Test 1: lecture 5 complement

Question 1

___is an immune defense system that recognizes pathogens and altered cells and facilitates their elimination

Answer 1

Complement

Question 2

complement system is involved in ___ immunity

Answer 2

innate (first line of defense)

Question 3

complement system are a set of soluble proteins excreted by the ___ as ___

Answer 3

liver

zymogens (inactive/proenzymes)

Question 4

C3 is a central component of complement found in ___ and activated by ___

Answer 4

serum

protein cleavage

Question 5

C3 when cleaved turns into ___

Answer 5

C3a and C3b

Question 6

C3a acts as a ____

Answer 6

anaphylatoxin (recruits other immune cells)

Question 7

C3b will form a covalent bond to pathogen via ___

Answer 7

thioester

Question 8

how does C3b bind to surface

Answer 8

thioester reaction (S-C=O)

csy→gly→glu→Gln

cyst attached to a Gln and form a bond that is highly reactive to nucleophile (has electrons it wants to share)= amino group of a protein (NH2), hydroxyl group (OH), water

attacked by R-OH or R-NH2 will bind to surface of pathogen

if attacked by H20 will be inactivated/soluable

Question 9

what happens to C3b thioester bond when attacked by ROH or RNH2?

Answer 9

C3b will bind to pathogen surface

Question 10

what happens to thioester bond of C3b when it binds with H20

Answer 10

will be inactivated/soulable

Question 11

___ converts C3 → C3b

Answer 11

convertase

Question 12

MBL

Answer 12

mannose binding lectin

Question 13

what are the two zymogen proteases on the MBL?

Answer 13

mannose binding lectin

2 serine protease zymogens= MASP-1 and MASP-2

Question 14

lectin- a protein or domain binds to ___

Answer 14

carbohydrates (carbohydrate recognition domains CRD)

mannose binding lectin (MBL

Question 15

lectin pathway will activate ___

Answer 15

binds to carbs,

MASP-1 will activate itself and then activate MASP-2

MASP2 will convert C4 → C4a and C4b

C4b will bind to pathogen

lectin will convert C2 → C2b and C2a

C2a binds to C4b → convertase for C3

these two will convert C3 → C3a and C3b

C3b will bind to pathogen

Question 16

what convertase is used for C3

Answer 16

Question 17

lectin pathway generates the C3 convertase ___

Answer 17

C4bC2a

Question 18

lectin pathway simple

Answer 18

MASP-2 activated

C4 → C4b binds

C2 → C2a binds

C4bC2a converts C3→ C3a and C3b

C3b binds

Question 19

alternative pathway

Answer 19

C3 binds with H20 but doesnt break apart → iC3

inactive factor B binds to iC3

activated Factor D will bind and activate factor B → Bb and Ba creating iC3Bb

iC3Bb is a convertase (free floating) for C3

will convert C3 into C3a and C3b

Question 20

in the alternative pathway, ___ is a free floating convertase for C3

Answer 20

iC3Bb

Question 21

how is alternative pathway activated?

Answer 21

thioester bond inside C3 will be hydrolyzed by water forming iC3

Question 22

key between lectin and alternative pathway

Answer 22

lectin needs to bind to carb on pathogen surface to start process

where alternative just happens and it creates C3b that may or may not bind to near by pathogens (does not need to know pathogen is there, just constantly testing the plasma)

Question 23

___ is a system to constantly probe for pathogens

Answer 23

alternative pathway

doesn’t need to bind to pathogen to start pathway- just happens

attack first, regulate later

Question 24

amplification step of complement system

Answer 24

• Surface-bound C3b binds factors B then to factor D
• Forms C3 convertase C3bBb

•Amplification loop – each newly bound C3b can make another convertase by binding to its own B and D

•Fixes C3b on the pathogen surface which will eventually trigger complement effector mechanisms

Question 25

what binds to C3b in the amplification step

Answer 25

inactive B will bind to create C3bB then active D binds and actives B → Ba and Bb **creates C3bBb** which is a convertase for C3

Question 26

•Both the classical and lectin pathways also activate the alternative pathway convertase through \_\_\_

Answer 26

C3b.

Question 27

•alternative pathway components, like \_\_\_, will be activated by the classical and lectin pathways.

Answer 27

Factor B or Factor D

Question 28

three types of C3 convertases

Answer 28

C4bC2a → classical and lectin in first step C3bBb → used by alternative, classical and lectin during the amplification step iC3Bb→ used by alternative pathway in first step

Question 29

what C3 convertases are used by the lectin and classical pathway

Answer 29

* **C4bC2a** (pathogen surface) **activates** the cascade * **C3bBb** (pathogen surface) **amplifies** the response

Question 30

what C3 convertases are used to the alternative pathway

Answer 30

* **iC3Bb** (soluble) **activates** the cascade * **C3bBb** (pathogen surface) **amplifies** the response

Question 31

effector function of phagocytosis of the complement system

Answer 31

C3b binds to bacteria C3b is recongnized by CR1 receptors on phagocytic cells CR1 binds to C3b and eats cell then forms vesicle and breaks down pathogen

Question 32

•Pathogens opsonized by C3b are bound by phagocytic cells expressing \_\_\_

Answer 32

Complement Receptor 1 (CR1)

Question 33

C3b bond pathogen attached to CR1 on phagocytic cells will be endocytosed and killed when ___ fuse with phagosomes

Answer 33

lysosomes

Question 34

C\_\_\_ does not have thioester domain

Answer 34

C5

Question 35

how to activate C5 in the alternative pathway

Answer 35

**step 1 of forming Membrane Attack Complex** C3bBb will cleave C3→ C3b and C3a C3b will bind to C3bBb instead of pathogen surface creating **C3b₂Bb** **C3b₂Bb** will convert C5 → C5a and C5a

Question 36

how to activate C5 in the classical/lectin pathway

Answer 36

C4bC2a binds with a molecule of C3b C4bC2aC3b will convert C5→ C5a and C5b

Question 37

how to form MAC

Answer 37

1st step = C5 activation **C3b₂Bb**(alternative pathway) or **C4bC2aC3b** (classical/lectin) will convert C5→ C5a and C5b C5b binds with C6 and C7 C5bC6C7 binds to membrane and then binds to C8 this will cause binding and polymerization of C9 which will form a pore (MAC → membrane attack complex)

Question 38

how does C5b form a pore?

Answer 38

C5b binds with C6 and C7 C5bC6C7 binds to membrane and then binds to C8 this will cause binding and polymerization of C9 which will form a pore (MAC → membrane attack complex)

Question 39

MAC form ___ in the membrane

Answer 39

pores

Question 40

how does a prevent MAC on self

Answer 40

CD59 stops C9 from binding to C5b678

Question 41

what does CD59 do?

Answer 41

prevents C9 from binding to MAC and creating a pore

Question 42

what does C3b₂Bb do?

Answer 42

C5 → C5b and C5a (MAC → making pore) ## Footnote **alternative convertase**

Question 43

what does C4bC2aC3b do?

Answer 43

converts C5 → C5b and C5a (MAC → making pore) ## Footnote **classical and lectin pathway**

Question 44

what does C3a and C5a do?

Answer 44

**anaphylatoxins** increase the CR1 on phagoctyic cells (will bind to more C3 on pathogens) cytokine release degranulation chemotaxis MAST cells release histamine → increase vascular permeability

Question 45

what are anaphylotoxins?

Answer 45

C3a and C5a that go off and stimulate phagocytic cells to increase there function

Question 46

\_\_\_ is a much more potent chemoattractant but: ___ levels usually are much higher

Answer 46

C5a C3a (anaphylatoxin)

Question 47

how does complement pathway work?

Answer 47