Week 6

• Outcomes of Acute Inflammation:

  • Inflammation of prolonged duration (usually weeks) in which active inflammation, tissue destruction, and attempts at repair occur simultaneously
• Persistent Stimulus for Chronic Inflammation:

  • Gastric ulcer
  • Persistent infection like Mycobacteria tuberculosis, certain viruses, or parasites
  • Prolonged exposure to toxic agents like non-degradable silica, coal dust
  • Lipid breakdown products in atherosclerosis
  • Autoimmunity like Rheumatoid arthritis
• Characteristics of Chronic Inflammation:

  • Infiltration with mononuclear cells (macrophages, lymphocytes, and plasma cells)
  • Tissue destruction
  • Healing
  • Replacement of damaged tissue with fibrosis
• Cellular mediators of Chronic Inflammation - Macrophages:

  • Activated by cytokines (IFN), bacterial endotoxins, and other chemical mediators
  • Mediate tissue injury and fibrosis
• Cellular mediators of Chronic Inflammation - Lymphocytes:

  • B and T cells
  • Major role in both antibody-mediated and cell-mediated immune reactions
• Cellular mediators of Chronic Inflammation - Plasma cells:

  • Develop from activated B cells
  • Secrete antibodies
• Cellular mediators of Chronic Inflammation - Eosinophils:

  • Particularly involved in parasite infections
• Cellular mediators of Chronic Inflammation - Mast Cells:

  • Bind to Fc part of IgE
  • Degranulate to release histamine
  • Seen in food allergies, drug reactions
• Gastric Ulcer:

  • Caused by persistent damage to the stomach lining (e.g., acid)
  • Features acute inflammation, tissue damage, and healing with fibrosis
• Role of H. Pylori in Gastric Ulcer:

  • Present in all patients with duodenal ulcers and 70% of patients with gastric ulcers
  • Induces inflammatory response by stimulating release of cytokines (IL-8) and causes direct epithelial cell damage
• Chronic Systemic Inflammatory Disease:

  • Affects multiple tissues and organs like joints, skin, eyes, and blood vessels
  • Affects 1% of the world population with a female to male ratio of 3:1
  • Example: Rheumatoid Arthritis
• Rheumatoid Arthritis:

  • Lining of joint (synovium) infiltrated by lymphocytes, macrophages, plasma cells
  • Cutaneous Rheumatoid nodules have a central zone of necrosis surrounded by a rim of epithelioid macrophages
• Rheumatoid Arthritis Pathogenesis:

  • Autoimmune disease triggered by exposure of genetically susceptible individuals to antigen
  • The autoimmune response leads to an inflammatory reaction releasing mediators causing tissue destruction, with key mediators being IL-1 and TNFa
• Granulomatous Disease is a specific type of chronic inflammation characterized by the accumulation of activated macrophages that become epithelioid
• A granuloma is a focus of chronic inflammation consisting of an aggregate of macrophages transformed into epithelioid cells surrounded by lymphocytes and plasma cells
• There are two types of granulomas: Foreign body type and Immune type
• Foreign-body type granulomas are due to the ingestion of material by macrophages that cannot be destroyed
• Immune type granulomas are generated by insoluble fragments (usually micro-organisms) that cause a cell-mediated immune reaction
• Immune type granulomas are examined through 'crossed polaroids'
• Causes of Granulomatous Inflammation include mycobacterium tuberculosis, persistent infections like Mycobacteria, syphilis, leprosy, autoimmune diseases like Crohn’s disease, and diseases of unknown etiology like Sarcoidosis
• Tuberculosis is caused by mycobacterium tuberculosis and can lead to the formation of Ghon focus in the initial infection stage and Ghon complex when it spreads to hilar lymph nodes
• In pulmonary tuberculosis, the early phase shows granuloma with caseous necrosis, which can be identified using the Ziehl-Nielsen Stain for acid-fast bacteria
• Major complications of tuberculosis include tissue destruction, effects of repair, and fibrosis
• In adult tissue, the size of a cell population is determined by proliferation, apoptosis, and differentiation
• Stem cells are characterized by capacity and asymmetric division, including self-renewal and differentiation
• Embryonic stem cells are pluripotent stem cells that give rise to all cells in the body and have therapeutic potential for tissue regeneration
• Adult stem cells can be multipotent (e.g., haematopoietic stem cells, bone marrow stromal cells) or unipotent (e.g., gut, skin)
• Haematopoietic stem cells can differentiate into hepatocytes for liver regeneration, raising the question of stem cells' transdifferentiation ability
• Cell proliferation is regulated by growth factors, hormones, and cell-matrix interactions
• Growth factors like Epidermal Growth Factor, Fibroblast Growth Factor, Keratinocyte Growth Factor, and Transforming Growth Factor play roles in proliferation, locomotion, differentiation, and angiogenesis
• Specific growth factors like EGF and TGF beta have distinct actions in promoting cell growth and inhibiting proliferation of epithelial cells while stimulating fibroblasts