Lecture 26 - Complement Proteins II

Question 1

Complement components that act as opsonins

Answer 1

C3b, C4b

Question 2

Complement receptors involved in phagocytosis

Answer 2

CR1, CR3

Question 3

Another name for CR1

Answer 3

CD35

Question 4

Another name for CR3

Answer 4

Mac-1

CD11bCD18

Question 5

Cells that express CR1 and CR3
1)
2)
3)
4)

Answer 5

1) Macrophages
2) Neutrophils
3) Follicular dendritic cells
4) Erythrocytes

Question 6

What do CR1 and CR3 have a high affinity for?

Answer 6

C3b, iC3b, C4b

Question 7

What does CR3 bind?

Answer 7

iC3b

Question 8

iC3b

Answer 8

Breakdown product of C3b that forms on cell membranes

inactive C3b

Question 9

What enhances C3b phagocytosis?

Answer 9

Specific IgG also binding to microbe

Question 10

Role of CR1 on erythrocytes

Answer 10

Binds to C3b/C4b opsonised microbes, transports them to the spleen, where they are destroyed
Erythrocyte is not destroyed in this process.

Question 11

CR2
1)
2)
3)
4)

Answer 11

1) CD21
2) Complement receptor on B cells
3) Complexes with CD19 and CD81
4) Provides a second signal for B cell activation

Question 12

Which cells express CR2?

Answer 12

B cells

Follicular dendritic cells

Question 13

What does CR2 bind?

Answer 13

iC3b, C3dg antigen/antibody complexes

Question 14

What is C3dg?

Answer 14

A C3 breakdown product

Question 15

CR4
1)
2)
3)

Answer 15

1) Dimer of CD11c and CD18
2) Present on dendritic cells
3) Similar function to CR3

Question 16

Role of complement in B cell activation
1)
2)
3)

Answer 16

1) Antigens coated by C3dg bind IgM and CR2
2) Boosts phosphorylation of ITAM residues on Igalpha and Igbeta
3) This amplifies BCR signalling

Question 17

Which complement components are anaphylatoxins?

Answer 17

C3a, C5a

Question 18

Effects of C3a and C5a

Answer 18

Anaphylatoxins

Cause systemic inflammation, which in extreme cases resembles anaphylactic shock

Question 19

Where are C3a and C5a receptors found?
1)
2)
3)

Answer 19

1) Mast cells
2) Endothelial cells
3) Phagocytes

Question 20

How do C3a and C5a cause systemic inflammation?
1)
2)
3)

Answer 20

1) Bind to mast cells, cause them to release TNFa, histamine
2) Bind to endothelial cells, induce vascular leakage
3) C5a is a chemotactant. Attract neutrophils, monocytes

Question 21

C3aR and C5aR structure

Answer 21

Seven-pass transmembrane proteins

GPCR

Question 22

Agents targeted by the complement cascade

Answer 22

Extracellular bacteria, free virions, parasites

Question 23

Bacterial factors that activate C’

Answer 23

Peptidoglycan and LPS activate the alternative pathway

Question 24

Results of activation of C'
1)
2)
3)
4)
5)

Answer 24

1) Direct lysis
2) Inflammation
3) Chemotaxis
4) B cell activation
5) Opsonisation

Question 25

DAF, CR1, MCP roles

Answer 25

Regulate C3 convertase production | Membrane-bound

Question 26

Factor I and factor H roles

Answer 26

Cleave C3b (to inactivate)

Question 27

CD59 role

Answer 27

Inhibit MAC formation

Question 28

Self cells susceptible to C' lysis

Answer 28

Erythrocytes | Have low levels of regulatory proteins on surface

Question 29

How can C3 convertase be inhibited? 1) 2)

Answer 29

1) Classical pathway DAF, CR1, MCP bind to C4b, displace C2a from C3 convertase 2) Alternative pathway DAF, CR1 bind to C3b, displace Bb from C3 convertase complex

Question 30

DAF 1) 2) 3)

Answer 30

1) Decay accelerating factor 2) Membrane-bound 3) Bind to C4b or C3b, displace C2a or Bb from C3 convertase

Question 31

``` MCP 1) 2) 3) 4) ```

Answer 31

1) Membrane cofactor protein 2) Membrane-bound 3) Bind to C4b, displace C2a from C3 convertase 4) Can also act as a cofactor for factor I cleaving membrane-bound C3b

Question 32

CR1 roles 1) 2) 3)

Answer 32

1) Bind C3b, C4b when these act as opsonins 2) Break down C3 convertase complex by displacing either C2a from C4b, or Bb from C3a 3) Can act as a cofactor for factor I cleaving membrane-bound C3b

Question 33

Factor I 1) 2) 3) a,b

Answer 33

1) Serine protease 2) Inactivates fluid-phase C3b 3) Requires additional cofactors to cleave cell-membrane-bound C3b a) Factor H b) MCP or CR1

Question 34

Factor H 1) 2)

Answer 34

1) Cofactor for factor I cleavage of cell-membrane-bound C3b | 2) Binds to sialic acid, which is highly expressed on mammalian cells.

Question 35

Products of factor I cleavage of C3b

Answer 35

iC3b, C3d, C3dg (which bind CR on B cells and phagocytes)

Question 36

CD59 1) 2)

Answer 36

1) Cell-membrane-bound protein | 2) Binds to C5a on C5b/C6/C7/C8 complex, inhibits C9 from forming pore

Question 37

Effect of C' on immune complexes

Answer 37

Promotes solubilisation of antibody-antigen complexes

Question 38

What determines the ABO blood groups?

Answer 38

Allelic difference in enzymes that modify glycans on cell surfaces

Question 39

A allele in blood groups

Answer 39

Encodes enzyme that transfers an N-terminal acetylgalatosamine onto glycans

Question 40

B allele in blood groups

Answer 40

Encodes an enzyme that transfers a terminal galactose residue onto glycans

Question 41

O allele in blood groups

Answer 41

Doesn't encode an enzyme to modify cell-surface glycans

Question 42

Immune component enforcing blood groups

Answer 42

Natural IgM produced against missing allele

Question 43

Classical pathway deficiencies

Answer 43

Missing C1, C2, C4 | Leads to immune complex disease (EG: systemic lupus erythematosus)

Question 44

Alternative pathway deficiencies

Answer 44

Missing B, D, properdin | Increased risk of disease from Neisseria gonorrhoeae or meningitidis

Question 45

Alternative and classical pathway deficiencies

Answer 45

Deficiencies in C3 or factors I or H | Increased infections with Strep pneumoniae, Neisseria spp, Haemophilus influenzae

Question 46

What do deficiencies in factors I and H do?

Answer 46

Mimic C3 deficiencies

Question 47

How can microbes evade C'? 1) 2) 3)

Answer 47

1) Recruit host C' regulatory proteins 2) Mimic human C' proteins 3) Inhibit C'-mediated inflammation

Question 48

How do microbes recruit host C' regulatory proteins? 1) 2) 3)

Answer 48

1) Express or scavenge sialic acid (this recruits factor H) 2) Synthesise or recruit factor H (EG: gp41 of HIV) 3) Viruses incorporate host regulatory proteins into envelope when budding (EG: HIV recruits DAF, CD59)

Question 49

Microbe that mimics human C' proteins

Answer 49

E coli has a C1q binding protein

Question 50

Microbe that inhibits C'-mediated inflammation

Answer 50

Staph aureus, using CHIPS (chemotaxis inhibitory protein of Staph aureus)

Question 51

When do C' deficiencies normally present?

Answer 51

~6-9 months after birth