Complement Flashcards

1
Q

functions of complement

A

lysis
opsonization
activation of inflammatory response
clearance of immune complexes

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

describe the classical pathway

A
  • Ab (IgM or 2 IgG) binds C1q
  • C1r C1s (2 of each) bind C1q - Ca2+
  • C4, C2 - C4bC2a (C3 convertase) - Mg 2+
  • C3 activated & C3b binds = amplification
  • C4bC2aC3b = C5 convertase
  • C5b678-C9 = MAC
  • split off products = C3a, C4a, C5a
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

describe the alternative pathway of complement

A
  • no Ab involved
  • spontaneous hydrolysis of C3
  • fluid phase (plasma) and cell bound
  • sialic acid on host cell inactivates C3b
  • proteins involved = factor B, D (serine protease), Properdin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

pathogen activators of alt pathway

A

gram neg = LIPOPOLYSACCH
gram pos = teichoic acid
fungi & yeast cell wall = zymosan
some viruses

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

non-pathogen activators of alt pathway

A

IgG, IgA, IgE
cobra venom
pur carbs (agarose, inulin)
anionic polymers = dextran sulphate

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

describe the lectin pathway

A
  • lectins acute phase reactants produced in liver = collectins
  • mannose-binding lectin (MBL)
    > mannose, N-acetyl glucosamine, D-glucose, L-fucose
  • proteins involved = MBL, MBL-associated serine proteases = MASP1, MASP2, MASP3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what happens in the lectin pathway?

A

MBL binds CHO residues on microbes
MASP binds and is activated
C4 C2 cleaved to C4BC2a
C3 activated

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

pathogens with D-mannose, L-fucose

A

gram neg = Salmonella
gram pos = Streptococci
yeast = C. albicans
viruses = influenza A, HIV
parasites = Leishmania

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

complement receptors

A

bind complement coated organisms to aid in clearance
- used in conjunction with regulator proteins (PROTECT HOST CELLS)
- amplify B cell signal
- used by some pathogens to enter cell

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

examples of complement receptors

A

CR1
CR2
CR3/4

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

CR1

A
  • aid phagocytosis by monocytes, macs, and neuts
  • binds C3b, C4b
  • help with immune complex clearance via rbc delivery to spleen
  • required for factor I to function
  • receptor for P. falciparum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CR2

A
  • co-receptor on B cell surface
  • amplification signalling with associated CD19 and CD81 (TAPA-1)
  • EBV uses CR2 as receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CR3 and CR4

A

CD11b/c/CD18 integrins
- aid phagocytosis by monos, macs, neuts
- help neuts and monos with extravasation
- present on NK cells

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

describe the three components of complement regulation

A
  • inhibitors regulate complement cascade = localize activation, protect host
  • soluble (plasma proteins)
  • membrane bound (host clls and some pathogens)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

list the soluble complement inhibitors

A

C1-inhibitor (C1-Inh)
factor H
factor I

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

describe C1-Inh

A

binds C1r2s2 and dissociates from C1q

17
Q

describe factor H

A
  • prevent binding of B to hydrolyzed C3 (C3H2O) and C3b
  • acts as a cofactor for factor I
18
Q

describe factor I

A
  • cleaves C3b into C3d + C3c
  • cleaves C4b into C4d + C4c
  • requires help = cofactor (CR1, factor H, CD46)
  • also called C3 inactivator
19
Q

membrane-bound complement inhibitors

A

DAF
MIRL

20
Q

describe DAF

A

decay-accelerating factor
- CD55
- inactivates C3 convertases

complement needs to bind in close proximity to CD55?

21
Q

describe MIRL

A

membrane inhibitor of reactive lysis
- CD59
- binds C5b678 preventing C9 insertion
- AKA protectin

22
Q

early complement deficiencies

A

C1q, C1r, C1s, C4, C2

23
Q

middle complement deficiencies

A

C3

24
Q

late complement deficiencies

A

C5, C6, C7, C8, C9

25
Q

SLE

A

systemic lupus erythematosus
- C1, C2, C4-def ppl at risk
- immune complexes not cleared
- build up in tissues (BM, vascular surfaces) = lead to tissue damage (neuts)

26
Q

C1-Inh deficiency

A
  • hereditary angioedema
  • localized edema = subcutaneous tissue, bowel, resp tract
  • autosomal dom
  • treat with C1-Inh or frozen plasma
27
Q

C1 esterase inhibitor

A

Berinert

27
Q

C1-Inh deficiency leads to _________ formation due to excess kallikrein

A

bradykinin

28
Q

factor I and H deficiencies

A

pts get recurrent infections

29
Q

CD55/CD59 deficiency

A
  • paroxysmal nocturnal hemoglobinuria
  • no PIG-A (phosphatidylinositol glycan A)
  • diagnosis = historical Hamm’s test; flow cytometry
  • anemia (susceptible to hemolysis), cytopenia, thrombosis
  • 10-15 yr survival without treatment => DVT
  • treatment = correct anemia, prevent thrombosis, BMT, Eculizumab (anti-C5)
30
Q

microbial evasion of complement (GPOS)

A

thick peptidoglycan prevents insertion of MAC
capsule provides physical barrier between C3b and CR2 = S. pneumoniae

31
Q

microbial evasion of complement (GNEG)

A

long polysaccharide chains prevent MAC insertion (E. coli and salmonella)

some N. gonorrhoeae have outer membrane protein that MAC will bind to = preventing insertion

P. aeruginosa has elastase which inhibits C3a and C5a

32
Q

protein mimicry by microbes

A

microbial membrane bound proteins similar to inhibitor proteins such as CR1, DAF, C1-Inh
- Vaccinia virus, Herpes, EBV, T. cruzi, C. albicans

33
Q

HIV evasion of complement

A
  • lipid envelope lysed by MAC
  • MBL can bind gp41 and 120 (no Abs)
  • helps neutralize Ab-coated viral particles = lyse HIV infected cells

BUT
- gp-41 and 120 on lipid envelope binds factor H
- virus incorporates host DAF and MIRL into membrane during budding
- complement coated virus gets picked up by CR1,3,4 = RBC transport virus, bind Mo, dendritic cells which interact with T lymphs, NK rich in CR4