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Complement system


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Complement system

  1. 1. Complement cascadeDEEPA BABIN
  2. 2. The multiple activities of thecomplement system.
  3. 3. The complement cascade
  4. 4. Overview of the complement activationpathways.
  5. 5. The Classical Pathway
  6. 6. The building of a C3 activationcomplex
  7. 7. C3 Activation complex
  8. 8. The function of C3a
  9. 9. Membrane Attack complex
  10. 10. Alternative pathway
  11. 11. Overview
  12. 12. Complement DeficiencyDisease Cl inhibitor Hereditary angioneurotic edema Early components of SLE and other collagen Classical pathway C1, Vascular diseases C2,C4 C3 and its regulatory Severe recurrent pyogenicProtein C3b inactivator infections C5 to C8 Bacteremia, mainly with Gram negative diplococci, toxoplasmosis C9 No particular disease
  13. 13. Pathologic effects of a normalcomplement system - The immune complexes produced in autoimmune diseases may bind to vascular endothelium and kidney glomeruli and activate complement (MAC generation). - It initiates the acute inflammatory responses that destroy the vessel walls or glomeruli and lead to thrombosis, ischemic damage to tissues, and scarring. - Some of the late complement proteins activateprothrombinases in the circulation that initiate thrombosis.
  14. 14. CASE STUDIES-Case A Case A: A 23yr man complains of fever (102oF), headache, neck stiffness and fatigue of 2 days duration. Lumbar puncture shows increased pressure with cloudy cerebrospinal fluid containing large numbers of neutrophils, increased protein, decreased glucose and gram negative diplococci. Laboratory studies show C5 (5th component of complement) levels at 18%and normal levels of C2, C3 and C7. The patient recovers after institution of intravenous antibiotic therapy.
  15. 15. ? Case A: Why would this patient be at increased risk for developing bacterial meningitis? What is the relationship among the three pathways of complement activation and bacterial clearance? Would a defect in C2 alone place a patient at increased risk of developing bacterial meningitis? Explain
  16. 16. Case B Case B: A 14yr girl has a long history of excessive swelling after mild traumatic injury. During the past 2 years she has complained of 7 episodes of intermittent abdominal pain sometimes accompanied with watery diarrhea. Laboratory tests show decreased levels of C4 and normal C3 levels. C1 inhibitor levels are 20% of normal
  17. 17. ? What pathologic changes would explain this patients symptoms? What is the effect of defective C1 esterase levels on complement system regulation? What other inflammatory mediator systems are effected by C1esterase inhibitor? Why are these patients not at significant risk for bacterial infection?