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