Principles of Immunology
Complement
2/7/06
“Nothing is to be more prized than the value of each
day”
Goethe
Word List
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Complement fixation
Heat labile
Immune complexes
Opsonization
Proenzymes
History
 Bordet-Heat labile substance in the
serum
 Ehrlich-Named it complement
because it completes the action of
lysis when coupled with antibody
 Wasserman-Complement
fizxation(CF) test for syphilis
CF Test
Step 1-Mix unknown serum with Ag of known pathogen
Step 2-Add Complement
Step 3-Add Ab-coated RBCs to test system
Possible outcomes:
RBCs lyse
RBCs don’t lyse
Interpretation?
Effects of Complement
 Cell lysis
 Ab dependent
 Ab independent
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Opsonization
Inflammation
Clearance of Immune complexes
Viral neutralization
Complement Precursors
 ~ 5% of serum globulin
 Proenzymes (zymogens)-proteins or
glycoproteins
 Continuously circulate in inactive
state
 Source-hepatocytes, monocytes,
macrophages, epithelial cells
Complement Components
 C1 through C9
 Numbered in order of description, not
sequence of action
 Enzymatic reaction triggered by one
of three mechanisms
 Antibody-Antigen
 Microbial or non microbial foreign
substances
 Mannose binding lectin
Classical Pathway
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Adaptive immunity
C1 binds to Ag-Ab complex
Activated C1 cleaves C4 and C2
Formation of C3 convertase
C3 is cleaved
C5 is cleaved
Sequential binding of C6-C9
Alternative Pathway
 Innate immunity
 Spontaneous cleavage of C3 based on
multiple initiators
 Requires Factors B and D
 Formation of C3 convertase (less
stable)
 requires properdin
MB Lectin Pathway
 Innate immunity
 MB Lectin bound to microbial cell wall
components
 Follow-up binding of serine proteases
 This complex cleaves C4 and C2
much like activated C1
Biological Effects of C Activation
 Inflammation
 C3a, C5a
 Opsonization
 C3b
 Cell lysis
 Membrane attack complex (MAC) C5b-C9
Cell Receptors for C
 CR1
 Macrophages, neutrophils
 Binding of immune complexes
 CR3/CR4
 Macrophages, neutrophils
 Binding of immune complexes; enhanced
phagocytosis
Regulation of C
 Pre C3 convertase
 C1 inhibitor
 C4b binding protein
 Factor 1
 Post C3 convertase
 Factor H
 DAF
 At level of MAC
 S protein
 MIRL
C Deficiencies
 C3 deficiency
 Very severe
 Other deficiencies in C components or
inhibitors