8 Complement

Question 1

Innate Immune response – recognition

Answer 1

Bacterial cell surface induces cleavage and complement activation
One complement fragment covalently binds to bacterium, other attracts an effector cell
Complement receptor on effector cell binds to complement fragment on bacterium
Effector cell engulfs bacterium, kills it and breaks down

Question 2

Stages of complement action

Answer 2

Pattern recognition trigger
Protease cascade amplification/C3 convertase
Inflammation, phagocytosis, membrane attack

Question 3

can complement kill

Answer 3

complement can directly kill through the membrane attack complex

Question 4

Complement pathways

Answer 4

antibody dependent

antibody independent

Question 5

Antibody dependent complement pathways

Answer 5

classical pathway

Question 6

Antibody independent complement pathways

Answer 6

lectin pathway and alternative pathway

Question 7

when is the lectin pathway activated

Answer 7

activated as soon as antigen in body – direct recognition of pathogen

Question 8

when is the alternative pathway activated

Answer 8

once complement is activated even more complement is activated

Question 9

when is the classical pathway activated

Answer 9

pathogen has to be recognised, producing antibodies

Question 10

what do the three pathways lead to

Answer 10

Three pathways all lead to activation of C3 and generation of C5 convertase
Activation of C5

Question 11

what happens in the classical pathway

Answer 11

antibodies bind to specific antigen on pathogen surface

Question 12

what happens in the lectin pathway

Answer 12

mannose-binding lectin binds to pathogen surface

Question 13

what happens in the alternative pathway

Answer 13

pathogen surface creates local environment conductive to complement activation

Question 14

what does the C3 molecule lead to

Answer 14

All lead to C3 molecule – which in the end leads to the membrane attack complex

Question 15

Physiological consequences of complement activation

Answer 15

Bacteria = lysis
Phagocyte = chemotaxis
Bacteria = opsonization

Question 16

what is lysis

Answer 16

forming holes in membrane – membrane attack complex

Question 17

what is opsonization

Answer 17

tagging of pathogen to see something foreign in the body

Question 18

Components of lectin pathway

Answer 18

Mannose groups
Mannose Binding Lectin
C4
C2

Question 19

what are the enzymes in the lectin pathway

Answer 19

Enzymes: MASP2 and MASP1

serine proteases

Question 20

what do the enzymes in the lectin pathway do

Answer 20

switch on the process when activated

Question 21

what activates the enzymes in the lectin pathway

Answer 21

When mannose bind lectin binds to the mannose groups on surface = activation of MASP1 and MASP

Question 22

what does MASP1 do

Answer 22

activates MASP2

Question 23

what does MASP2 do

Answer 23

cleaves C4 into C4a and C4b

Question 24

how is C3 convertase made in the lectin pathway

Answer 24

C2 cleaved into C2a and C2b

C2a joins onto pathogen surface with C4a = C3 convertase

Question 25

how is a C5 convertase generated in lectin pathway

Answer 25

one molecule of C4b2a can cleave C3 to C3b, C3b bind to microbial surface (deposition on pathogen surface) C4b2a3b = C5 C5 convertase leads to membrane attack complex

Question 26

Components of classical pathway

Answer 26

C1, C2, C3, C4

Question 27

what is C1 complex

Answer 27

made of C1q and C1r and C1s (serine proteases C1r and C1s – to activate need to be bound to two IgG or IgM = conformational change)

Question 28

how is the classical pathway initiated

Answer 28

Pentameric IgM molecule binds to antigens on bacterial surface and adopts ‘staple’ form C1 binds to single IgM molecule IgG molecules bind to antigens on bacterial surface C1q binds to two or more IgG molecules

Question 29

how is a C3 convertase generated in classical pathway

Answer 29

Activated C1s cleaves C4 to C4a and C4b. some C4b binds covalently to microbial surface Activated C1s also cleaves C2 to C2a and C2b

Question 30

how is a C5 convertase generated in the classical binding pathway

Answer 30

C2a binds to surface C4b forming classical C3 convertase, C4b2a

Question 31

what does the C4b2a do in the classical pathway

Answer 31

binds C3 and cleaves C3a into C3b

Question 32

what does C3a do

Answer 32

causes inflammation, mast cells to degranulate

Question 33

what does the C3b made in the classical pathway do

Answer 33

binds covalently to microbial surface

Question 34

Components of the alternative pathway

Answer 34

C3b factor b factor d properdin

Question 35

what does factor b do in the alternative pathway

Answer 35

binds to C3b makes alternative pathway C3b

Question 36

what does factor d do in the alternative pathway

Answer 36

plasma serine protease, cleave B when it is bound to C3b to Ba and Bb

Question 37

how is C3 generated in alternative pathway

Answer 37

C3bBb = C3 convertase of alternative pathway C3b deposited by classical or lectin pathway C3 converase C3b binds to factor B = C3bB Bound factor B is cleaved by plasma protease factor D into Ba and Bb C3bBb complex is C3 convertase, cleaving many C3 molecules to C3a and C3b

Question 38

what is C3a needed for

Answer 38

mast cell activation

Question 39

what is C3b needed for

Answer 39

C3b to get more C3a

Question 40

C5 function in the membrane attack complex

Answer 40

on activation the soluble C4b initiates assembly of MAC in solution

Question 41

C6 function in the membrane attack complex

Answer 41

binds to and stabilises C5b, forming C7 binding site

Question 42

C7 function in the membrane attack complex

Answer 42

binds to C5b, 6 and exposes a hydrophobic region that permits attachment to cell membrane

Question 43

C8 function in the membrane attack complex

Answer 43

binds to C5b, 6, 7 and exposes a hydrophobic region that inserts into cell

Question 44

C9 function in the membrane attack complex

Answer 44

polymerization on C5b, 6, 7, 8 complex, form membrane-spanning channel that disrupts cell’s integrity and can cause cell death

Question 45

what does opsonization and phagocytosis do

Answer 45

C3b and C4b of complement binds tagging for phagocytosis

Question 46

Cellular recruitment and activation

Answer 46

Increased vascular permeability Vasodilation C5a and C3a activates mast cell= cellular recruitment and inflammation Chemo-attractive properties = chemotaxis

Question 47

what leads to inflammation

Answer 47

C3a and C5a

Question 48

what do mast cells lead to

Answer 48

C3a, C5a, PAMPs damage

Question 49

what are the complement functions

Answer 49

host benefit | host detriment

Question 50

complement - Host benefit

Answer 50

- opsonization to enhance phagocytosis - phagocyte attraction and activation - lysis of bacteria and infected cells - regulation of antibody responses - clearance of immune complexes - clearance of apoptotic cells

Question 51

complement - Host detriment

Answer 51

- inflammation (through C3a/C5a and mast cells) | - anaphylaxis