Download Complement Components are produced by: Liver hepatocytes

The Complement System
Dr. M. Izad
Oct 2009
Objectives

To understand how the complement system works

To determine the Role of Complement in the Innate
& Acquired Immunity

Regulation of complement system

To understand the consequences of Deficiency of
Complement
History
 Jules
Bordet 1890s
 Lysis of bacteria (Vibrio Cholerae)
 Hemolysis
 Paul
Ehrlich
Complement “The activity of blood serum
that completes the action of antibody”
Complement ( C )
 Complement consists of a complex series of over 30
soluble & cell-bound Proteins. Many of which are
enzymes (proenzyme/zymogen-proteinases).
The biological activities of this system affect both
innate & acquired immunity.
They can bind to an antibody molecule or can act
independently, to affect various aspects of the immune
system.
Complement Components are
produced by:
 Liver hepatocytes
 Macrophages
 Blood monocytes
 Epitelial cells of gastrointestinal &
genitourinary tracts
•Complement components are
designated by:
•Neumerals (C1-C9)
•Letter symbols (e.g., factor D)
•Trivial names (e.g., homologus
restriction factor)
•The
smaller
fragment
resulting fromcleavage of a
component is designated “a”
&
the
larger
fragment
designated “b”
•Those complexes that have
enzymatic
activation
are
designated by a bar over the
number or symbol (e.g., C 4b2a
Complement Activation
C1 Structure
Figure 2-53 part 3 of 3
Innocent bystander lysis
Figure 2-35
•Bacteria (Salmonella, Listeria,
Nisseria)
•Fungi (Cryptococcus Neoformans,
Candida Albicans
•Viruses ( HIV)
Figure 2-24
Regulation of the Complement
system
Classical Pathway
C1 inhibitor
Classical & Lectin Pathways
C4bBp, CR1, MCP
CR1, MCP
Alternative Pathway
Factor H, CR1, MCP
CR1,MCP,
Classical & Lectin & Alternative
Pathways
DAF (CD55)
C4bBp, CR1,
Factor H
C3bBb
C3b
Regulation at assembly of MAC
S protein
Regulation at assembly of MAC
Homologous restriction factor(HFR) or CD59
/CD59
Functions of Complement
Complement Receptors
Deficiency of Complement System
Classical Pathway
• C1q,
C1r,
C4,C2
•C1q,
C1r,
C1s,C1s,
C4,C2
homozygous
homozygous
deficiencies
deficiencies
• Immune Complex Disease
such as systemic lupus
erythematosus,
vasculitis,
glomerulonephritis
• Recurrent
infections
by
pyogenic bacteria such as
streptococci & staphylococci
Alternative Pathway
• Factor D & properdin deficiencies
Neisseria Infection
Classical & Alternative Pathways
C3 dificiency
• Homozygous
deficiencies in
components
involved in the
MAC formation
• Immune Complex
Disease
• Recurrent Bacterial
infections
Congenital Deficiency of
Complement Regulatory
Proteins
• C1 inhibitor deficiency
Hereditary angioedema
• DAF & CD59 deficiency
Paroxymal nocturnal hemoglobinuria