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 Lysis of bacteria (Vibrio Cholerae) Hemolysis Paul Ehrlich
History Jules Bordet1890s 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., Complement Activation IgM, IgG1,2,3 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 Alternative Pathway Factor H, 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 Functions of Complement Complement Receptors Deficiency of Complement System Classical Pathway 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 C1q, C1r, C1s, C4,C2 homozygous deficiencies C1q, C1r, C1s, C4,C2 homozygous deficiencies Factor D & properdin deficiencies
Alternative Pathway Factor D & properdin deficiencies Neisseria Infection Classical & Alternative Pathways
Homozygous deficiencies in components involved in the MAC formation Immune Complex Disease Recurrent Bacterial infections C3 dificiency Congenital Deficiency of Complement Regulatory Proteins
C1 inhibitor deficiency Hereditary angioedema DAF & CD59 deficiency Paroxymal nocturnal hemoglobinuria