Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Hypersensitivity Reactions: Immune-Complex Reactions01:19

Hypersensitivity Reactions: Immune-Complex Reactions

Type III hypersensitivity reactions occur when antigen–antibody complexes form and activate the complement system. Normally, these complexes help the clearance of antigens by phagocytes and red blood cells. However, when large numbers of immune complexes are present, they can deposit in tissues—particularly in the walls of blood vessels—leading to inflammation and tissue injury. These deposits trigger complement activation and neutrophil recruitment, resulting in serum sickness, a systemic...
Antibody Actions01:26

Antibody Actions

Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Complement System01:27

Complement System

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 membrane...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Allergic Drug Reactions01:27

Allergic Drug Reactions

Allergic reactions related to drugs are hypersensitivity responses driven by the immune system and bear no connection to the drug's therapeutic action. While drugs in isolation do not trigger an immune response, they can interact with endogenous proteins to form antigens. These antigens stimulate lymphocytes to produce antibodies. IgE-type antibodies attach themselves to mast cells. Upon subsequent exposure to the same stimulus, the antigen-antibody interaction is initiated, unleashing numerous...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mechanisms tagging senescent red blood cells for clearance in healthy humans.

Frontiers in physiology·2014
Same author

Naturally occurring anti-band 3 antibodies in clearance of senescent and oxidatively stressed human red blood cells.

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie·2013
Same author

Comment Concerning the Role of CD47 and Signal Regulatory Protein Alpha in Regulating the Clearance of Aged Red Blood Cells.

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie·2013
Same author

Naturally occurring antibodies.

Advances in experimental medicine and biology·2012
Same author

Naturally occurring autoantibodies in mediating clearance of senescent red blood cells.

Advances in experimental medicine and biology·2012
Same author

Naturally occurring antibodies/autoantibodies in polyclonal immunoglobulin concentrates.

Advances in experimental medicine and biology·2012

Related Experiment Video

Updated: May 19, 2026

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
06:29

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells

Published on: January 29, 2014

How immune complexes from certain IgG NAbs and any F(ab')₂ can mediate excessive complement activation.

Hans U Lutz1

  • 1Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Hönggerberg, Zurich, Switzerland. hans.lutz@bc.biol.ethz.ch

Advances in Experimental Medicine and Biology
|August 21, 2012
PubMed
Summary

Excessive immune complexes (IC) involving IgG or F(ab')₂ fragments drive sepsis mortality by amplifying complement activation. These ICs, particularly F(ab')₂-IC with anti-hinge antibodies, potently stimulate the complement cascade, leading to severe inflammation.

More Related Videos

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
07:25

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis

Published on: May 4, 2017

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
04:47

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies

Published on: February 23, 2018

Related Experiment Videos

Last Updated: May 19, 2026

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
06:29

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells

Published on: January 29, 2014

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
07:25

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis

Published on: May 4, 2017

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
04:47

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies

Published on: February 23, 2018

Area of Science:

  • Immunology
  • Complement System Biology
  • Sepsis Pathophysiology

Background:

  • Sepsis mortality is linked to excessive inflammation driven by the complement system, primarily through C3/C5 convertase activation.
  • Immune complexes (IC), especially those containing IgG or F(ab andomIndex)₂ fragments, are key activators of complement amplification.
  • The alternative pathway of complement is amplified by properdin, with C3b acting as a crucial component.

Purpose of the Study:

  • To elucidate the mechanisms by which IgG-IC and F(ab andomIndex)₂-IC stimulate complement amplification in sepsis.
  • To investigate the role of Fab affinity for C3 and the formation of secondary ICs in complement activation.
  • To compare the potency of C3b₂-IgG-IC and C3b₂-F(ab andomIndex)₂-IC/anti-hinge NAbs in stimulating complement amplification.

Main Methods:

  • Analysis of IgG-containing and F(ab andomIndex)₂-containing immune complexes (IC) in the context of complement activation.
  • Investigation of the interaction between C3b and the Fab regions of IgG and F(ab andomIndex)₂ fragments.
  • Characterization of secondary IC formation involving anti-hinge NAbs and F(ab andomIndex)₂-IC.
  • Quantification of complement amplification stimulated by different IC types in conjunction with properdin.

Main Results:

  • Both IgG-IC and F(ab andomIndex)₂-IC can capture dimeric C3b, acting as precursors for alternative C3 convertases.
  • IgG-IC capture dimeric C3b via Fab affinity for C3, a property rare in natural antibodies (NAbs).
  • F(ab andomIndex)₂-IC capture dimeric C3b when forming secondary ICs with anti-hinge NAbs, which rigidify the complex.
  • C3b₂-IgG-IC and C3b₂-F(ab andomIndex)₂-IC/anti-hinge NAbs stimulate complement amplification up to 750 times more effectively than C3b and properdin alone.
  • F(ab andomIndex)₂ fragments, generated during sepsis, evade Fc-receptor clearance, prolonging circulation and enhancing secondary IC formation.

Conclusions:

  • Excessive complement amplification by specific immune complexes significantly contributes to sepsis-induced inflammation and mortality.
  • F(ab andomIndex)₂-IC, particularly when forming secondary complexes, represent a potent pathway for complement overactivation in sepsis.
  • Understanding these IC-mediated complement pathways offers potential therapeutic targets for managing sepsis.