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Inflammatory Response I: Vascular and Cellular01:30

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The inflammatory response is the body's defense against infection, injury, or irritation from bacteria, trauma, toxins, or heat. Inflammation helps locate and destroy pathogens and remove damaged tissue elements to heal the body. During this initial phase, fluid, blood products, and nutrients migrate to the injured area, resulting in redness, heat, swelling, ache, and loss of function. Moreover, signs of systemic inflammation include fever, increased WBC count, malaise, anorexia, nausea,...
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An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
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The immune system's inflammatory response destroys the invading pathogen, permitting the tissue to heal. The changes during the cellular and vascular stages allow exudate formation at the site of inflammation. The inflammatory exudate released from the wound has high protein content and a specific gravity above 1.020.
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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Regulatory/inflammatory cellular response discrimination in operational tolerance.

Priscila Carmona1,2, Yordanka Medina-Armenteros1,2, Amanda Cabral1,2

  • 1Laboratório de Imunologia, Instituto do Coração (InCor), Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brazil.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|July 8, 2019
PubMed
Summary

Operational tolerance (OT) in kidney transplants shows a regulatory immune response to donor antigens and self-antigens, unlike chronic rejection. This selective immune modulation is key to successful transplantation tolerance.

Keywords:
HLA-DR peptideantigen-specific cellular responseimmunoregulationoperational tolerancerenal transplantation

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Area of Science:

  • Immunology
  • Transplantation Science
  • Cellular Biology

Background:

  • Antigen-specific cellular responses are crucial for establishing immune tolerance.
  • Investigating differential modulation of these responses in operational tolerance (OT) after kidney transplantation is essential.
  • Focus on responses to donor antigens, pathogenic antigens, and self-antigens.

Purpose of the Study:

  • To determine if antigen-specific cellular responses are differentially regulated in operational tolerance (OT).
  • To analyze the profiles of immunoregulatory (REG) and pro-inflammatory (INFLAMMA) cytokines in response to specific antigen groups.
  • To elucidate mechanisms underlying successful transplantation tolerance.

Main Methods:

  • Analysis of immunoregulatory (REG) and pro-inflammatory (INFLAMMA) cytokine profiles.
  • Utilized Luminex technology for antigen-specific cellular response analysis.
  • Examined responses to donor human leucocyte antigen (HLA) DR isotype peptides, pathogenic peptides, and self-antigens (Hsp60 peptide).

Main Results:

  • Operational tolerance (OT) exhibits an immunoregulatory cellular response to donor HLA DR isotype peptides, distinct from chronic rejection and healthy individuals.
  • Pro-inflammatory responses to pathogenic peptides are preserved in OT.
  • Cellular autoreactivity to the N6 heat shock protein 60 (Hsp60) peptide shows an immunoregulatory profile in OT, with increased IL4, IL-5, IL-10, and IL-13.

Conclusions:

  • The shift towards an immunoregulatory response in donor indirect alloreactivity is a key mechanism in OT, involving inhibition of several pro-inflammatory cytokines.
  • Differential immunoregulatory response to the Hsp60 peptide suggests a role for regulatory autoimmunity in human transplantation tolerance.
  • Despite potential antigen cross-reactivity, OT demonstrates functional, systemic antigen-specific discrimination.