The complement system consists of over 30 proteins produced by the liver and found in circulating blood serum. It works as a cascade system where one reaction triggers another rapidly. The complement system plays a critical role in inflammation and defense against some bacterial infections, and may be activated during blood transfusions or autoimmune diseases. There are three complement activation pathways: the classical pathway which is initiated by antigen-antibody complexes, the alternative pathway which can be triggered by pathogens, and the lectin pathway which is initiated when mannose-binding lectin binds to carbohydrates on bacteria. All three pathways converge to form the membrane attack complex, which creates pores in the pathogen's membrane leading to cell death.

1. Complement system
Dr Hassan Yar

2. The complement system
• A defensive system consisting of over 30 proteins produced by the
liver and found in circulating blood serum.
• These proteins are not immunoglobulins and their concentrations in
serum do not increase after immunization
• Complement activation (fixation) leads to lysis of cells and to the
generation of many powerful biologically active substances

3. Cascade
• The complement works as a cascade system:
Cascade is when one reaction triggers another reaction which trigger others
and so on. These types of systems can grow exponentially very fast.

4. Role of Complement in Disease
• The complement system plays a critical role in inflammation and
defense against some bacterial infections.
• Complement may also be activated during reactions against
incompatible blood transfusions, and during the damaging immune
responses that accompany autoimmune disease.
• Deficiencies of individual complement components or inhibitors of
the system can lead to a variety of diseases

5. Cascade Activation
• Complement proteins are often designated by an uppercase letter C
and are inactive until they are split into products.
Example: C1
• When the products are split they become active. The active products
are usually designated with a lower case a or b.
Example: C1a and C1b

6. Functions
• Four Important functions:
1. Lysis
2. Opsonization
3. Activation of inflammatory response
4. Clearance of immune complexes

12. Complement Activation Pathways
• Ag-Ab complexes
The Classical
Pathway
• Aggregated Ig and microbial products
The Alternate
Pathway
• Microbial Products
Mannan-binding
Lecithin Pathway

14. The Classical Pathway
• Activators: Ag – Ab complexes
• Antibodies involved: IgG and IgM
• Activation in an orderly fashion of nine major protein components; C1
– C9
• Products of activation are enzymes that catalyze the subsequent step

15. Classical pathway 142-356789
• The classical pathway is considered to be part of the specific immune
response because it relies on antibodies to initiate it.
• C1 becomes activated when it binds to the ends of antibodies

16. Alternative Pathway
• Four components: C3, factor B, factor D, and properdin
• Triggering substances may be pathogens or Nonpathogens; bacterial
cell wall components, fungi, viruses, parasites immune complexes,
RBCs, polymers

18. Lectin Pathway
• Lectin is a protein that binds to carbohydrate
• MBL (mannose-binding lectin) binds to mannose on many bacterial
cells MBL is produced by liver in acute-phase inflammatory reactions
• Once MBL binds to target cell, 2 serine proteases (MASP-1, MASP-2)
bind Acts like C1

20. Finally what do these pathways do?
• Converge to form membrane attack complex (MAC)
• MAC forms large channel through the membrane of pathogen
• Because of the open channel ions move freely in & out!
• Cell cannot maintain osmotic stability
• Killed by
• Influx of water
• Loss of electrolytes

21. Where is it synthesized?
• C1: Intestinal epithelium
• C2: Macrophages
• C3: Liver
• C4: Macrophages
• C5: Spleen
• C6: Liver
• C8: Spleen
• C9: Liver
• C4, C5, C6 & C3 are Acute phase reactants

22. Consequences of Complement Deficiency

23. The End