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Related Concept Videos

Inflammatory Response I: Vascular and Cellular01:30

Inflammatory Response I: Vascular and Cellular

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,...
Inflammatory Response II: Inflammatory Exudate and Tissue Repair01:24

Inflammatory Response II: Inflammatory Exudate and Tissue Repair

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.
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the exudate's...
Inflammatory Response01:28

Inflammatory Response

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.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Acute Inflammation I: Inflammatory Response01:26

Acute Inflammation I: Inflammatory Response

Acute inflammation is a rapid, short-lived physiological response to tissue injury or infection, designed to eliminate harmful agents and initiate repair. This tightly regulated process typically lasts from minutes to several days and is triggered by factors such as microbial invasion, physical trauma, or chemical injury.Recognition and Mediator ReleaseThe inflammatory response begins when resident immune cells—such as mast cells, macrophages, and dendritic cells—detect damage-associated...
Acute Inflammation III: Local and Systemic Effects01:25

Acute Inflammation III: Local and Systemic Effects

Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
Chronic Inflammation: Introduction01:12

Chronic Inflammation: Introduction

Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...

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In vivo Imaging Method to Distinguish Acute and Chronic Inflammation
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Distinct Inflammatory Programs Underlie the Intramuscular Lipid Nanoparticle Response.

William Dowell1,2, Jacob Dearborn1,2, Sylvester Languon1,2

  • 1Department of Surgery; Larner College of Medicine, University of Vermont, Burlington, Vermont 05405, United States.

ACS Nano
|November 20, 2024
PubMed
Summary
This summary is machine-generated.

Lipid nanoparticle (LNP) formulations influence immune responses. Certain LNPs trigger inflammation and immune cell activation, crucial for effective vaccines and therapies.

Keywords:
cancer vaccinegene therapyinnate immunityionizable lipidslipid nanoparticlesmRNA therapeuticsmRNA vaccines

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Area of Science:

  • Biotechnology
  • Immunology
  • Molecular Biology

Background:

  • Messenger RNA (mRNA) and lipid nanoparticle (LNP) technologies are pivotal in vaccinology and gene therapy.
  • Understanding the immunogenicity of mRNA/LNPs is crucial for optimizing therapeutic delivery and vaccine design.
  • Some mRNA/LNPs can create an adjuvant-like environment, enhancing immune responses.

Purpose of the Study:

  • To evaluate the adjuvancy of mRNA/LNP components.
  • To investigate the inflammatory and immune cell responses to different LNP formulations.
  • To establish a design framework for mRNA/LNP-based vaccines and therapeutics.

Main Methods:

  • Phenotyping cellular infiltrates at injection sites.
  • Tracking immune cell uptake of mRNA/LNPs.
  • Assessing the inflammatory state using gene expression and single-cell RNA sequencing.
  • Administering various chemically distinct empty LNPs (eLNPs) to muscle tissue.

Main Results:

  • Two classes of inflammatory gene expression programs (Class A and Class B) were identified in response to different LNPs.
  • Class A eLNPs induced significant neutrophil infiltration and myeloid cell accumulation within 24 hours.
  • SM-102-containing LNPs promoted inflammatory chemokine expression in myeloid cells.
  • Direct transfection and activation of myeloid cells, splenocytes, and dendritic cells (including cDC2s) were observed.
  • mRNA and LNPs synergistically provide innate immune stimulation.

Conclusions:

  • mRNA/LNPs can directly activate immune cells, contributing to vaccine efficacy.
  • LNP chemical composition dictates the inflammatory profile and immune cell engagement.
  • This study provides insights into designing effective mRNA/LNP vaccines and therapeutics by controlling immunogenicity.