Updated: 1/4/2021

Complement

0%
Topic
Review Topic
0
0
N/A
N/A
Questions
0 4
0
0
100%
0%
Videos
0 1
Overview

Introduction
  • The complement system is a group of circulating proteins that
    • are synthesized by the liver
    • participate in humoral immunity
    • act as proteases and cleave one another in cascade
    • bind to pathogens as well as immune complexes
    • alert phagocytes of the innate immune system
  • The system can be activated in one of three ways including
    • the classical pathway
      • when activated by antibodies
    • the alternative pathway
      • when activated spontaneously
    • the lectin pathway when
      • activated by mannose residues on pathogens
  • Activation of the complement pathway leads to
    • a cascading cleavage of downstream proteins
    • seperation of protein fragments after cleavage where
      • a is the smaller component that is carried by the bloodstream
      • b is the larger component that stays on the pathogen
  • Complement must be closely controlled by inhibitors such as
    • C1 esterase inhibitor
    • CD55 (decay accerating factor)
Activation of Complement
Complement Activation Pathways
Feature Classical  Alternative Lectin
Detects • Surfaces with bound antibodies (IgG and IgM)
• Surfaces not protected by complement inhibitors 
• Surfaces with mannose
Specificity • Conferred by the specific binding of antibodies
• Conferred by inactivation of complement by host inhibitors
• Conferred by lack of mannose on host membranes
Initiating factor • C1q
• C1r
• C1s
• C3 factor turnover
• Factor D
• Mannose binding lectin and associated proteases
C3 convertase • C4b
• C2b
• C3b
• Factor Bb
• C4b
• C2b
 
Functions
  • The complement cascade has many functions including
    • opsonization of invading pathogens mediated by
      • coating of pathogens by C3b and IgG
      • activation of phagocytosis by these fragments
    • clearance of immune complexes and cellular debris
    • chemotaxis of neutrophils mediated by
      • release of C5a into bloodstream after cleavage
      • detection of C5a by innate immune cells
    • direct cytolysis of pathogens through
      • formation of the membrane attack complex (MAC)
      • insertion of the MAC into bacterial membranes
      • rupture of the cell with release of internal contents
    • vascular changes such as dilation that 
      • are caused by immune reaction to C3a, C4a, and C5a
      • can lead to anaphylaxis if released systemically
  • Together these effects of the complement cascade are important in
    • initial activation of the innate immune system
    • clearance of debris such as immune complexes
    • assistance with humoral immunity
Complement Component Deficiencies
 
Complement Component Deficiencies
Missing Factor Presentation
Pathology
Circulating C3
  • Recurrent infection by pyogenic bacteria
  • Increased susceptibility to type III hypersensitivity reactions
  • Failure of C3 convertase formation
  • Lack of immune complex and pathogenic bacterial clearance
C5, C6, C7, C8, or C9
  • Increased susceptibility to recurrent Neisseria infections  
  • Failure of membrane attack complex formation
C1 esterase inhibitor
  • Hereditary angioedema 
  • ACE inhibitors are contraindicated
  • Unregulated activation of kallikrein by complement system leading to increased bradykinin activity

Decay accelerating factor (CD55)

  • Paroxysmal nocturnal hemoglobinuria
  • Unregulated activation of complement leads to lysis of red blood cells
 

Please rate topic.

Average 4.8 of 8 Ratings

Questions (4)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
VIDEOS (1)
Topic COMMENTS (23)
Private Note