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• The Immune System Major Sub-Divisions

  • IMMUNE SYSTEM
  • INNATE IMMUNE SYSTEM
  • ADAPTIVE IMMUNE SYSTEM
• Innate Immune System


  Non-specific, Immediate (Minutes), First line of defence, No Memory
• Adaptive Immune System


  Specific, Slow, requires days to act, Second line of defence, Has immunological memory
• Invaders


  • Macrophage
  • B-Cell
• Inflammation is a protective reaction of vascularised living tissue to local injury
• Inflammation is a protective response of vascularised tissues to infections and damaged tissues that brings cells and molecules of host defence from the circulation to the sites where they are needed, in order to eliminate the offending agents
• Inflammation serves to destroy, dilute or isolate the injurious agent (microbes, toxins), as well as eliminate the necrotic cells and tissues resulting from the original insult
• Inflammation starts a series of events which leads as far as possible to the healing and reconstitution of the damaged tissue
• Steps of the Inflammatory Response

  1. Recognition of the offending agent / injury

  2. Recruitment of Leukocytes

  3. Removal of the offending substance

  4. Regulation (Control) of the Response

  5. Repair of the damaged tissue
• Acute Inflammation


  Rapid Onset (minutes / hours), Short Duration (minutes, several hours, few days), Mainly Neutrophils, Prominent Characteristic Response
• Chronic Inflammation


  Slow Onset (days), Long Duration (days, weeks, months), Monocytes / Macrophages / Lymphocytes, Less Characteristic Response
• Cardinal Signs of Inflammation

  • Redness (rubor)
  • Heat (calor)
  • Swelling (tumor)
  • Pain (dolor)
  • Loss of Function
• Acute Inflammation has 3 major components

  1. Vascular

  2. Cellular
• Key Inflammatory Mediators

  • Histamine
  • Mast Cell
  • Basophil
  • Prostaglandins
  • Leukotrienes
  • Cytokines
  • Chemokines
• 2 Main Cellular Mediator of Chronic Inflammation

  • Macrophage
  • Lymphocyte
• Macrophage


  Phagocytosis, Initiate tissue repair, Secrete Cytokines/ Chemokines
• Lymphocyte


  Lymphocyte activation, Propagate Chronic Inflammation, Secrete Antibodies, Via Antigen presentation
• Drug classes to reduce inflammatory and immune responses

  • Anti-cytokine drugs & other biologicals
  • Immunosuppressants
  • Disease modifying anti-rheumatoid drugs (DMARD)
  • Steroidal anti-inflammatory agents
  • Nonsteroidal anti-inflammatory agents (NSAID)
  • Anti-histamines
• Drug classes to modulate inflammatory and immune responses

  • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
  • Steroidal Anti-inflammatory Drugs
  • Anti-Histamines and Hypersensitivity Type 1 Drugs
  • Immunosuppressant Drugs
  • Immune Check Point Inhibitors
• Signalling Pattern Recognition Receptors (PRR)
• Toll Like Receptor

  PAMP, Activates transcription NFKB & IRF 3/7, Secretion of Cytokines, Inflammation
• DAMP

  Damage-associated molecular patterns, STRANGER DANGER, Damaged Cell
• COX-2


  Induced upon inflammatory cell activation
• COX-1


  Housekeeper, performs many roles, expressed widely
• Unwanted responses ('side effects') thought to be exerted mainly through COX-1 isoform inhibition
• Anti-inflammatory, analgesic & antipyretic activity of NSAIDs thought to be exerted mainly by COX-2 isoform inhibition
• Clinical Use of NSAIDs

  • Anti-inflammatory
  • Anti-inflammatory in chronic inflammation
  • Analgesia
  • Anti-pyretic
  • Anti-thrombotic
• Paracetamol not an NSAID, little anti-inflammatory action, but used in similar scenarios
• NSAID Mechanism of Action


  1. Cyclo-oxygenase INHIBITION

  2. Arachidonic acid

  3. Prostanoids

  4. Several mechanisms
• Symptoms of inflammation are mediate by COX-2 and the side effects from non-selective NSAIDs are mediated by COX-1
• Systemic Effects of Inflammation

  1. Fever – Pyrexia

  2. Pyrogens

  3. Secretion of Cytokines into Blood Stream

  4. Migrate to the Brain

  5. Bind receptors on Brain Endothelial Cells

  6. Activates Prostaglandin E2 Synthesis

  7. Hypothalamus
• Why pyrogens induce fever
• NSAIDs adverse effects - COX1

  • Gastrointestinal
  • Renal Effects
  • Skin Rashes
  • Bronchospasm
• If the symptoms of inflammation are mediate by COX-2 and the side effects from non-selective NSAIDs are mediated by COX-1, why not just inhibit COX-2?
• NSAIDs COXIB's - Heart: COX2 only, Specific COX2 inhibitors risk of thrombotic events, heart attack, Stroke with prolonged use
• In placebo comparisons, selective COX 2 inhibitors associated with a 42% relative increase in the incidence of serious vascular events
• NSAIDs adverse effects - cardiovascular


  1. Arachidonic acid

  2. Endothelial cell

  3. Platelet
• Balance Theory. Imbalance in anti- and pro-thrombotic prostanoids
• Lipocortin


  Cortisol Anti-inflammatory Effects
• Hypersensitivity reactions are exaggerated or inappropriate immunologic responses occurring in response to an antigen or allergen