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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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The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Sympathetic Activation01:16

Sympathetic Activation

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The sympathetic division can influence tissues and organs by releasing norepinephrine at peripheral synapses and distributing epinephrine and norepinephrine through the bloodstream. In times of crisis or stress, sympathetic activation occurs, which is regulated by sympathetic centers in the hypothalamus. As a result, sympathetic activation prepares the body for physical exertion, rapid ATP production, and heightened alertness, allowing individuals to respond effectively to challenging or...
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cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

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The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
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Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

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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.
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Complete antigens possess both immunogenicity and...
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Related Experiment Video

Updated: Dec 14, 2025

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

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SARS-CoV2 drives JAK1/2-dependent local and systemic complement hyper-activation.

Bingyu Yan1, Tilo Freiwald2, Daniel Chauss2

  • 1Departments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN, USA.

Research Square
|July 24, 2020
PubMed
Summary
This summary is machine-generated.

The complement system is unexpectedly activated by SARS-CoV-2 infection, impacting disease severity. JAK inhibitors like Ruxolitinib show potential in normalizing these pathways for COVID-19 treatment.

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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
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Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
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Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

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Area of Science:

  • Molecular Biology
  • Immunology
  • Virology

Background:

  • Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, presents severe multi-organ manifestations.
  • The precise intracellular pathways driving COVID-19 pathogenesis remain incompletely understood.
  • Angiotensin-converting enzyme 2 (ACE2) is a key SARS-CoV-2 entry receptor, highly expressed in affected tissues.

Approach:

  • Investigated intracellular pathways induced by SARS-CoV-2 in lung and liver cells.
  • Analyzed complement system activation signatures in patient bronchoalveolar lavage cells.
  • Modeled host gene regulation and identified potential therapeutic targets using computational analysis.

Key Points:

  • The complement system is significantly induced intracellularly by SARS-CoV-2 infection.
  • Complement activation patterns in immune and epithelial cells correlate with COVID-19 disease severity.
  • JAK1/2-STAT1 signaling is implicated in the host response to SARS-CoV-2.

Conclusions:

  • Ruxolitinib, a JAK1/2 inhibitor, normalized key SARS-CoV-2-induced genes, including complement-related genes and IL-6.
  • The JAK1/2-STAT1 pathway, downstream of type I interferon receptors, is a critical target.
  • Combination therapy with JAK inhibitors and NF-kB-targeting agents may offer an effective clinical strategy for COVID-19.