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Related Experiment Videos

Relative inefficiency of terminal complement activation.

S Bhakdi1, W Fassbender, F Hugo

  • 1Institute of Medical Microbiology, University of Giessen, West Germany.

Journal of Immunology (Baltimore, Md. : 1950)
|November 1, 1988
PubMed
Summary
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The complement system

Area of Science:

  • Immunology
  • Biochemistry
  • Complement System Biology

Background:

  • The complement system is crucial for innate and adaptive immunity.
  • Terminal complement pathway activation generates C5b-9 complexes, essential for pathogen lysis and immune regulation.
  • Understanding the efficiency of complement cascade steps is vital for comprehending immune responses and related diseases.

Purpose of the Study:

  • To investigate the efficiency of terminal complement complex (SC5b-9 and C5b-9(m)) formation relative to C3 and C5 cleavage.
  • To determine how different activation pathways (fluid-phase, particulate, cellular) and surface properties influence complement cascade efficiency.
  • To elucidate the reasons for low levels of SC5b-9 in healthy individuals and in immune complex diseases.

Main Methods:

Related Experiment Videos

  • Induction of fluid-phase complement activation using purified bacterial antigens in human serum.
  • Utilizing Sephadex beads as particulate activators for the alternative pathway.
  • Employing antibody-coated erythrocytes (rabbit, sheep, human) to study membrane C5b-9(m) complex formation.
  • Quantifying molar ratios of C3a:C5a and C5a:SC5b-9 to assess cascade efficiency.

Main Results:

  • Molar ratios of C3a:C5a ranged from 60-200:1 with soluble immune complexes and 70-150:1 with particulate activators/cells.
  • C5 cleavage efficiency relative to C3 cleavage increased with antibody and C3b-binding site density on surfaces.
  • Soluble immune complex activation showed variable SC5b-9 generation (C5a:SC5b-9 ratios from 30:1 to 1:1), while particle/cell activation yielded ratios near 1:1.
  • Overall inefficiency in terminal complement activation stems from C5 convertase formation/cleavage and C5b utilization.

Conclusions:

  • Terminal complement sequence activation is inefficient due to issues in C5 cleavage and C5b utilization, particularly in fluid-phase reactions.
  • Surface-bound activation enhances C5 cleavage efficiency compared to fluid-phase activation.
  • These inefficiencies explain the low levels of SC5b-9 observed in healthy individuals and patients with complement-consuming immune complex diseases.