Complement factor I (not C1) deficiency

• patients of either sex with multiple hospital admissions starting in early childhood for bacterial infections caused by several different organisms

• tendency to get hives

• RBC coated with C3b

• normal Ig levels and antibody response to immunizations

• normal delayed hypersensitivity reaction

• low serum C3 because it is being consumed

  • low or absent B and I

Principles to understand

• C3 tickover produces C3a and C3b spontaneously and at a very low rate

• if no bacteria are around, C3b is immediately inactivated

• C3bBb is a C3 convertase (C3ase), part of the alternate pathway; recall that C2b4b is also a C3 convertase

• H + I + C3b yield iC3b, which is no longer an enzyme but is one of the best opsonins; so, if you lack I, C3 will be consumed rapidly but will not opsonize bacteria, leading to infections

• C3a degranulates mast cells, resulting in hives

C3b and B ultimately form a C3 convertase

• C3b on microbial surfaces binds factor B

• bound actor B is cleaved by plasma protease factor D into Ba and Bb

  • by the way, the suffix –a means it floats AWAY, as in C4a

  • –b means it BINDS, as in C3b

• C3bBb complex is a C3 convertase, which converts more C3 into C3a and C3b

• however, H can displace B, enabling factor I to cleave C3b into iC3b, which, as we discussed earlier, is an opsonin. it is an inactive as an enzyme, but it is an active opsonin ppt 14

• if factor I is missing, C3 is cleaved into C3b but nothing cleaves it into iC3b. therefore, no opsonization occurs

Opsonization

• bacteria is coated with complement iC3b

• when iC3b binds to CR3, bacteria are phagocytosed

• note that if iC3b is not working, you can still opsonize a little bit because macrophages have Fc receptors

• but iC3b is still a much better opsonin than antibodies, so without iC3b, opsonization is very much hindered

Decay of plasma C3 levels in patients with factor I deficiency

• C3 level in normal subjects doesn’t decline that quickly

• C3 level in I-deficient patients decreases rapidly

• if you infuse the I-deficient patient with plasma, C3 level no longer falls quite so quickly

Category: Pathology Notes