Lecture 6 - Complement System

Question 1

What is complement

Answer 1

A group of serum and cell surface proteins activated by
factors such as the combination of antigen and antibody

Question 2

What does complement result in

Answer 2

generation of enzyme cascades that have a variety of biological consequences including cell lysis and
opsonization

Question 3

What are the 3 pathways to activate complement

Answer 3

1. classical
2. alternative
3. MB-lectin

Question 4

When is the classical pathway initiated

Answer 4

when a complement fixing antibody (IgM, IgG) binds
antigen

Question 5

What immunities are involved in the classical pathway

Answer 5

innate AND adaptive

Question 6

Does the classical pathway occur in a primary response

Answer 6

YES

Question 7

What happens in the classical pathway after the antibody is bound to antigen?

Answer 7

binding site for complement on Fc portion of the antibody opens up

Question 8

What is the alternative pathway initiated by

Answer 8

C3b binding on the cell wall of pathogens

Question 9

What is the most abundant complement protein in the blood

Answer 9

C3

Question 10

What does C3 spontaneoulsy break down to in the alternative pathway

Answer 10

C3a and C3b

Question 11

What happens when C3 b binds to mammalian cells

Answer 11

it is quickly innactivated

Question 12

What immunity is the alternative pathway part of

Answer 12

INNATE

Question 13

What immunity is not required for the alternative pathway to be innitiated

Answer 13

ADAPTIVE

Question 14

What is the MB-lectin pathway initiated by

Answer 14

soluble pattern recognition molecules (PRR) that bind to carbohydrates on the microbe surfaces

Question 15

What does MB-lectin pathway activate

Answer 15

enzymes that activate complement

Question 16

What immunity is MB-lectin pathway part of

Answer 16

INNATE

Question 17

What immunity is not required to activate the MB-lectin pathway

Answer 17

ADAPTIVE

Question 18

Why is MBL pathway initiated on bacteria cells but not self-cells

Answer 18

mammalian cells do not have mannose on their surface

Question 19

Where do the three complement pathways differ

Answer 19

initiation of the cascade

Question 20

Where are the three complement pathways the same from

Answer 20

C3 through the terminal pathway and formation of the membrane attack complex (MAC)

Question 21

What complement pathways are part of the innate defense

Answer 21

Alternative and MBL pathways

Question 22

What pathways require adapte immune response to initiate

Answer 22

classical pathway

Question 23

What does classical pathway require

Answer 23

IgM and IgG

Question 24

What BINDING initiaites the classical pathway

Answer 24

Ag-Ab binding

Question 25

What happens after the Ab binds the Ag in the classical pathway

Answer 25

conformational change in the Fc portion of Ab that allows C1, the first protein of the complement cascade to bind to the Ag-Ab complex

Question 26

Why is one IgM or two IgG required for initiation

Answer 26

there must be 2 Fc binding sites for C1 to bind

Question 27

What is more efficient at activating the classical pathway of complement

Answer 27

IgM

Question 28

How many IgM bound to Ag can initiate the classical complement cascade

Answer 28

ONE pentameric IgM

Question 29

How many IgG can activate C1 in the classical pathway

Answer 29

TWO IgG molecules in CLOSE PROXIMITY

Question 30

What does activated C1 cleave in the classical pathway

Answer 30

C4 into C4a and C4b

Question 31

What binding event occurs in the classical pathway after C1 cleaves C4?

Answer 31

C4b binds to a membrane and C2 binds to membrane bound C4b

Question 32

What does C1 do in the classical pathway after C4b binds to the membrane

Answer 32

cleaves C2 when it is bound to C4b, leading to formation of C4bC2b

Question 33

What is the C4b2b in the classical pathway

Answer 33

C3 convertase

Question 34

What is the classical pathway C3 convertase

Answer 34

C4b2b

Question 35

What does C3 convertase cleave in the classical pathway

Answer 35

3 into C3a and C3b

Question 36

What molecule in the classical pathway is an opsonin

Answer 36

C3b

Question 37

What are pathogens opsonized with in the classical pathway

Answer 37

C3b

Question 38

What leads to initiation of the terminal pathway

Answer 38

C3b binds C5 and C4bC2b cleaves C5

Question 39

ACTIVATION of the ALTERNATIVE pathway 1. C3 sponatneously breaks down into ___ and ____ 2. C3b's reactive carbonyl group will ______ 3. ____ can bind to C3b 4. _____ can cleave Factor B bound to C3b 5. _____ is the alternative pathway C3 convertase

Answer 39

1. C3a and C3b 2. covalently bind to cell surfaces 3. Factor B 4. Factor D 5. C3bBb

Question 40

What is the alternative pathway C3 convertase

Answer 40

C3bBb

Question 41

ACTIVATION of the MBL pathway 1. MBL is a _______ 2. MBL binds to ______ on microbes 3. Bound MBL activates _______, which has similar activity to ____ 4. MASP-2 cleaves ___ and the cascade is initiated

Answer 41

1. soluble PRR 2. mannose (a PAMP) 3. MASP-2, C1 4. C4

Question 42

What part of the complement cascade is the same for all 3 pathways

Answer 42

terminal complement pathway

Question 43

What initiates the terminal pathway

Answer 43

cleavage of C5

Question 44

What are not involved after initiation of the terminal pathway

Answer 44

enzymes

Question 45

What does initiation of the terminal pathway lead to formation of

Answer 45

membrane attack complex

Question 46

What occurs with the MAC when C5 binds to C3b

Answer 46

it exposes a site on C5b that can bind C6 and C7

Question 47

What occurs after the site on C5b that can bind C6 and C7 is exposed

Answer 47

C5b67 binds C8 and inserts into the membrane

Question 48

What occurs after C5b67 binds C8 and inserts into the membrane

Answer 48

C5b678 damages the membrane and induces polymerization of C9

Question 49

What is involved in polymerization of C9

Answer 49

12-18 molecules of C9 polymerize and form a transmembrane pore

Question 50

What is the result of polymerization of C9

Answer 50

lysis and cell death

Question 51

What is a regulator of classical activation

Answer 51

C1-INH

Question 52

What is a regulator of C3

Answer 52

CD59

Question 53

What is a regulator of the alternative pathway

Answer 53

Factor H

Question 54

What effect does C1 have onC2

Answer 54

NONE

Question 55

What effect does C1 have on C4b2

Answer 55

Cleaves into C4b2b and C2a

Question 56

What effect does D have on B

Answer 56

none

Question 57

What effect does D have on C3bB

Answer 57

cleaves into C3bBb and Ba

Question 58

What effect does C4b2b have on C5

Answer 58

none

Question 59

What effect does C4b2b have on C3b5

Answer 59

cleaves into C3b5b and C5a

Question 60

What biological consquence of complement activation does C2a have

Answer 60

increased vascular permeability

Question 61

What biological consquence of complement activation does C3a have

Answer 61

anaphylatoxin and microbial killing

Question 62

What biological consquence of complement activation does C3b have

Answer 62

immune regulation and opsonization

Question 63

What biological consquence of complement activation does C5a have

Answer 63

-neutrophil chemotaxis -anaphylatoxin -lysosomal enzyme secretion -neutrophil activation -increased vascular permeability -smooth muscle contraction

Question 64

Overall result of opsonization and phagocytosis

Answer 64

phagocytosis and killing of microbe

Question 65

Overall result of complement-mediated cytolysis

Answer 65

osmotic lysis of microbe

Question 66

Overall result of stimulation of inflammatory reactions

Answer 66

destruction of microbes by leukocytes

Question 67

Complement proteins are found in _____

Answer 67

normal serum

Question 68

Complement components may form a terminal complement complex and _______

Answer 68

punch holes in microbes