oral medicine and periodontology

1. COMPLEMENT SYSTEM
By:
Nadia Hamdy Ibrahim Mohammed Aref
Mansoura University
Oral medicine , periodontology department

2. ‫الرحيم‬‫الرحمن‬ ‫هللا‬ ‫بسم‬

4. The complement system refers to a series of >20 proteins, circulating in the blood
and tissue fluids.
Complement proteins are synthesized mainly in the liver, but tissue macrophages
and fibroblasts can synthesize some complement proteins as well
The complement system was first identified as a heat-sensitive proteins in fresh
serum that 'complemented' the effects of specific antibody in the lysis of bacteria
and red blood cells

5. Although first discovered as an effector arm of the antibody response, complement
can also be activated early in infection in the absence of antibodies. Indeed, it now
seems clear that complement first evolved as part of the innate immune system,
where it still plays an important role.
 Most of the proteins are normally inactive, but in response to the recognition of
molecular components of microorganisms they become sequentially activated in
an enzyme cascade – the activation of one protein enzymatically cleaves and
activates the next protein in the cascade.

6. Effector functions of activated complement
- Cytolysis (MAC)
- Opsonization (C3b)
- Stimulation of inflammation (C5a, C3a, C4a)
- Immune complex clearance (C3b)

9. Immune complex clearance (C3b)

10. Immune complex clearance (C3b)

12. Classical Pathway:
This pathway involves complement components C1, C2 and C4. The pathway is
triggered by antibody-antigen complexes binding to C1, which itself has three
subcomponents C1q, C1r and C1s. The pathway forms a C3 convertase, C4b2a,
which splits C3 into two fragments; the large fragment, C3b, can covalently
attach to the surface of microbial pathogens and opsonise them; the small
fragment, C3a, activates mast cells, causing the release of vasoactive
mediators such as histamine. C5a attract macrophages and neutrophils to site
of infection. Notice that macrophages have receprors for c3b and bind to fc
portion of antibodies which leads to opsonization.

13. Alternative Pathway:
This pathway involves various factors, B, D, H & I, which interact with each other,
and with C3b, to form a C3 convertase, C3bBb, that can activate more C3, hence
the pathway is sometimes called ‘the amplification loop’. Activation of the loop
is promoted in the presence of bacterial and fungal cell walls, but is inhibited by
molecules on the surface of normal mammalian cells.

14. Mannose-binding Lectin
Pathway:
This pathway is activated by the binding of mannose-binding
lectin (MBL) to mannose residues on the pathogen surface. This
in turn activates the MBL-associated serine proteases, MASP-
1 and MASP-2, which activate C4 and C2, to form the C3
convertase, C4b2a.

15. Lytic Pathway (MAC):
This pathway is initiated by the splitting of C5, and attachment of C5b to a
target. C6, C7, C8 and C9 unite with C5b, and this membrane-attack
complex (MAC), when inserted into the outer membrane of some bacteria,
can contribute to their death by lysis. Red cells which have antibody bound
to the cell surface can also activate the classical and lytic pathways, and
become susceptible to lysis.

16. Classical
Lectin
Alternatve
C1, C4, C2
Early steps Late steps
MBL, C4, C2
C3, B, D (P)
C3, C5, C6, C7, C8, C9
C3, C5, C6, C7, C8, C9
C3, C5, C6, C7, C8, C9
Activation
pathway

17. Q: Why does not
complement attack
our cells?

18. • Because it is switched on when it senses pathogans
• And because of regulatory protiens that are found in plasma
and also attached to our cells which able to switch off
complement .
• Many of these regulatory protiens are formed in the liver

20. Q2:What happens when our
regulatory protiens are not
working properly?

21. • Hereditary angioedema:
• (HAE) is a disease caused by deficiency of the CP control protein, C1-
Inh. Symptoms generally begin around puberty but can occur earlier.
These individuals have recurrent swelling in the extremities, face, lips,
larynx or GI tract. The patients describe a sensation of fullness often
experience acute abdominal pain. The latter two presentations are of
the most concern because suffocation can occur if the airways are
obstructed, and the acute swelling of the abdominal region produces
intense pain often resulting in exploratory surgery. The mechanism for
production of the swelling involves not the complement enzymes, but
the kinin-generating pathway. It is the production of Bradykinin through
this pathway that is responsible for the tissue permeability changes that
cause the swelling.

22. Complement attack our cells by alternative pathway causing diseases'
such as :
Membranoproliferative glomerulonephritis
it occur in some diseases as Autoimmune diseases (systemic lupus
erythematosus, Sjögren syndrome, sarcoidosis) also in infectious
diseases as hepatitis c and b

23. Deficiency of complement:

24. • 1-Deficiency of C3 and C5 are
associated with recurrent infection.
But that happens in children and
young age but once they are adult
anti bodies are formed enough to
take the action by its own.

25. 1-Rapid clearance of immune complexes, dying cells and debris from
damaged tissues is a job that is performed efficiently by a normal CP. Primary
deficiency of C1q, C1r, C1s or C4 is closely linked to development of systemic
lupus erythematosus (SLE) or rheumatoid arthritis (RA), thought to be due to
the inability of complement to clear immune complexes and dying cells. Small
complexes are cleared from the circulation when they bind to complement
receptors on macrophages in the spleen and liver.

26. Without complement, the complexes can grow too large to be easily cleared
serve as sources of altered self-antigens with the potential for inducing
autoantibodies.

27. Thank you

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