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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.
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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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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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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Combinatorial cytokine code generates anti-viral state in dendritic cells.

Boris M Hartmann1, Nada Marjanovic1, German Nudelman1

  • 1Department of Neurology, Mount Sinai School of Medicine, Center for Translational Systems Biology , New York, NY , USA.

Frontiers in Immunology
|March 12, 2014
PubMed
Summary

Cytokine combinations from virus-infected cells create unique immune responses. Interferon-beta (IFNβ), tumor necrosis factor-alpha (TNFα), and interleukin-1 beta (IL-1β) are key in generating anti-viral states in dendritic cells (DCs).

Keywords:
DC maturationIFNbIL1bTNFaanti-viral signalingcombinatorial effect

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Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Immune cell responses are influenced by cytokine microenvironments.
  • Paracrine cytokines from virus-infected dendritic cells (DCs) affect naïve DC maturation.

Purpose of the Study:

  • To investigate the combinatorial effects of cytokines in generating an anti-viral state.
  • To identify specific cytokines mediating the anti-viral response induced by virus-infected DCs.

Main Methods:

  • Microarray analysis of gene expression in DCs exposed to IFNβ or virus-infected DC paracrine signaling.
  • Systematic study of cytokine combinations (leave-one-out) secreted by Newcastle disease virus (NDV)-infected DCs.
  • In vitro and in vivo infection studies, and T-cell activation assays.

Main Results:

  • Paracrine signaling from NDV-infected DCs significantly altered gene expression in naïve DCs.
  • Five candidate cytokines (IFNβ, TNFα, IL-1β, TNFSF15, IL28) were identified as regulators of DC maturation markers.
  • IFNβ, TNFα, and IL-1β were confirmed as major contributors to the anti-viral state, validated through various experimental models.

Conclusions:

  • Combinatorial cytokine microenvironments induce distinct DC responses compared to individual cytokines.
  • A cytokine 'code' may direct immune cell responses, offering insights into infection, neoplasia, and autoimmune diseases.
  • Understanding this code can guide the development of novel combinatorial cytokine immunotherapies.