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The Complement System. Dr. M. Izad Oct 2009. To understand how the complement system works To determine the Role of Complement in the Innate & Acquired Immunity Regulation of complement system To understand the consequences of Deficiency of Complement. Objectives. History.
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The Complement System Dr. M. Izad Oct 2009
To understand how the complement system works To determine the Role of Complement in the Innate & Acquired Immunity Regulation of complement system To understand the consequences of Deficiency of Complement Objectives
History • Jules Bordet 1890s • Lysis of bacteria (Vibrio Cholerae) • Hemolysis • Paul Ehrlich Complement “The activity of blood serum that completes the action of antibody”
Complement ( C ) • Complement consists of a complex series of over 30 soluble & cell-bound Proteins. Many of which are enzymes (proenzyme/zymogen-proteinases). • The biological activities of this system affect both innate & acquired immunity. • They can bind to an antibody molecule or can act independently, to affect various aspects of the immune system.
Complement Components are produced by: • Liver hepatocytes • Macrophages • Blood monocytes • Epitelial cells of gastrointestinal & genitourinary tracts
Complement components are designated by: Neumerals (C1-C9) Letter symbols (e.g., factor D) Trivial names (e.g., homologus restriction factor) The smaller fragment resulting fromcleavage of a component is designated “a” & the larger fragment designated “b” Those complexes that have enzymatic activation are designated by a bar over the number or symbol (e.g.,
Bacteria (Salmonella, Listeria, Nisseria) • Fungi (Cryptococcus Neoformans, Candida Albicans • Viruses ( HIV)
Classical & Lectin & Alternative PathwaysDAF (CD55) C4bBp, CR1, Factor H C3bBb C3b
Regulation at assembly of MACHomologous restriction factor(HFR) or CD59 /CD59
C1q, C1r, C1s, C4,C2 homozygous deficiencies Immune Complex Disease such as systemic lupus erythematosus, vasculitis, glomerulonephritis Recurrent infections by pyogenic bacteria such as streptococci & staphylococci Classical Pathway • C1q, C1r, C1s, C4,C2 homozygous deficiencies
Alternative Pathway • Factor D & properdin deficiencies Neisseria Infection
Homozygous deficiencies in components involved in the MAC formation Immune Complex Disease Recurrent Bacterial infections Classical & Alternative Pathways C3 dificiency
Congenital Deficiency of Complement Regulatory Proteins • C1 inhibitor deficiency Hereditary angioedema • DAF & CD59 deficiency Paroxymal nocturnal hemoglobinuria