Inflammation and Leukocyte Functions Quiz

Inflammation

• Inflammation is a complex host response to eliminate foreign invaders
• It's a protective response involving host cells, blood vessels, and proteins
• The goal is to eliminate the cause of injury, necrotic cells, and tissues, initiating repair
• Inflammation accomplishes this by diluting, destroying, or neutralizing harmful agents (e.g., microbes, toxins)

Classification of Inflammation

• Acute inflammation: rapid onset, short duration (minutes to days)
  • Characterized by fluid and protein exudation and neutrophilic leukocyte accumulation
• Chronic inflammation: insidious, longer duration (days to years)
  • Characterized by influx of lymphocytes and macrophages, vascular proliferation, and fibrosis (scarring)

Stimuli for Acute Inflammation

• Infections (bacterial, viral, fungal, parasitic)
• Trauma (blunt and penetrating)
• Tissue necrosis (from any cause, including ischemia)
• Foreign bodies (splinters, dirt, sutures)
• Immune reactions (hypersensitivity)

Recognition of Microbes, Necrotic Cells and Foreign Substances

• Phagocytes, dendritic cells, and epithelial cells recognize infectious pathogens and substances from dead cells
• Pattern recognition receptors identify common structures on microbes and dead cells
• Examples include Toll-like receptors and the inflammasome

Vascular Changes

• Increased blood flow (vasodilation) and vascular permeability
  • Bringing blood cells and proteins to sites of injury or infection
• First, brief vasoconstriction, then vasodilation
  • Local increase in blood flow, engorgement of capillaries
    • Redness (erythema) and warmth result from this expansion
• Increased vascular permeability leads to protein rich fluid escaping into extravascular tissue
  • Exudate (high protein content, white and red blood cells) vs transudate (low protein content, few cells)
  • Fluid accumulation in tissues, causing edema

Cellular Events: Leukocyte Recruitment and Activation

• Leukocytes are delivered to sites of injury or activation
• Ingest offending agents, kill microbes, and eliminate necrotic tissue
• Can induce tissue damage and prolong inflammation
  • Host defense mechanisms have regulatory checks and balances

Leukocyte Recruitment

• Leukocytes move from the blood stream to the site of injury (extravascular space)
• Sequence includes:
  • Margination and rolling along vessel walls
  • Firm adhesion to endothelium
  • Transmigration between endothelial cells
  • Migration into interstitial tissues following a chemotactic stimulus
• Chemical mediators (chemoattractants and cytokines) influence adhesion molecules, binding affinity of leukocytes, and directional movement

Leukocyte Activation

• Recruitment to sites of infection or tissue necrosis
• Activation necessary for their functions
• Stimuli include microbes, products of necrotic cells, and mediators
• Various receptors on leukocytes detect microbes, dead cells, and foreign substances
• Inducing responses part of normal defensive functions, grouped under 'activation'

Phagocytosis

• Three steps in phagocytosis:
  • Recognition and attachment of the particle (microbes, dead cells) to the leukocyte via opsonins.
  • Engulfment, forming a phagocytic vacuole
  • Killing and degradation of the ingested material within lysosomes.

Outcomes of Acute Inflammation

• Resolution: Regeneration and repair if injury limited
• Chronic inflammation: if the offending agent is not removed; repair or scarring may result
• Scarring: Tissue destruction leads to connective tissue filling (fibrosis)

Morphologic Patterns of Acute Inflammation

• Serous inflammation: Watery, protein-poor fluid (e.g., blisters)
• Fibrinous inflammation: Large amounts of fibrinogen allowing leakage (severe injury)
• Suppurative (purulent) inflammation: Pus formation (e.g., abscesses); neutrophils, necrotic cells, edema fluid
  • Focal collections of pus caused by pyogenic organisms, or as secondary infections of necrotic tissue
• Ulcers: Local defects in tissue surfaces due to cell necrosis and shedding