The complement system consists of 30 serum proteins that are produced as inactive zymogens and activated in a cascade manner. When activated, complement proteins become proteases that activate other complement components. There are three complement activation pathways: the classical, lectin, and alternative pathways. Activation leads to formation of the membrane attack complex that forms pores on cell membranes, lysing cells. Complement proteins also have roles in opsonization, inflammation, and immune clearance. Bacteria have developed mechanisms to evade complement-mediated lysis like inhibiting membrane attack complex insertion or degrading anaphylatoxins. Deficiencies of specific complement components are associated with increased risk of certain infections or autoimmune diseases.

1. Complement system
Dr. Mahendra Swamy
MBBS, MD(Microbiology)

2. - Introduction
- Complement components
- General properties
- Complement cascade/pathway
- Biological effects
- Evasion of Complement system
- Complement deficiencies

3. Introduction
• The term "complement" was coined by Paul
Ehrlich.
• Complements complement the action of
Antibodies.
• They are group of proteins present in plasma.
• They constitute 5% of overall plasma proteins.
• They are present in inactive form.
• Activated by antigen-antibody reaction.

4. • During activation, some complement components
are split into two parts.
• The larger part of the molecule called "b" while the
smaller fragment called "a" may diffuse away.
• In most cases it is the "b" fragment binds to the
surface of the cell to be lysed.
• Activation of complement results in the production
of several biologically active molecules, which
contribute to nonspecific immunity and
inflammation.
• Their levels are estimated in unexplained
inflammation/edema, autoimmune diseases.

5. Complement components
• Consist of 30 distinct serum proteins.
• Produced by hepatocytes, macrophages and
intestinal epithelial cells.
• Complement proteins are zymogens
(proenzymes). When activated, they become
proteases & activate other complement proteins.
• Reaction goes on in a cascade manner.
• Their levels do not increase following infection.

6. General properties
• Their levels do not increase following
infection/immunization.
• They are heat labile.
• They cause lysis of cells (Cytolysis)
• They bind only to the immune-complexes & not
to free antibodies.
• They are species nonspecific.
• They bind to the Fc portion of antibodies.

7. Complement cascade/pathway
• Three pathways:
• Classical pathway: Antibody dependent pathway:
Triggered by Immune complexes. It involves all
components from C1 to C9.
• Alternate pathway: Antibody independent pathway:
Triggered by Antigen alone. Initiators of Alternate
pathway are: Lipopolysaccharide from gram negative
bacilli, fungal cells, virus infected cells, tumor cells,
cobra venom factor etc. It involves all components
except C1, C2 & C4. It involves two other important
factors like factor B & factor D.

8. • Lectin pathway: Antibody independent pathway.
It is mediated through interaction of lectin
proteins of host with mannose residue present on
microbial surface. It involves all components
except C1.
• Stages of complement activation:
• Initiation of pathway
• Formation of C3 convertase
• Formation of C5 convertase
• Formation of Membrane attack complex (MAC)

10. • C3a, C4a, C5a are Anaphylatoxins
• C5b-C9 complex is Membrane attack complex
(MAC)
• MAC- Forms pores on the cell membranes of
organisms leading to free passage of ions &
water into cell, thus there is cell swelling & cell
lysis.

11. Biological effects/Functions of
Complements
1. Phagocytosis: Complements bind to their receptors on
Phagocytes & facilitate uptake & destruction of
pathogens by Phagocytes.
2. Cell lysis: MAC makes pores on the surface of cells and
lead to cell lysis.
3. Inflammatory response: Complements released during
cascade like C3a, C4a, C5a are anaphylatoxins which
cause Mast cell degranulation which bring about
inflammatory response.
4. Opsonization: C3b & C4b are the major opsonins that
bind to immune complexes & enhance their
phagocytosis.

12. 5. Hypersensitivity reaction: Complements participate in
both type 2 HST (Transfusion reaction) & type 3 HST
reactions (Serum sickness/Arthus reaction).
6. Play role in autoimmune diseases like autoimmune
hemolytic anaemia.
7. Play role in Endotoxin mediated shock: Endotoxin
mediated C3 fixation & Platelet adherence leading to DIC
(Disseminated Intravascular Coagulation).
8. Chemotaxis: Movement of phagocytic cells towards
bacterial cells with the help of C5a.
9. Immune clearnace: C3b bind to immune complexes and
they are then removed from blood in liver/spleen.
10. Neutralization of Viruses: Complements neutralize
viruses by lysis of viruses/opsonization of viruses/blocking
their attachment sites.

13. Evasion of Complement system
Mechanism of Evasion Examples
Lipopolysaccharide side chains
prevent insertion of MAC
E coli
MAC fails to enter bacterial
membrane
Neisseria gonorrhoea
Elastases inactivate C3a & C5a Pseudomonas
Thick cell wall prevent
insertion of MAC
Staphylococcus/ Streptococcus
Bacterial capsule provides
extra physical barrier
Streptococcus pneumoniae
Proeins mimicking
complement regulator proteins
Vaccinia virus, EB virus,
Herpes simplex virus etc

14. Complement deficiencies &
associated syndromes
Deficiency Syndrome
C1 inhibitor Hereditary angioneurotic
edema
C1, C2, C4 SLE & other collagen
vascular diseases
C3 & its regulator proteins Recurrent pyogenic
infections
C5-C9 Disseminated Neisseria
infections

15. Thank you