permeability)

Question 6

How is the alternative pathway activated?

Answer 6

Via autoactivation because of a process called “tickover” of C3

***Tickover occurs spontaneously to C3, generating C3a and C3b

Question 7

(AP) C3b is capable of binding ________ that can be cleaved into _____ and ______ by the constitutively active serum protease ________.

Answer 7

Factor B
Ba
Bb
Factor D

Question 8

(AP) The Bb associates with C3b, which forms _________. This can then cleave additional C3 molecules, generating more C3b.

Answer 8

C3 convertase (C3bBb)

Question 9

(AP) The successive proteolytic steps is enhanced by a serum protein _________, which stabilizes C3bBb interactions during the process.

Answer 9

Properdin

Question 10

Explain the formation of the MAC complex.

Answer 10

• • C5b binds C6 and C7
• • C5b67 complexes bind to membrane via C7
• • C8 binds to complex, inserts into membrane
• • C9 binds to complex, polymerizes
• • 1-16 molecules of C9 bind to form pore in membrane

Question 11

This pathway is Ab-mediated.

Answer 11

Classical pathway (CP)

Question 12

(CP) A plasma protein called _____ recognizes and binds to Ag-Ab complexes (hence why it’s ADAPTIVE immunity).

Answer 12

C1q

Question 13

(CP) Once C1q binds to the ______ portion of Abs, two associated serine proteases, called ______ and ______, become active.

Answer 13

Fc
C1r
C1s

Question 14

(CP) C1r activates C1s so that it can, in turn, activate _____ and ______.

Answer 14

C2

C4

Question 15

What is the C3 convertase complex for the CP and LP? The C5 convertase complex?

Answer 15

C4bC2a

C4bC2aC3b

Question 16

How is the Lectin pathway activated?

Answer 16

Binding of Mannose-binding Lectin (MBL) to bacterial surface and activation of MBL-associated serine proteases MASP1 and MASP2

Question 17

(LP) MBL recognizes terminal mannose residues on microbial glycoproteins and glycolipids (similar to the mannose receptor on _______).

Answer 17

Phagocytes

Question 18

(LP) After MBL binds to microbes, two zymogens called ______ and ______ are activated. These have similar functions to C1r and C1s, and initiate downstream cascade IDENTICAL to the CP.

Answer 18

MASP1

MASP2

Question 19

The CP requires what Abs to activate it?

Answer 19

IgM
2x IgG
C1

Question 20

What are the complexes for C3 convertase and C5 convertase for the alternative pathway?

Answer 20

C3bBb

C3bBbC3b

Question 21

The cleavage of C3b and C4b by ________ prevents them from forming active convertases and requires cofactor activity.

Answer 21

Factor I

Question 22

For C3b, the cofactors needed with Factor I are…

Answer 22

MCP
CR1
Factor H

Question 23

For C4b, the cofactors needed with Factor I are…

Answer 23

MCP
CR1
C4BP

Question 24

These cofactors inhibit assembly of new C3 convertases and shorten the half-life of the preformed convertases. For the classical pathway they are…

Answer 24

DAF
CR1
C4BP

Question 25

These cofactors inhibit assembly of new C3 convertases and shorten the half-life of the preformed convertases. For the alternative pathway they are...

Answer 25

DAF CR1 Factor H

Question 26

The MAC is the lytic complex of complement and its assembly can be inhibited by...

Answer 26

CD59 Vitronectin S protein

Question 27

Complement is not activated on the surface of (BACTERIAL/MAMMALIAN) cells because they express regulatory proteins that inhibit, disassemble, or cleave the convertases.

Answer 27

Mammalian

Question 28

These inflammatory mediators are often released from phagocytes after adhesion of soluble complement fragments.

Answer 28

PG (prostaglandins) ROS (reactive oxygen species) RNS (reactive nitrogen species)

Question 29

Most _______ diseases are immunology in origin. They are the result of either the deposition of immune complexes or the result of Abs directly binding to Ags in the kidney.

Answer 29

Glomerular

Question 30

T/F. CP attracts neutrophils via C5a and C5b-9 form the MAC. The production of ROS and inflammatory cytokines by the attracted inflammatory cells and production of proteases are both though to play a pathogenic role in glomerulonephritis.

Answer 30

True

Question 31

This is the inflammation of the vessels, which most commonly has an infectious or immune-mediated cause.

Answer 31

Vasculitis

Question 32

Immune-Mediated vasculitis occurs due to one of two mechanisms, which are...

Answer 32

- - Immune-complex deposition | - - Direct antibody interaction

Question 33

Abs induced by the disease process bind Ags. This interaction forms an immune complex (IC) that deposits within the vessel wall. Deposition of the ICs causes vasculitis through the ________ pathway of complement activation.

Answer 33

Classical

Question 34

This is a very rare and potentially life-threatening genetic condition. Symptoms include edema in various parts of the body, excruciating abdominal pain, nausea, and vomiting due to swelling in intestinal wall. Swelling of the airway or throat can cause death by asphyxiation.

Answer 34

Hereditary angioedema (HAE)

Question 35

HAE patients have a defect in the gene that controls a blood protein called _______. This defect causes a biochemical imbalance that produces swelling.

Answer 35

C1 inhibitor (C1-INH) ***HAE is also known as C1 Inhibitor Deficiency

Question 36

T/F. C1-INH can inactivate enzymes that are not part of the complement cascade, so without it there is continuous activation of the plasma complement.

Answer 36

True

Question 37

C1-INH also inactivates plasma kallikrein, an enzyme that cleaves a plasma kininogen to produce _________. This is the cause of the swelling seen in HAE (because C1-INH is deficient and can't inactivate the kallikrein).

Answer 37

Bradykinin

Question 38

This disease is a striking example of the consequences of the failure to regulate the formation of MAC. It is a somatic mutation that causes a deficiency of ______.

Answer 38

Paroxysmal Nocturnal Hemoglobinuria (PNH) | GPI

Question 39

PNH cells lack all the proteins linked through the GPI anchor to their cellular membranes. Two of the most important GPI anchor proteins are ______ and ______. These are complementary regulatory proteins involved in protecting the RBCs from the action of complement. Without these, RBCs are more susceptible and intravascular hemolysis can occur.

Answer 39

DAF (CD55) | CD59

Question 40

This is on the surface of all cells and inhibits C3 convertases and C5 convertases by inducing rapid dissociation of C2a or Bb.

Answer 40

DAF

Question 41

This inhibits the formation of the MAC by binding to sites on C8 and C9, thus blocking the uptake and incorporation of multiple C9 molecules into the complex.

Answer 41

CD59