Immunology Quiz on Leukocyte Recruitment

Overview of Inflammation: Definitions and General Features

• Inflammation is a vascularized tissue response that delivers leukocytes and host defense molecules to sites of infection or cell damage to eliminate the threat.
• Inflammation is a protective response essential for survival.
• Inflammation involves phagocytic leukocytes, antibodies, and complement proteins.
• Inflammation normally resides in the blood, capable of rapid recruitment to any body site.
• Inflammation includes processes that deliver cells and proteins into tissues, activating recruited cells/proteins to eliminate harmful substances.
• The suffix "-itis" signifies inflammation in a specific organ (e.g., appendicitis, conjunctivitis).
• The inflammatory reaction follows a series of steps.

Historical Highlights

• Clinical observations of inflammation date back to 3000 BCE (Egyptian papyrus).
• Celsus (1st century AD) identified the four cardinal signs of acute inflammation: redness, swelling, heat, and pain.
• John Hunter (1793) recognized inflammation as a body response, not a disease.
• Elie Metchnikoff (1880s) discovered phagocytosis.
• Thomas Lewis emphasized the role of chemical mediators of inflammation.

Causes of Inflammation

• Infections (bacterial, viral, fungal, parasitic) and microbial toxins are the most common causes.
• Tissue necrosis from ischemia, trauma, physical/chemical injury triggers inflammation.
• Foreign bodies/endogenous substances (urate crystals, etc.) can trigger inflammation.
• Immune reactions (hypersensitivity) can cause inflammation and tissue damage.

Recognition of Microbes and Damaged Cells

• Sentinel cells (e.g., macrophages) recognize microbial components and damaged cell products triggering an inflammatory response.
• TLRs and other cellular receptors sense foreign invaders.
• Damage-sensing sensors (e.g., NLRs) recognize molecules from damaged cells initiating inflammasome activation and IL-1 production, resulting in inflammation.

Acute Inflammation

• Characterized by:
  • Dilation of blood vessels increasing blood flow
  • Increased microvasculature permeability allowing plasma proteins and leukocytes to leave the blood
  • Leukocyte emigration, accumulation at the site of injury, and their activation to eliminate the offending agent
• The vascular reactions involve changes in blood flow and permeability maximizing the movement of plasma proteins/leukocytes to the site of injury.
• Exudate (high protein, cellular debris) differs from a transudate (low protein).

Increased Vascular Permeability

• Histamine, bradykinin, leukotrienes constrict endothelial cells creating gaps in venules, allowing fluid and proteins to escape.
• Endothelial injury leads to endothelial cell necrosis and detachment.

Leukocyte Recruitment to Sites of Inflammation

• Margination. Red blood cells move to center of blood vessels causing white blood cells (leukocytes) to move to the outer edges of blood vessel.
• Rolling. Leukocytes loosely attach and roll along endothelial walls via selectin molecules.
• Stable adhesion. Rolling is followed by firm adhesion via integrin molecules.
• Migration through endothelium. Leukocytes migrate through the endothelium via gaps between endothelial cells.

Chemotaxis of Leukocytes

• Chemotaxis is the movement of cells along a chemical gradient.
• Exogenous or endogenous substances act as chemoattractants (microbial products, cytokines).
• Macrophages, neutrophils predominate in the first 6-24 hours, replaced by monocytes later.

Phagocytosis and Clearance of Offending Agents

• Phagocytosis. Recognition and attachment of particle to be ingested leading to engulfment and the formation of a phagocytic vacuole and subsequent killing and degradation.
• Phagocytes. Neutrophils and macrophages.
• Phagocytic receptors (e.g., mannose), receptors for opsonins (IgG antibodies, C3b).
• Intracellular destruction. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed inside phagocytic vacuoles, as well as lysosomal enzymes.

Mediators of Inflammation

• Many substances (vasoactive amines, lipid mediators, cytokines, complement system products) initiate/regulate inflammatory reactions.
• Sources of mediators include macrophages, dendritic cells, mast cells.
• These mediators have overlapping actions.
• Mediators are short-lived, thus regulation mechanisms exist.

Systemic Effects of Inflammation

• Fever.
• Acute-phase proteins.
• Leukocytosis.
• Septic shock (severe infection).

Morphological Patterns of Acute Inflammation

• Serous inflammation. Leaking of cell-poor fluid into spaces caused by injury or body cavities.
• Fibrinous inflammation. Increased vascular leakage causing leakage of larger molecules like fibrinogen leading to fibrinous exudate.
• Purulent (suppurative) inflammation & Abscess. Production of pus (neutrophils, liquefied debris).

Chronic Inflammation

• Prolonged, weeks-months.
• Causes: persistent infection, hypersensitivity, prolonged exposure to toxic agents.
• Characterized by mononuclear cell infiltration, tissue destruction, attempts at healing (angiogenesis, fibrosis).
• Granulomatous inflammation. (Formation of granulomas, e.g., in tuberculosis, Crohn's disease).

Cells and Mediators of Chronic Inflammation

• Macrophages: Dominant cells that secrete cytokines/growth factors.
• Lymphocytes: Amplify inflammatory reactions by activating more macrophages via cytokine signaling.
• Other cells: eosinophils, mast cells.

Tissue Repair

• Regeneration of cells/tissues to normal states.
• Connective tissue deposition (scar formation).
• Steps in scar formation: Inflammation, cell proliferation (angiogenesis, fibroblast proliferation), connective tissue deposition (Collagen).

Healing of Skin Wounds

• Healing by primary intention (clean incision): epithelial regeneration (migration, mitosis), granulation tissue filling.
• Healing by secondary intention (large wound): more inflammation, exudate and debris, more granulation tissue, contraction.

Factors that Influence Tissue Repair

• Infection.
• Diabetes.
• Nutrition.
• Glucocorticoids.
• Poor perfusion.
• Foreign bodies.

Test your knowledge on the processes involved in leukocyte recruitment and the role of cytokines in immune responses. This quiz covers topics such as phagocytosis, receptor recognition, and the early cellular response during inflammation. Perfect for students studying immunology and related fields.