Complement

Question 1

Complement System

Answer 1

• > 20 individual component system comprised of a series of inactive precursor molecules that when activated can be converted into active enzymes or effector molecules
• Produced in the liver + present in low levels in normal serum
• Part of innate immune system but is activated by adaptive

Question 2

Activation pathways

Answer 2

- 3 types:
\+ Classical pathway
\+ Alternative pathway
\+ Lectin Pathway
- All pathways converge at the point where C3 is cleaved

Question 3

Classical Pathway

Answer 3

• Involves Ab binding to antigen

- Dependent on adaptive immune response

Question 4

Alternative Pathway

Answer 4

• Complement triggered on contact with certain microbes

- Considered part of innate immune response

Question 5

Lectin Pathway

Answer 5

• Complement targeted by mannose-binding lectin sticking to mannose on surface of certain microbes
• Considered part of innate immune response

Question 6

Biological roles of complement (with relevant effector molecule)

Answer 6

• Opsonisation of microorganisms + immune complexes (C3b)
• Activation + attraction of phagocytes (C3a, C5a) - Has pro-inflammatory actions
• Degranulation of mast cell (C3a, C5a) - Has pro-inflammatory actions
• Lysis of target cells (C5b-C9 MAC)
• Chemotaxis

Question 7

MAC (Membrane-Attack Complex)

Answer 7

• Most commonly made from C5b, C6, C7, C8 + multiple C9 molecules
• Starting with at least 2 Fc regions binding simultaneously to 2 globular heads of C1q molecule, causing the molecule to become catalytically active + conformational changes
• Conformational change in C1q leads in activation + association of C1r + C1s which now become a catalytically active complex which then cleaves both C2 + C4 in to their respective fragments, which associate to generate C4b2a, which dimerise to form C3 convertase, later generates + dimerise to make C5 convertase (C4b2a3b)
• C5 convertase then split C5 into C5b + C5a, with them each going to perform different functions
• C5b will deposit on target surface to assemble MAC

Question 8

Opsonisation of microorganisms + immune complexes

Answer 8

C3b can act as an opsonin + is the primary complement component when activated by Ab

Question 9

Activation + attraction of phagocytes

Answer 9

• C3a, C4a + C5a can cause degranulation of mast cells to signal the immune cells to site of infection
• C3a + C5a are anaphylatoxins, meaning that they promote mast cell degranulation

Question 10

Complement deficiencies + diseases

Answer 10

• Includes:
  + Lacking early complement components C1, C2, C4
  + Lacking lytic MAC components C5 to C8
  + Lacking complement receptors in phagocytosis

Question 11

Infections in complement deficiencies

Answer 11

• C1r/q = Gram +tive respiratory infections
• C2 = Gram +tive recurrent respiratory, meningitis, sepsis, TB
• C3 = Gram +tive recurrent infections
• C4 = Gram +tive sepsis, meningitis
• C5 = Meningitis (N. meningitidis), disseminated gonococcal infection
• C6 = Meningitis (N. meningitidis), disseminated gonococcal infection
• C7 = Meningitis (N. meningitidis)
• C8 = Meningitis (N. meningitidis), disseminated gonococcal infection
  C9 = Meningitis (N. meningitidis)