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The Complement System Dr. M. Izad Oct 2009 Objectives 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 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., C 4b2a Complement Activation C1 Structure Figure 2-53 part 3 of 3 Innocent bystander lysis Figure 2-35 •Bacteria (Salmonella, Listeria, Nisseria) •Fungi (Cryptococcus Neoformans, Candida Albicans •Viruses ( HIV) Figure 2-24 Regulation of the Complement system Classical Pathway C1 inhibitor Classical & Lectin Pathways C4bBp, CR1, MCP CR1, MCP Alternative Pathway Factor H, CR1, MCP CR1,MCP, Classical & Lectin & Alternative Pathways DAF (CD55) C4bBp, CR1, Factor H C3bBb C3b Regulation at assembly of MAC S protein Regulation at assembly of MAC Homologous restriction factor(HFR) or CD59 /CD59 Functions of Complement Complement Receptors Deficiency of Complement System Classical Pathway • C1q, C1r, C4,C2 •C1q, C1r, C1s,C1s, C4,C2 homozygous homozygous deficiencies deficiencies • Immune Complex Disease such as systemic lupus erythematosus, vasculitis, glomerulonephritis • Recurrent infections by pyogenic bacteria such as streptococci & staphylococci Alternative Pathway • Factor D & properdin deficiencies Neisseria Infection Classical & Alternative Pathways C3 dificiency • Homozygous deficiencies in components involved in the MAC formation • Immune Complex Disease • Recurrent Bacterial infections Congenital Deficiency of Complement Regulatory Proteins • C1 inhibitor deficiency Hereditary angioedema • DAF & CD59 deficiency Paroxymal nocturnal hemoglobinuria