L16: Complement

Question 1

Classical pathway activation is initiated after

Answer 1

immune complex formation.

Question 2

Complement component C1 recognizes the

Answer 2

antigen-antibody complex.

Question 3

The binding of antibody to antigen induces a conformational change in the

Answer 3

antibody constant region.

Question 4

Binding of antibody to antigen exposes a site on the Fc portion (of the antibody molecule) that can be bound by

Answer 4

C1, the first complement component of the classical pathway

Question 5

C1 is a macromolecule that consists of….

Answer 5

C1q (comprised of 6 globular heads and extended tails) in complex with C1r and C1s (the C1qrs complex).

Question 6

Activation of the C1qrs complex occurs when

Answer 6

at least two of the C1q globular heads are simultaneously bound to antibody………for this to occur, two Fc portions need to be in within close molecular proximity of each other on the antigenic surface.

Question 7

In contrast to IgG, the pentameric nature of IgM allows

Answer 7

a single molecule of antigen bound IgM to activate C1.

Question 8

Once C1q is bound to antibody, C1r undergoes a

Answer 8

conformational change and becomes enzymatically active.

Question 9

…C1r then cleaves ___

Answer 9

C1s, which after cleavage is enzymatically active as well.

Question 10

Unlike the classical activation pathway, the Lectin pathway is initiated by a protein called

Answer 10

Mannose Binding Lectin (MBL) or ficolins, which are homologous to C1q.

Question 11

MBL binds to mannose and certain other complex carbohydrates that are found on the surface of many microbial pathogens like…

Answer 11

Candida albicans, a fungus with surface mannose residues

Question 12

MBL/ficolins are physically associated with two serine proteases, called

Answer 12

MASP-1 and MASP-2 (mannan binding lectin-associated serine protease-1) that are similar to C1r and C1s.

Question 13

MASP-1 and MASP-2 are similar to

Answer 13

C1r and C1s.

Question 14

When MBL/ficolins bind to surfaces

Answer 14

MASP-1 and MASP-2 become activated.

Question 15

_______ are similar in structure to MBL, but have different carbohydrate binding proteins

Answer 15

Ficolins

Question 16

In the classical pathway, which of the following bind to Fc of the antibody?
A. C1q
B. C1s
C. C1r

Answer 16

A. C1q

Question 17

Which Ig subtypes can activate complement?

Answer 17

IgG and IgM

Question 18

Why don’t circulating unbound IgG and IgM activate the complement system?

Answer 18

A conformational change is required in the Fc region that will activate complement. This conformational change only occurs when IgM or IgD is bound to antigen.

Question 19

What complement proteins recruit phagocytic cells to the site of infection and promote inflammation?

Answer 19

C3a, C5a

Question 20

Phagocytes with receptors for which complement protein, engulf and destroy the pathogen?

Answer 20

C3b

Question 21

MAC is composed of

Answer 21

C5b, C6, C7, C8, C9

Question 22

To what residues does MBL bind

Answer 22

mannose and fucose residues

Question 23

To what residues does Ficolin bind?

Answer 23

acetylated sugars

Question 24

Which pathway depends on spontaneous hydrolysis of C3?

Answer 24

Alternative pathway

Question 25

The removal of antigen-antibody complexes from the circulation depends upon

Answer 25

C3b.

Question 26

Via C3b, antigen-antibody complexes bind to complement receptors on

Answer 26

circulating red blood cells.

Question 27

C1 inhibitor?

Answer 27

C1 INH. inhibits C1 by dissociating C1r and C1s from the C1 complex.

Question 28

Name 5 inhibitors of C3 convertase

Answer 28

Decay-accelerating factor (DAF) C4-binding protein (C4BP) Complement receptor 1 (CR1) Membrane cofactor protein (MCP) Factor I (I)

Question 29

Name 3 inhibitors of C5 convertase

Answer 29

``` Factor I (I) Factor H (H) Complement receptor 1 (CR1) ``` note: CR1 inhibits both C3 and C5 convertases!

Question 30

What inhibits MAC formation

Answer 30

CD59

Question 31

MAC deficiency can lead to

Answer 31

infection with Neisseria spp only

Question 32

C3b deposition deficiency

Answer 32

Infection with pyogenic bacteria and Neisseria spp. is associated with defects in

Question 33

Hereditary Angioneurotic Edema is associated with deficiency in

Answer 33

C1 INH. Failure to regulate C1 resulting in fluid accumulation, epiglottal swelling.

Question 34

Paroxysmal Nocturnal Hemoglobinurea is associated with deficiency in

Answer 34

CD59. Leads to RBC lysis because now RBC's have nothing to defend against MAC attack.

Question 35

A deficiency of the early components of complement results in poor clearance of...

Answer 35

immune complexes, resulting in increased immune complex disease.

Question 36

A deficiency of complement component C9 results in susceptibility to: ``` A. Pyogenic bacteria. B. Neisseria spp. only. C. Immune complex disease. D. Reduced immune complex clearance. E. No phenotype. ```

Answer 36

B. Since C9 is part of the MAC, and MAC deficiency results in Neisseria infection