Complement

Question 1

Which system is an immune surveillance system of plasma proteins that act in cascades to selectively kill extracellular pathogens and diseased tissue, promote inflammation, clear tissue damage and relate tissue homeostasis?

Answer 1

Complement system

*Most components made in Liver, make up 15% of plasma globulin protein, pattern recognition system

Question 2

What are the 3 pathways of the complement system?

Answer 2

1-Classical pathway
2-Lectin pathway
3-Alternate pathway

Question 3

What are the 7 categories of complement components?

Answer 3

1-Initiators
2-Convertase activators
3-Opsonins
4-Anaphylatoxins
5-Membrane attack complex (MAC)
6-Complement receptors
7-Regulators

Question 4

When a complement protein is cleaved, what are the two parts it breaks into?

Answer 4

• A portion (small fragment w/no enzymatic activity, signals activity
• B portion (Large fragment w/ enzyme activity, opsonic, signals activity)

Question 5

What is the exception to the A and B nomenclature of complement proteins?

Answer 5

C2 (a is the large, b is the small)

Question 6

Third to act, which complement pathway involves c-reactive protein or antibodies binding to specific antigens on pathogen surface to activate?

Answer 6

Classical pathway

Question 7

C1q binds ________ bound Pentameric IgM molecules while it needs at least ______ bound IgG molecules

Answer 7

1, 2

*binding of C1q activates C1r which cleaves and activates serine protease C1s

Question 8

In the classical pathway, C1qr2s2 binds antibodies and cleaves C4 protein which leads to what?

Answer 8

C4b binding to the cell surface

Question 9

In the classical pathway, C4b does what once bound to the cell surface?

Answer 9

Cleaves C2, forming C4b2a, a C3 convertase

Question 10

In the classical pathway, C4b2a cleaves C3 to form C4b2a3b, a C5 convertase, leading to what?

Answer 10

Cleaving of C5 into C5b (opsonizes) and C5a (signals)

Question 11

Second to act, which complement pathway is mannose-binding to pathogen surface?

Answer 11

Lectin pathway

*Yeast especially contain many terminal mannose residues. Vertebrates have terminal sialic acid residues

Question 12

The lectin pathway is initiated by mannose binding lectins (MBL) and ficolins and then recruits what two?

Answer 12

MBL associated serine proteases (MASP)

• MASP-1
• MASP-2

Question 13

MBL have trimeric clusters of carbohydrate-recognition domains and bind what?

Answer 13

Mannose and fucose residues with high avidity

Question 14

Ficolins have trimeric clusters of carbohydrate-recognition domains and bind what?

Answer 14

Oligosaccharides containing acetylated sugars

Question 15

What does MASP-1 and 2 cleave when activated by associating with MBL of ficolin?

Answer 15

C4

*C4b then binds the surface

Question 16

What is also cleaved by MASP-1 and 2 and then binds with C4b?

Answer 16

C2

*C2a binds with C4b to form C3 convertase C4b2a

Question 17

In the lectin pathway, C4b2a does what?

Answer 17

Cleaves C3 to C3a and b. C3b bines to the surface or convertase itself

*can cleave up to 1000 molecules of C3

Question 18

First to act, which complement pathway is activated by pathogen surface creating a local environment conducive to complement?

Answer 18

Alternative pathway

Question 19

What are the 3 routes of activation of the alternative pathway?

Answer 19

1-Spontaneous C3 hydrolysis
2-Properdin-pathogen binding and C3 recruitment
3-Proteolytic C3 cleavage (thrombin, clotting cascade proteases)

Question 20

Exposure of the thioester bond by cleaving C3 is typically of which route of activation for the alternative pathway?

Answer 20

Spontaneous C3 Hydrolysis

*either attacked by H20 to be soluble or C3b binds pathogen surface

Question 21

What are the two C3 convertases that are responsible for the spontaneous C3 hydrolysis activation of the alternative pathway?

Answer 21

1-iC3Bb (initiates alternative pathway, soluble)

2-C3bBb (drives pathogen C3b opsonization, attached to membrane)

Question 22

Once bound to C3, B complement is cleaved by what to form iC3Bb?

Answer 22

Complement D

*Same thing cleaves B to form C3bBb when C3bB is bound to membrane

Question 23

What protein can bite to C3bBb on pathogen surfaces to stabilize it and drive the reaction forward in the Spontaneous C3 hydrolysis pathway?

Answer 23

Properdin

Question 24

Properdin can also bind cell surface, subsequently forming C3bPB by binding C3b and factor B to cleave Factor D, forming C3bPBb as part of of what pathway?

Answer 24

Properdin-Pathogen binding activation of alternative pathway

*C3bPBb is the same as C3bBb from spontaneous C3 hydrolysis once Properdin is bound

Question 25

What other Complement protein is also activated by the alternative pathway and is cleaved by C3b2Bb?

Answer 25

C5

*C5b opsonizes

Question 26

What 3 things to bound C3b proteins facilitate?

Answer 26

1-Recruitment of inflammatory cells
2-Opsonization of pathogens, facilitating uptake and killing by phagocytes
3-Perforation of cell membrane

Question 27

Known as anaphylatoxins, the small complement cleavage products do what?

Answer 27

Act on blood vessels to increase vascular permeability and cell-adhesion molecules

*More macrophages, PMNs, and antibodies can then flood the site

Question 28

When C3b is bound to the bacteria and then binds to Cr1 on a macrophage, what else also must bind to induce phagocytosis?

Answer 28

C5a

*act as a checkpoint

Question 29

Factors H and I both serve what purpose?

Answer 29

Inactivate C3b by cleaving into iC3b

Question 30

DAF(Decay accelerating factor) and MCP (membrane co-factor protein) serve what purpose?

Answer 30

Disrupt C3 convertase C3bBb on human cell surface

*healthy cells express these, unhealthy cells dont

Question 31

C5b recruites C6,7,8,and 9 which recruits more C9 to make what?

Answer 31

Membrane Attach Complex (MAC) which forms pores in cell membrane

Question 32

In humans, what binds to C5b678 to prevent the formation of a pore in the Membrane Attack Complex?

Answer 32

CD 59

*prevents recruitment of C9 to form the pore