COMPLEMENT SYSTEM  Recognition Unit

 C1 (with 3 subunits - C1q, r, s)

- a set of proteins that play a role in cytolytic particularly C1q binds to Ab
destruction of cellular antigens by specific  Stabilized by Ca++ (C1r, C1s remain
antibody. associated with C1q)
 Activation Unit
Inactivation of Serum  The formation of C5 convertase: C4, C2,
 removal of complement proteins C3
because they interfere in some  MAC (Membrane Attack Complex)
serological tests  C5-C9
 How?
1. Physical - 560C for 30 mins Note:
Freezed specimen - 560C for 10 mins  To activate 2 IgG (monomer) or 1 IgM
2. Chemical - Choline chloride (pentamer)
 Start of classical pathway  IMMUNE
Functions of the Complement System COMPLEX (Ag-Ab complex)
 Chemotaxins - C5a, C5b, C6, C7  Discovery - 12345678
 Immune adherence - C3b  Activation - 14235678
 Kinin Activator - C2b
 Anaphylatoxins - C3a, C4a, C5a (most C4a C2b
potent) C1  C4  C4b  C2  C2a  C4b2a (C3
 Opsonins - C3b, C4b, C5b convertase)  C3  C3b  C3 convertase =
 Virus neutralization - C4b, C1 C3a
C4b2a3b (C5 convertase)  C5678 (MAC) 
THREE PATHWAYS OF ACTIVATION C9 (FMAC - Final Membrane Attack Complex)
1. Classical Pathway
2. Alternative Pathway 2. Alternative Pathway
3. Lectin Pathway  aka By Pass/Properdin Pathway
 Properdin - stabilizes C5 convertase
C1q, r, s  bind by Ca++  IgG 2 & IgA
 Mg++ is important in this pathway
Notes:  Recognition Unit
*All proteins are synthesized in the liver  Triggers include
except IMMUNOGLOBULINS (synthesized by - bacterial cell walls (esp. with LPS)
the plasma cells) - fungal cell walls (zymosan)
*All complement proteins are synthesized in - yeast
the liver except C1 (produced by intestinal - viruses
epithelial cells) - virally infected cells
*Factor D  adipose tissue - tumor cell lines
*MASP - Mannose Binding Lectin Associated - some parasites (esp. Trypanosomes)
Serine Proteinase  Activation Unit
*Lectin - plant/animal extract  C5 convertase: C3bBbBb
 MAC
 C5-C9
1. Classical Pathway
 (C5 convertase)
C3a C3bBb(3b)(Bb)
C3  C3b  
Yeast  
Ba 
Factor D  Factor B  Bb 

3. Lectin Pathway
 starts with C4

Activating Substance Immune Complex LPS (bacterial Mannose Group on

capsules), IgA Microbial Cells
Recognition Unit C1q, C1r, C1s C3, Factor B, Factor D MBP, MASP-1
C3 Convertase C4b2a C3bBb C4b2a
C5 Convertase C4b2a3b C3bBb3b C4b2a3b
MAC C5b6789
End Result Cell lysis

Plasma Complement Regulation Deficiencies of Complement Components

 C1 inhibitor (C1 INH) dissociates C1r &
C1s from C1q
 Factor I - cleaves C3b and C4b C1 LE-like syndrome
 Factor H - competes for factor B C2
 C4 binding protein - acts as cofactor C3 LE-like syndrome, recurrent
with I to inactivate C4b infections
 S protein (vitronectin) - prevents C4 Severe recurrent infection
attachment of the C5b67 complex to C5
cell membrane C6 Neisseria Syndrome
 Decay Accelerating Factor (DAF) - C7
accelerates dissociation of C3 C8
convertase C9 No known disease
- associated with Cromer Blood Group C1 INH Hereditary Angioedema
System (HANE)
- Paroxysmal Nocturnal DAF & HRF PNH
Hemoglobinuria Factor H or I Recurrent bacterial infection

Inhibitors of MAC  C2 - most common factor deficiency

 HRF - Homologous Restriction Factor  C5 - aka Leiner’s disease
 CD 59 or MIRL (Membrane Inhibitor of
Reactive Lysis) Measurement of Complement Components
 CH50 Assay - amount of C’ serum serum
that can cause of hemolysis of the 50%
reagent RBC
 Radial Immunodiffusion (RID)
 Agar

 C3 - most abundant complement proteins

 C3b - most measured complement fragment

Clinical Significance:
 Elevated complement components have
little clinical importance
 Decreased complement components
Causes:
 Complement has been excessively
activated
 Complement is currently being
consumed
 Complement may be decreased or
absent due to genetic defect