Complement Flashcards

1
Q

Complement components generate products that: (4 things)

A
  1. Recruit inflammatory cells
  2. opsonize microbial pathogens and immune complexes (facilitating antigen clearance)
  3. Kill microbial pathogens
  4. Generate an inflammatory response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

where does complement activation takes place

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

the three pathways of activation of complement

A

classical, lectin, and alternative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Designation of components of the alternative pathway

A

Capital letters such as factor B, and factor D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

designation for the lectin pathway

A

acronyms such as MASP-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Classical pathway activation is initiated after

A

immune complex formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what does C1 bind to

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

C1 structure

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what activates C1qrs

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

C1r is activated by _____ and does _____

A

C1q binding to antigen; C1r cleaves C1s which activates C1s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

C1s becomes active after

A

it is cleaved from the C1qrs molecule by C1r

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why does IgM require a smaller concentration to activate complement?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

The Lectin pathway is itiated by

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

MBL binds to

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Ficolins bind

A

oligosaccharides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

MASP- and MASP-2

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

MASP-1 and MASP-2 are activated by

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

difference between MBL and ficolins

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

acitivated C1qrs or activated MASP- and MASP-2 cleave

A

C4 to C4a and C4b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

C4b

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

C2 bound to C4b

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

C4b2a

A

cleaves C3 to C3a and C3b ( C3 convertase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

major amplification step

A

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

24
Q

C3b

A

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

25
Q

C5 covertase

A

aka: C4b2a3b. cleaves C5 into C5a and C5b

26
Q

C5a

A

soluble inflammatory mediator

27
Q

C5b

A

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

28
Q

Alternative Pathway initiation

A

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

29
Q

C3(H2O)Bb complex

A

C3 convertase that generates additional C3b

30
Q

C3b

A

is degraded rapidly or bound to a pathogenic surface

31
Q

Factor B is cleaved

A

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

32
Q

C3bBb is stabilized by _____ and acts as ______

A

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

33
Q

C3bBb + C3b =

A

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

34
Q

3 pathways converge at

A

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

35
Q

MAC complex actions

A

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

36
Q

Opsonization

A

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

37
Q

clearance of immune complexes

A

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

38
Q

inflammation is increased by

A

soluble fragments of complement C4a and C5a

39
Q

Chemotaxis

A

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

40
Q

vascular changes are caused by

A

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

41
Q

anaphylatoxins

A

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

42
Q

C1INH

A

C1 inhibitor- dissociates C1r and C1s from the complex

43
Q

What 5 things inhibit C3 covertase

A
Decay-accelerating factor (DAF)
C4 binding protein (C4BP)
Complement receptor 1 (CR1)
Membrane cofactor protein (MCP)
Factor I (I)
44
Q

what inhibits C5 covertase

A
Factor I (I)
Factor H (H)
Complement receptor 1 (CR1)
45
Q

CD59

A

prevents assembly of membrane attack complex

46
Q

Classical pathway deficiency

A

leads to immune complex disease

47
Q

lectin pathway deficiency

A

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

48
Q

Alternative pathway deficency

A

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

49
Q

C3b defficiency

A

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

50
Q

Membrane-attack component deficiencies

A

lead to infection with neisseria spp. only

51
Q

Hereditary angioneurotic edema

A

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

52
Q

paroxysmal nocturnal hemoglobinurea

A

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

53
Q

C8

A

binds the cell and interts into the membrane

54
Q

C9

A

forms the pore

55
Q

MAC works on what type of bacteria

A

gram negative