The document summarizes the complement system. It is part of the immune system and consists of proteins that interact in a regulated cascade to eliminate pathogens and damaged cells. There are over 20 complement proteins that are activated via the classical, alternative, or lectin pathways and work in both innate and adaptive immunity. The complement system opsonizes pathogens, causes cell lysis, promotes inflammation, and clearance of immune complexes. Deficiencies or dysregulation of complements can cause diseases.

1. DAVANGERE UNIVERSITY
SEMINAR ON THE TOPIC:
COMPLEMENT PATHWAYS
SUBMITTED BY :
Ponnanna. M.B
M.Sc. Microbiology.

2. CONTENTS
1. Introduction
2. History
3. Components of complement
4. Complement activation
5. Functions of complements
6. Complement regulation
7. Complement related diseases
8. Summary
9. Conclusion
10. References

3. INTRODUCTION
The complement system is a part of the immune system,
consists of a series of proteins that interact with one another
in a highly regulated manner in order to eliminate pathogens
and fight infections. It helps antibodies and phagocytic cells
to clear pathogens and damaged cells, promote inflammation
and attack pathogen’s plasma membrane.
Proteins that take part in the complement system are called
complements. They collectively work as a biological cascade
and sequence of reactions, each being the catalyst for the
next. Complement activation is triggered by an antibody
when it is bound to the antigen. It can also be triggered by
some components of innate immunity. Thus the complement
system works in both innate and adaptive immunity.

4. HISTORY
• Research on complement began in the 1890s , when Jules
Bordet showed that ,sheep antiserum to the bacterium
Vibrio cholerae caused lysis of the bacteria. And on
heating the antiserum, it destroyed its bacteriolytic
activity. But the ability to lyse the bacteria was restored to
the heated serum by adding fresh serum that contained no
antibodies.
• Paul Ehrlich in Berlin independently carried out similar
experiments and coined the term complement, defining it
as “the activity of blood serum that completes the action
of antibody”. In further years, researchers discovered that
action of complement was the result of interactions of a
large and complex group of proteins.

5. Components of Complement
The soluble proteins and glycoproteins that constitute complement
system are synthesized mainly by liver hepatocytes ,however
significant amount are produced by blood monocytes ,tissue
macrophages and epithelial cells of GI tract.
More than 20 types of complements are present in serum, found
circulating normally in human body in inactive forms (called as
zymogens or proenzymes).
Complements are mainly denoted by the capital letter C with numbers
like: C1,C2,C3 and so on. Some have only alphabets like B, D. Some
are simply represented by names like homologous restriction factor.
C1 has three sub-units C1q, C1r ,C1s and C2,C3,C4,C5 have two
components a and b. Larger subunits are denoted by ‘b’ which binds to
target near site of activation. Whereas the smaller subunits are denoted
by ‘a’ (except C2a which is larger than C2b) which initiate localized
inflammatory response by binding to specific receptors.

6. Complement Activation
The complement activation occurs via three pathways:
1.Classical pathway
2.Alternative pathway
3.Lectin pathway (or mannose binding lectin pathway)

7. 1. Classical Pathway

8. 2. Alternative Pathway

9. 3.Lectin Pathway

11. Functions of Complements
1.Opsonization and phagocytosis
C3b, bound to immune complex or coated on the surface of pathogen,
activate phagocytic cells. These proteins bind to specific receptors on the
phagocytic cells to get engulfed.
2.Cell lysis
Membrane attack complex formed by C5b6789 components ruptures the
microbial cell surface which kills the cell.
3.Chemotaxis
Complement fragments attract neutrophils and macrophages to the area
where the antigen is present. These cell surfaces have receptors for
complements like C5a, C3a .Thus, run towards the site of inflammation,
i.e. chemotaxis.
4.Production of antibodies
B cells have receptor for C3b. When C3b binds to B-cell, it secretes more
antibodies. Thus C3b is also an antibody producing amplifiers which
converts it into an effective defense mechanism to destroy invading
microorganism.

12. 5.Immune clearance
The complement system removes immune complexes from circulating and
deposits them in the spleen and liver. Thus it acts as anti-inflammatory
function. Complement proteins promote the solubilization of these
complexes and their clearance by phagocytes.
6.Activation of mast cells and basophils and enhancement
of inflammation
The proteolytic complement fragments C5a, C4a, and C3a induce acute
inflammation by activating mast cells and neutrophils. All three peptides
bind to mast cells and induce degranulation, with the release of vasoactive
mediators such as histamine. These peptides are also called anaphylatoxins
because the mast cell reactions they trigger are characteristic of anaphylaxis.
Binding to specific complement receptors on cells of the immune system,
they trigger specific cell functions, inflammation, and secretion of
immunoregulatory molecules.

14. Complement regulation
The complement system has the potential to be extremely
damaging to host tissues, hence regulatory mechanisms
are required to restrict the complement pathway. Various
plasma and cell membrane proteins regulate complement
activation by inhibiting different steps in the cascade.
Several mechanisms exist to prevent uncontrolled
activation of complement system.
1. Passive mechanism of regulation
2. Active mechanism of regulation.

15. Complement related Diseases
Diseases associated with complements can be due to the deficiencies
in any of the protein components or in regulatory components.
Some examples of complement protein deficiencies are:
• Deficiency of C2 and C4 can cause systemic lupus erythematosus;
deficiency of C3 and factor D can cause pyogenic bacterial
infection; and deficiency of C5-C9 (or MAC deficiency) may lead
to the Neisserial infections like, gonorrhea and meningitis.
• Deficiencies of regulatory proteins lead to too much activation of
complements in wrong time and place which leads to unwanted
inflammation and cell lysis. Pyogenic bacterial infection and
glomerulonephritis are the results of such deficiencies.
• Mutations in the complement regulators factors may lead to
atypical hemolytic uremic syndrome, age-related macular
degeneration, hereditary angioedema etc.
• Complement system can also be stimulated by abnormal stimuli
like persistent microbes, antibody against self antigens or immune
complexes deposited in tissues. Even when the system is properly
regulated and activated, it can cause significant tissue damage.

16. SUMMARY
Complement system comprises of group of serum
proteins that complement the action of antibody leading
to a cascade of reactions that occurs on the surface of
pathogen and generate active components with various
effector functions.
Complement system is activated by three pathways
namely classical , alternative and lectin pathway.
Complement system participate in both innate and
adaptive immunity.

17. CONCLUSION
The complement system plays a vital role in enhancing
the ability of antibodies and phagocytic cells to clear
pathogens and damaged cells from the host body.
Deficiency of complement factors may lead to
complement associated diseases, on the contrary
regulation of complement activation is also necessary to
avoid damage to host tissues and normal functioning of
the immune system.

18. REFERENCES
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