Complement

Question 1

Complement components generate products that: (4 things)

Answer 1

1. Recruit inflammatory cells
2. opsonize microbial pathogens and immune complexes (facilitating antigen clearance)
3. Kill microbial pathogens
4. Generate an inflammatory response

Question 2

where does complement activation takes place

Answer 2

on antigenic surfaces (Antigen-Ab complexes, microbial surfaces, mammalian cell surfaces

Question 3

the three pathways of activation of complement

Answer 3

classical, lectin, and alternative

Question 4

Designation of components of the alternative pathway

Answer 4

Capital letters such as factor B, and factor D

Question 5

designation for the lectin pathway

Answer 5

acronyms such as MASP-2

Question 6

Classical pathway activation is initiated after

Answer 6

immune complex formation

Question 7

what does C1 bind to

Answer 7

A site on the Fc portion of an antibody that is exposed after it has bound to antigen

Question 8

C1 structure

Answer 8

macromolecule, of
Clq: 6 globular heads and extended tails
C1r
C1s

Question 9

what activates C1qrs

Answer 9

at least 2 of the C1q globular heads are simulaneously bound to antibody. This requires 2 Fc portions to be close together on the antigenic surface. (would need 2 antigens with IgG but only one on IgM due to its pentameric structure)

Question 10

C1r is activated by _____ and does _____

Answer 10

C1q binding to antigen; C1r cleaves C1s which activates C1s

Question 11

C1s becomes active after

Answer 11

it is cleaved from the C1qrs molecule by C1r

Question 12

Why does IgM require a smaller concentration to activate complement?

Answer 12

bc of its pentameric structure one IgM bound to antigen can bind to multiple of the globular heads of C1q

Question 13

The Lectin pathway is itiated by

Answer 13

a protein- Mannan Binding Lectine (MBL) or ficolis (which are homologous to C1q)

Question 14

MBL binds to

Answer 14

Mannose and other complex carbohydrates on the surface of many microbial pathogens

Question 15

Ficolins bind

Answer 15

oligosaccharides

Question 16

MASP- and MASP-2

Answer 16

Mannose binding lectin-associated serine protease: serine proteases that are physically associated with MBL/ficolins. similar to C1r and C1s

Question 17

MASP-1 and MASP-2 are activated by

Answer 17

MBL/ficolins binding to a surface and undergoing a conformational change

Question 18

difference between MBL and ficolins

Answer 18

similar structures but bind different carbohydrate domains
MBL-mannose and fructose residues
Ficolins- oligosaccharides w/ acetylated sugars

Question 19

acitivated C1qrs or activated MASP- and MASP-2 cleave

Answer 19

C4 to C4a and C4b

Question 20

C4b

Answer 20

binds to a cell surface (eg a microorganism) and the bound C4b binds C2

Question 21

C2 bound to C4b

Answer 21

C2 is cleaved by C1s forming the C4b2a complex which remains bound to the cell surface.

Question 22

C4b2a

Answer 22

cleaves C3 to C3a and C3b ( C3 convertase)

Question 23

major amplification step

Answer 23

C4b2a formation bc it can cleave up to 1000 molecules of C3

Question 24

C3b

Answer 24

binds to antigenic surfaces and is a power opsonin. enhances uptake of antigenic particle by phagocytes

Question 25

C5 covertase

Answer 25

aka: C4b2a3b. cleaves C5 into C5a and C5b

Question 26

C5a

Answer 26

soluble inflammatory mediator

Question 27

C5b

Answer 27

complexes with other complement components . its generation initiates the final phase of complemtn activation which is the formation of the Membrane Attact Comple (MAC)

Question 28

Alternative Pathway initiation

Answer 28

depends on slow, spontaneous hydrolysis of C3 in the cytoplasm. hydrolyzed C3 can bind factor B froming C3(H2O)Bb complex

Question 29

C3(H2O)Bb complex

Answer 29

C3 convertase that generates additional C3b

Question 30

C3b

Answer 30

is degraded rapidly or bound to a pathogenic surface

Question 31

Factor B is cleaved

Answer 31

after binding to C3b attached to a pathogenic surface, by Factor D. Forms- C3bBb

Question 32

C3bBb is stabilized by _____ and acts as ______

Answer 32

Factor P; C3 convertase. analogous to C4b2a of the classical pathway

Question 33

C3bBb + C3b =

Answer 33

C3bBbC3b which is a C5 covertase analogous to C4b2a3b of the classical pathway

Question 34

3 pathways converge at

Answer 34

the formation of a C5 covertase leading to the formation of a MAC complex

Question 35

MAC complex actions

Answer 35

creates a pore in the ell membrane and disrupts cell homeostasis by cellular lysis. can work on some viruses with a membrane coat too

Question 36

Opsonization

Answer 36

antigenic particles covered with C3b which is bound by CR1 (C3b receptors) and assist in the binding and ingestion of the particle by the phagocyte

Question 37

clearance of immune complexes

Answer 37

removal depends on C3b which bids to complement receptors on RBC which bring them to the spleen and liver where they are stripped off and destroyed by phagocytes

Question 38

inflammation is increased by

Answer 38

soluble fragments of complement C4a and C5a

Question 39

Chemotaxis

Answer 39

C5a attracts neutrophils, eosinophils, basophils, and monocytes via a C5 gradient

Question 40

vascular changes are caused by

Answer 40

C3a, C4a, and C5a via binding to receptos on mast cells and basophils which triggers granule release of histamine. Increase vascular permeability.

Question 41

anaphylatoxins

Answer 41

C3a, C4a, and C5a bc of their affects on vascular permeability.

Question 42

C1INH

Answer 42

C1 inhibitor- dissociates C1r and C1s from the complex

Question 43

What 5 things inhibit C3 covertase

Answer 43

``` Decay-accelerating factor (DAF) C4 binding protein (C4BP) Complement receptor 1 (CR1) Membrane cofactor protein (MCP) Factor I (I) ```

Question 44

what inhibits C5 covertase

Answer 44

``` Factor I (I) Factor H (H) Complement receptor 1 (CR1) ```

Question 45

CD59

Answer 45

prevents assembly of membrane attack complex

Question 46

Classical pathway deficiency

Answer 46

leads to immune complex disease

Question 47

lectin pathway deficiency

Answer 47

deficiency of MBL leads to bacterial infections maily in childhood (usually outgrown)

Question 48

Alternative pathway deficency

Answer 48

leads to infection with pyogenic bacteria and Neisseria spp. not no immune complex disease

Question 49

C3b defficiency

Answer 49

leads to infection with pyogenic bacteria and neisseria spp. sometimes immune-complex disease

Question 50

Membrane-attack component deficiencies

Answer 50

lead to infection with neisseria spp. only

Question 51

Hereditary angioneurotic edema

Answer 51

C1INH deficiency- failure to regulate C1 resulting in fluid accumulation, epiglottal swelling

Question 52

paroxysmal nocturnal hemoglobinurea

Answer 52

CD59 failure to function, lack of complement regulation leads to RBC lysis and blood in urine

Question 53

C8

Answer 53

binds the cell and interts into the membrane

Question 54

C9

Answer 54

forms the pore

Question 55

MAC works on what type of bacteria

Answer 55

gram negative