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Related Concept Videos

Complement System01:27

Complement System

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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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Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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The Tumor Microenvironment02:17

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Cytotoxic T Cells-mediated Immune Response01:27

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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Antimicrobial Proteins01:23

Antimicrobial Proteins

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Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
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Antibody Actions01:26

Antibody Actions

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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.
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Related Experiment Video

Updated: Nov 25, 2025

Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
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Complement controls the immune synapse and tumors control complement.

Alan Herbert1

  • 1Discovery, InsideOutBio Inc, Charlestown, Massachusetts, USA alan.herbert@insideoutbio.com.

Journal for Immunotherapy of Cancer
|December 16, 2020
PubMed
Summary
This summary is machine-generated.

The complement system

Keywords:
immune toleranceimmunityimmunotherapyinflammationinnatetumor escape

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Area of Science:

  • Immunology
  • Complement System Biology
  • Molecular Mechanisms of Immune Response

Background:

  • Immune cell responses (IRs) are regulated at synapses, narrow junctions between immune cells and targets.
  • Self-nonself discrimination is crucial for preventing autoimmunity and effectively targeting pathogens or abnormal cells.

Purpose of the Study:

  • To propose a mechanism for immune self-nonself discrimination based on complement protein C3 fragments.
  • To elucidate the role of complement receptor 3 (CR3) in mediating these discrimination processes.

Main Methods:

  • Analysis of complement protein C3 proteolytic fragments (C3d and iC3b) and their interaction with CR3.
  • Investigation of CR3 conformational changes (cis-acting vs. transacting) and their functional consequences.
  • Examination of synapse formation and immune cell activation dynamics.

Main Results:

  • CR3 exhibits distinct conformations to bind C3d (activating) and iC3b (inhibitory).
  • The size of C3d allows it to fit within the synapse, promoting immune cell activation.
  • iC3b binding to CR3 at the synapse edge inhibits immune responses, facilitating self-tolerance.
  • Host cells use regulators of complement activation (RCA) to coat themselves with iC3b, preventing self-attack.
  • Tumors exploit this mechanism by masking neoantigens with iC3b, evading immune surveillance.

Conclusions:

  • A C3 checkpoint mechanism involving CR3 regulates immune cell activation based on the balance of C3d and iC3b.
  • Targeting cancer cells with C3d therapeutics can enhance synapse formation and boost anti-tumor immunity by labeling them as nonself.