Lecture 3 8/27/19

Question 1

what’s the most important component of the complement system

Answer 1

C3 is the most important.

Question 2

what is C3

Answer 2

when it is cleaved it gives two parts one is C3b that attaches to bacterium. and C3a recruits phagocytes

Question 3

what does C3b do

Answer 3

it binds the pathogen. because of that binding, the macrophages can eat the bacterium more efficiently than if it wasn’t coated in the complement

Question 4

alternative pathway

Answer 4

this is the first to act (first one to go against pathogen). started with C3 component. the pathogen surface creates local environment conductive to complement activation

Question 5

lectin pathway

Answer 5

second to act. mannose-binding lectin binds to pathogen surface

Question 6

classical pathway

Answer 6

third to act. C-reactive protein or antibody binds to specific antigen on pathogen surface

Question 7

what is the result of all 3 complement pathways

Answer 7

cleavage of C3 to C3a and C3b. C3b covalently bound to UNF

Question 8

what is iC3

Answer 8

this is created when a C3 is attacked by water. after this point everything happens closely to the surface of the pathogen membrane

Question 9

what happens to B factor once it beinds to iC3

Answer 9

it becomes succeptible to being cut by D factor. it is then cleaved into Bb + Ba

Question 10

what happens after B factor is cleaved

Answer 10

the Ba leaves and Bb continues on bound to iC3 making the soluble C3 convertase (iC3Bb)

Question 11

what happens once C3b is formed

Answer 11

it is bound to pathogen surface. it then binds B factor which is then cleaved by D factor (same as before) making the alternative C3 convertase (C3bBb)

Question 12

what does C3bBb do

Answer 12

it is able to bind another C3 making more C3b’s to bind to the membrane.

Question 13

what is the ultimate result of amplification of C3b pathway

Answer 13

the entire pathogen becomes coated with C3b (this happens very quickly) and as already stated this makes it much more easy for macrophages to phagocytose the pathogen

Question 14

what is properdin

Answer 14

it is a soluble plasma protein that stabilizes C3bBb and thus makes it easier for the convertase to make more C3b

Question 15

describe Factor H and factor I

Answer 15

they’re soluble plasma proteins. factor H makes C3b vulnerable to attack by factor I. this leaves an iC3b (not to be confused with iC3: inactive vs soluble C3)

Question 16

what is the purpose of H and I

Answer 16

they stop the replication process (allowing the bacterium to still be engulfed by the phagocytes)

Question 17

describe DAF

Answer 17

it is decay accelerating factor. it prevents the Bb molecule from binding to C3b stopping the replication process

Question 18

describe MCP

Answer 18

it is similar to factor H. it binds to C3bBb and makes it vulnerable to factor I attack

Question 19

describe process of phagocytes engulfing bacterium

Answer 19

complement activation leads to deposition of C3b on the bacterial surface. CR1 and macrophage binds to C3b on bacterium, endocytosis of the bacterium by the macrophage, macrophage membranes fuse, creating a membrane-bounded vesicle, the phagosome. lysosomes fuse with the phagosomes forming the phagolysosome

Question 20

why is alternative pathway the first one to act

Answer 20

because with have complement in our blood ready to go 24/7

Question 21

what two things can C3b

Answer 21

it can opsonize bacterium or continue with the alternative pathway

Question 22

describe C5 activation by the alternative C55 convertase

Answer 22

alternative C5 convertase (C3b2Bb) brings in C5 and cleaves it into C5b and C5a. C5b then goes on to form the Mb-attack complex (MAC)

Question 23

what is different from C3b to C5b

Answer 23

the thiel group is different and so it can’t bind hydroxyl group? it forms a structure that makes pores on the membrane of the pathogen

Question 24

what is CD59

Answer 24

it protects human cells by blocking polymerization of C9 factor. it bins to C5b678 and blocks the formation of the attack complex pore

Question 25

what are C3a and C3b

Answer 25

they're the small proteins that are cut from C3 and C5. they're anaphylatoxins, they can cause dangerous inflammation (anyphylaxis)

Question 26

what happens when C3a and C5a bind to monocytes and neutrophils in blood

Answer 26

it increases Adherence chemoattractant and CR1/CR3 expression. this leads to an increase in phagocytic activity

Question 27

what happens when C3a and C5a bind to mast cells

Answer 27

degranulation happens. histamine and vasoactive substances are made and increases capillary permeability UNF

Question 28

what are lectins

Answer 28

proteins that can bind carbohydrates

Question 29

describe the lectin pathway

Answer 29

when a macrophage makes contact with a bacterium it produces IL-6 which goes to the liver which produces C-reactive protein, fibrinogen, and mannose-binding lectin (MBL). these 3 are acute-phase proteins

Question 30

what does MBL do

Answer 30

it binds carbohydrates on the bacterial membrane. it can also opsonize the bacterium, or (similar to C3b) also continue activating the complement

Question 31

describe activation of C4 and C2 by the MASP proteins

Answer 31

activated by MASP-2 cleaves C4 to C4a and C4b. some C4b binds covalently to the microbial surface. activated MASP-2 lso cleaves C2 to C2a and C2b. C2a binds to surface C4b forming the classical C3 convertase (C4b2a). C4b2a binds C3 and cleaves it to C3a and C3b. C3b covalently to the microbial surface

Question 32

what initiates activation of C4 and C2

Answer 32

the mannose-binding lectin (MBL)

Question 33

compare C3 to C4

Answer 33

C3 is present at much higher concentrations in plasma than C4 so C3 contributes more to complement activation. C4 is analogous to C3 and C2 is analogous to factor B