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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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Depletion of Specific Cell Populations by Complement Depletion
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Complement in disease: a defence system turning offensive.

Daniel Ricklin1, Edimara S Reis1, John D Lambris1

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania, 401 Stellar Chance, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.

Nature Reviews. Nephrology
|May 24, 2016
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Summary
This summary is machine-generated.

The complement system, vital for defense, can paradoxically drive inflammation and disease, especially with age or in autoimmune conditions. Understanding its dual role offers new therapeutic targets for inflammatory and kidney diseases.

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Area of Science:

  • Immunology
  • Innate Immunity
  • Inflammation Biology

Background:

  • The complement system is a crucial part of innate immunity, traditionally viewed as a host defense mechanism.
  • However, its functions in microbial threat control and debris clearance can promote inflammation and drive immune-mediated diseases.
  • Age, genetic factors, and autoimmune responses can exacerbate these pathological roles.

Purpose of the Study:

  • To review the dual role of the complement system as both a defense mechanism and a driver of inflammation.
  • To summarize key activating, regulatory, and effector mechanisms of complement.
  • To highlight complement's involvement in kidney disease and transplantation, and discuss therapeutic strategies.

Main Methods:

  • Review of recent research on complement activation pathways.
  • Analysis of tipping points between physiological and pathological complement activity.
  • Examination of complement's role in specific clinical contexts like kidney disease and transplantation.

Main Results:

  • The complement system's effector functions can transition from protective to pathogenic.
  • Age and autoimmune conditions significantly influence complement's pro-inflammatory actions.
  • Inappropriate complement activation occurs in response to foreign materials like biomaterials and transplants.

Conclusions:

  • A deeper understanding of complement mechanisms has revealed therapeutic intervention points.
  • Targeting complement activation pathways offers promise for treating inflammatory diseases, particularly in kidney disease and transplantation.
  • Further research is needed to fully harness complement modulation for clinical benefit.