BIOL 435 Ch. 5 Part One (The Complement System)

Question 1

complement (C’) system

Answer 1

• group of serum proteins circulating in inactive form

- once activated, multiple possible outcomes

Question 2

multiple possilbe outcomes (C’ system activated)

Answer 2

• target cell membrance lysis (MAC)
• chemotaxis
• opsonization to enhance phagocytosis
• inflammation

Question 3

functional categories of C’ proteins

Answer 3

• initiators
• convertase activators
• enzymatic mediators
• opsonins
• anaphylatoxins
• membrance attack complex
• complement receptors
• regulators

Question 4

3 pathways in C’ system

Answer 4

-classical
-lectin
-alternative
*all generate C3b
>an important, multifunctional C’ protein

Question 5

classical pathway

Answer 5

-IgM or IgG binds to a multivalent Ag
>allows binding of C1q
-C1 finds Fc on adjacent IgG molecules or IgM bound to Ag
*need at least 2 Ab

Question 6

binding of C1q

Answer 6

-begins the process of C’ deposition

Question 7

C1qr2s2

Answer 7

-inititates a cascade of reactions enabling the next reaction in the sequence

Question 8

C1 binding followed by

Answer 8

• cleavage of C4: C4b bound to pathogen membrane
• then cleaveage of C2
• C4b2a

Question 9

C4b2a

Answer 9

-bound to cell surface
=C3 convertase
-cleaves many C3 proteins

Question 10

C5 convertase

Answer 10

=C4b2a3b

• C3 converts and C3 proteins
• cleaves C5 protein
• embedded in membrane

Question 11

C3a and C5a

Answer 11

-anaphylotoxin: promotes inflammation

Question 12

when C4 is cleaved

Answer 12

-a thioester bond is exposed on C4b (or C3b)
>reactive
>binds amino groups on target surface
>bonding must happen quickly
-if no target is present, bond is hydrolyzed and rendered inert
*90% don’t get bound

Question 13

C3b (+C4b)

Answer 13

• bind microbial surfaces: opsonization
• attach to Fc of Ab
• bind Fc receptors on macrophages and RBC and are cleared

Question 14

Ag

Answer 14

-large
-substance that generates an immune response
-a single Ag, may have many BCR specific for it
>only a small part binds to BCR/Ab

Question 15

epitopes

Answer 15

-antegenic determinant
-1 to 6 monosaccharides
-5 to 8 AAs
-small pieces of Ag
-any Ag can have multiple of them
-based on shape or linear sequence
>may ‘change’ when Ag changes shape

Question 16

C1r

Answer 16

-cleaves the other C1r, then cleaves C1s2

>C4 clevage

Question 17

C5b

Answer 17

• embedded in membrane

- begins membrance attack complex (MAC)

Question 18

common components in all 3 pathways

Answer 18

1. *C3b: opsonin
2. MAC
3. C3a and C5a: anaphylotoxin

Question 19

Ag/Ab complexes/clusters

Answer 19

-bring together all Ag and make them more visible

>more likely to be cleared

Question 20

lectin pathway initated

Answer 20

-when soluble proteins recognize microbial CHO antigens

Question 21

lectins

Answer 21

• bind to microbial surfaces
• serve as docking sites for MBL-associated serine proteases (MASPs)
  ex. MBL

Question 22

MASPs

Answer 22

-MBL-associated serine proteases
-cleave C4 and C2 to form the C3 convertase
>subsequent steps are same as the classical pathway (forms C5 convertase)

Question 23

3 ways alternative C’ pathway is initiated

Answer 23

1. Tickover pathway
2. Properdin-activated pathway
3. Protease-activated pathway

Question 24

alternative C’ pathway no matter how it starts

Answer 24

• actived C3b binds to membrane of target cell
• factor B (fB) binds and is cleaved by factor D (fD) =Bb
• C3bBb=C3 convertase
• Properdin (fP) stabilizes the C3 convetase

Question 25

tickover pathway-always on

Answer 25

-C3 is constantly made and inactivated 1. Spontaneous hydrolysis of C3=C3(H2O) 2. C3(H2O) bind fB 3. fB is cleaved by fD 4. C3(H2O)Bb is a 'fluid-phase convertase' >cleaves C3

Question 26

tickover pathway if membrane around

Answer 26

1. Some C3b bind to microbial surface 2. C3b binds fB >cleaved by fD=C3bBb 3. C3bBb=membrane bound C3 convertase >stabilized by Properdin 4. Another C3b binds >C3bBbC3b formed=C5 convertase

Question 27

Properdin pathway

Answer 27

1. Properdin can directly bind to a surface 2. Can recruit C3b and fB >fD recruited, cleaving fB into Bb 3. C3bPBb=active C3 convertase 4. Identical to tickover pathway

Question 28

protease-activated pathway

Answer 28

-initiation of clotting cascades can stimulate cleave of C' proteins >thrombin cleaves C3 and C5 >platelet activation *strong inflammatory reactions could activate C' systems

Question 29

platelet activation

Answer 29

-releases ATP, calcium ions and serine/theronine kinases | >can stabilize C3b in fluid phase

Question 30

C5 initiates

Answer 30

-generation of MAC

Question 31

MAC

Answer 31

- membrane attack complex - result of deposition of C5b, C6, C7, C8 and C9 in target cell membrane =pore structure * disrupts osmotic integrity, resulting in cell death

Question 32

MAC formation

Answer 32

- C6 embeds - C7 embeds - C8 all the way through - C9 produce massive hole: many of them come together

Question 33

cell 'fights' MAC

Answer 33

- endocytosis if only a few | - exocytosis and release them