The Complement Components & Diseases

A comprehensive guide for medical professionals and students

Classical Pathway Components

C1 Complex (C1q, C1r, C1s)

Function:

• C1q: Recognition and binding to antibody-antigen complexes
• C1r: Autoactivation following C1q binding
• C1s: Cleaves C4 and C2

Associated Diseases:

• C1q deficiency: Systemic Lupus Erythematosus (SLE)
• Hereditary angioedema (C1-INH deficiency)
• C1q nephropathy

C4 (C4a, C4b)

Function:

• C4b: Forms C3 convertase with C2a
• C4a: Anaphylatoxin (weak)

Associated Diseases:

• C4 deficiency: SLE
• Autoimmune diseases
• Recurrent bacterial infections

C2 (C2a, C2b)

Function:

• C2a: Forms C3 convertase with C4b
• C2b: No known function

Associated Diseases:

• C2 deficiency: SLE
• Recurrent pyogenic infections
• Vasculitis

Alternative Pathway Components

Factor B

Function:

• Forms alternative pathway C3 convertase with C3b
• Amplification loop component

Associated Diseases:

• Factor B deficiency: Recurrent bacterial infections
• Neisseria infections

Factor D

Function:

• Cleaves Factor B when bound to C3b
• Rate-limiting enzyme of alternative pathway

Associated Diseases:

• Factor D deficiency: Increased susceptibility to infections
• Associated with some forms of hemolytic uremic syndrome

Properdin (Factor P)

Function:

• Stabilizes alternative pathway C3 convertase
• Pattern recognition molecule

Associated Diseases:

• Properdin deficiency: Fulminant meningococcal disease
• Increased susceptibility to Neisseria infections

Terminal Pathway Components

C3 (C3a, C3b)

Function:

• C3b: Opsonization, forms C5 convertase
• C3a: Anaphylatoxin, inflammation

Associated Diseases:

• C3 deficiency: Recurrent bacterial infections
• Membranoproliferative glomerulonephritis
• Age-related macular degeneration

C5 (C5a, C5b)

Function:

• C5a: Most potent anaphylatoxin
• C5b: Initiates membrane attack complex formation

Associated Diseases:

• C5 deficiency: Neisserial infections
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Atypical hemolytic uremic syndrome

C6-C9 (Membrane Attack Complex)

Function:

• Form the membrane attack complex (MAC)
• Creates pores in cell membranes
• Leads to cell lysis

Associated Diseases:

• C6-C9 deficiencies: Recurrent Neisseria infections
• Systemic lupus erythematosus
• Neuromyelitis optica

Regulatory Proteins

Factor H

Function:

• Regulates alternative pathway
• Accelerates decay of C3 convertase
• Acts as cofactor for Factor I

Associated Diseases:

• Factor H deficiency: Atypical hemolytic uremic syndrome
• Age-related macular degeneration
• C3 glomerulopathy

Factor I

Function:

• Cleaves and inactivates C3b and C4b
• Regulates both classical and alternative pathways

Associated Diseases:

• Factor I deficiency: Recurrent bacterial infections
• Atypical hemolytic uremic syndrome
• Age-related macular degeneration

CD55 (DAF) and CD59

Function:

• CD55: Accelerates decay of C3/C5 convertases
• CD59: Prevents MAC formation

Associated Diseases:

• Deficiency: Paroxysmal nocturnal hemoglobinuria
• CHAPLE syndrome (CD55 deficiency)