23. Inflammation - definition, etiology, classification, cellular and biochemical components, adhesion molecules, mediators and inhibitors, receptors, signaling pathways.

Inflammation - definition, etiology, classification, cellular and biochemical components of inflammation, cell adhesion molecules, mediators and inhibitors of inflammation, receptors, and signal-transmitting pathways).

Inflammation is a protective, vascularized tissue response to harmful stimuli (infections, trauma, toxins), aiming to eliminate the cause of injury and initiate tissue repair.

Etiology (Causes)

1. 1 Infections

• Bacterial (e.g., abscess by Staphylococcus aureus ).
• Viral (e.g., hepatitis).
• Fungal and parasitic.

1. 2 Physical and chemical agents

• Trauma (e.g., fractures).
• Burns (thermal or chemical).
• Irradiation.

1. 3 Foreign bodies

• Splinters, sutures, urate crystals (gout)

1. 4 Immune reactions (hypersensitivity)

• Autoimmune diseases (e.g., rheumatoid arthritis).
• Allergies.

Classification

1. 1 Based on duration

• Acute inflammation
• Rapid onset (minutes to hours).
• Predominantly neutrophils.
• Exudation of plasma proteins.
• Chronic inflammation
• Prolonged (weeks to years).
• Lymphocytes, plasma cells, macrophages.
• Tissue destruction and fibrosis.

1. 2 Based on nature of exudate (acute)

Cellular and Biochemical Components

Cellular components

• Neutrophils: First responders in acute inflammation.
• Macrophages: Main cells in chronic inflammation, phagocytosis, cytokine production.
• Lymphocytes: Adaptive immune response, chronic inflammation.
• Mast cells, basophils, eosinophils: Allergic responses and parasitic infections.
• Platelets: Contribute to vascular changes and healing.

Biochemical components

• Plasma proteins: Complement system, coagulation factors, kinin system.
• Acute-phase proteins: CRP, fibrinogen.

Cell Adhesion Molecules (CAMs)

Types

• Selectins (E- selectin, P- selectin, L- selectin)
• Mediate rolling of leukocytes on endothelium.
• Integrins (e.g., LFA- 1, Mac- 1)
• Firm adhesion of leukocytes to endothelium.
• Immunoglobulin superfamily molecules (ICAM- 1, VCAM- 1)
• Bind integrins on leukocytes.

Mediators of Inflammation

1. 1 Cell- derived

Preformed mediators

• Histamine (mast cells, basophils): vasodilation, increased permeability.
• Serotonin (platelets): similar effects.

Newly synthesized

• Prostaglandins (vasodilation, pain).
• Leukotrienes (increased permeability, chemotaxis).
• Cytokines (TNF-α, IL-1): activate endothelium, recruit leukocytes, systemic effects.

1. 2 Plasma- derived

• Complement components (C3a, C5a): anaphylatoxins, chemotaxis.
• Kinin system (bradykinin): vasodilation, pain.
• Coagulation and fibrinolytic systems.

Inhibitors of Inflammation

• Lipoxins (anti- inflammatory lipid mediators).
• IL- 10, TGF- β (suppress cytokine production).
• Corticosteroids (inhibit phospholipase A2, cytokine expression).

Receptors

• Toll-like receptors (TLRs): Recognize microbial products (e.g., LPS, flagellin), activate innate immune responses.
• Nod like receptor -
• Cytokine receptors: e.g., TNF, IL- 1 receptors on leukocytes and endothelium.
• GPCRs (G protein-coupled receptors): Bind chemokines and lipid mediators.

Signal- transmitting pathways

1. 1 NF- κB Pathway

• Main function:
• Central regulator of inflammation and immune responses.
• What it does:
• Controls transcription of pro-inflammatory cytokines (e.g., TNF- α, IL- 1).
• Induces expression of adhesion molecules (e.g., ICAM- 1, VCAM- 1).
• Promotes production of chemokines and other mediators.
• Activation triggers:
• Pathogen- associated molecules (e.g., LPS via Toll- like receptors).
• Cytokines (e.g., TNF- α).

1. 2 JAK-STAT Pathway

• Main function:
• Mediates cytokine signaling important for immunity, hematopoiesis, and inflammation.