Acute Inflammation Pathogenesis

Acute Inflammation Pathogenesis

• Learning Objectives: Students will be able to evaluate leukocyte recruitment, understand the role of neutrophils and macrophages in eliminating pathogens, classify acute inflammation types, and correlate inflammation subtypes with clinical conditions.

Leukocyte Recruitment

• Neutrophils and macrophages are recruited to sites of inflammation to recognize pathogens and damaged tissue, eliminating them and facilitating repair.
• The type of leukocyte recruited depends on the initial stimulus and inflammation duration:
  • Bacterial infections primarily recruit neutrophils.
  • Viral infections recruit lymphocytes.
  • Allergic reactions increase eosinophils.
  • Hypersensitivity reactions lead to mixed infiltrates.
  • Necrosis initially induces a neutrophilic response, transitioning to monocytes after 24-48 hours.

Leukocyte Movement

• Leukocytes move from blood vessels to tissue in a multi-step process:
  • Margination, rolling, and adhesion to endothelium.
  • Transmigration across endothelium.
  • Migration towards chemoattractants (chemotaxis).
  • Apoptosis of neutrophils (within 24-48 hours), while monocytes survive longer.

Leukocyte Adhesion

• Leukocyte rolling, adhesion, and transmigration are driven by interactions between complementary adhesion molecules on leukocytes and endothelium.
• Important adhesion molecules include selectins (initiating weak interactions), and integrins (for firm adhesion).
• Cytokines like TNF and IL-1 enhance adhesion molecule expression.

Leukocyte Transmigration

• Leukocytes migrate through the endothelium by squeezing between cells at endothelial junctions.
• They traverse the basement membrane after secretion of collagenases.

Chemotaxis

• Chemotaxis is the directional movement of leukocytes along a chemical gradient guided by chemoattractants (e.g., bacterial products, cytokines).

Phagocytosis

• Phagocytosis is the process of recognizing, attaching, engulfing, and destroying pathogens.
• Phagocytic receptors on leukocytes recognize microbes, and opsonins (like IgG and C3b) enhance recognition.
  • The ingested material is destroyed by reactive oxygen species (ROS), reactive nitrogen species (like NO), and lysosomal enzymes.

Role of Neutrophils and Macrophages

• Neutrophils and macrophages contain granules with enzymes, lysozyme, myeloperoxidase, and anti-microbial proteins; they degrade microbes, dead tissues, and contribute to tissue damage.

ROS and Nitric Oxide Production

• ROS (like hydrogen peroxide, hypochlorite, and hydroxyl radical) are produced within the phagolysosome; they are potent antimicrobial agents.
• NO is produced by inducible nitric oxide synthase (iNOS); it reacts with superoxides to create peroxynitrite, damaging microbial lipids, proteins, and nucleic acids.

Other Leukocyte Functions

• Activated leukocytes, predominantly macrophages, produce cytokines to amplify/limit inflammation, growth factors stimulating tissue repair (e.g., fibroblasts, collagen), and enzymes that remodel connective tissues.

Termination of the Inflammatory Response

• Inflammatory mediators are produced transiently and are eliminated; stop signals (e.g., anti-inflammatory cytokines like TGF-β and IL-10) regulate inflammation.
• Signs of acute inflammation include vascular dilation, leukocyte & fluid accumulation in tissues.

Serous Inflammation

• Exudation of cell-poor fluid into spaces, often from body cavities (e.g., pleura, peritoneum).

• Fluid is not typically infected.

  • Examples include skin blisters resulting from burns or viral infections, or effusions in body cavities.

Fibrinous Inflammation

• Large increase in vascular permeability results in exudation of high-molecular weight proteins (such as fibrinogen).
• Fibrinous exudate forms a meshwork/coagulum.
  • Occurs in lining of body cavities like meninges, pericardium, and pleura.

Purulent (Suppurative) Inflammation

• Characterized by pus production
• Result of pathogenic bacteria, particularly those producing liquefactive tissue necrosis (e.g., staphylococcus).
  • Localized collections of pus (abscesses) are common outcomes.

Ulcers

• Ulcers are tissue defects resulting from sloughed necrotic tissue, often in areas with chronic inflammation (e.g., stomach, duodenum, lower extremities).

Explore the mechanisms of acute inflammation in this quiz. Assess the roles of leukocytes like neutrophils and macrophages in combating pathogens, the types of acute inflammation, and their clinical relevance. Understand how different stimuli influence leukocyte recruitment and movement.