L6 Chronic Inflammation

• Acute inflammation


  Mainly neutrophils, asymptomatic/short duration
• Chronic inflammation


  Repeated re-injury and healing, release of proteases/ROS/NO, complement activation, tissue damage, fibroblast/endothelial proliferation, ECM, angiogenesis, granulation tissue, fibrosis, loss of function
• Chronic inflammatory cycle


  1. Inflammatory cells in tissue

  2. Tissue destruction

  3. Connective tissue deposition
• Chronic inflammation


  • Inflammatory cell infiltrate (macrophages, lymphocytes, plasma cells)
  • Tissue destruction
  • Connective tissue deposition
• Chronic inflammation is the cause of the most common disabling diseases such as RA, atherosclerosis, TB etc
• Chronic inflammation


  Prolonged response to persistent stimuli (infections, immune-mediated diseases, prolonged exposure to toxic agents)
• Granulomatous inflammation


  Distinct pattern of chronic inflammation, attempt to contain an offending agent, necrotic centre surrounded by macrophages/epithelioid cells/lymphocytes, epithelioid/giant cells are types of macrophages
• Raised CRP and acute phase reactants in the blood (such as Serum Amyloid A) are markers that can be used to monitor chronic inflammatory disease
• Chronically raised inflammatory cytokines can promote heart disease
• Hypersensitivity reactions


  • Antibody mediated (Type I, II, III)
  • Cell mediated (Type IV)
• Immediate (Type I) hypersensitivity

  1. B cells produce IgE antibodies which stick to mast cells

  2. Second exposure leads to IgE cross-linking and mast cell degranulation
• Type II hypersensitivity


  1. Antibody mediated opsonisation

  2. Antibody fixes complement inducing inflammation

  3. Antibodies mimic ligands, can stimulate or block receptors and lead to faulty signalling
• Type III hypersensitivity


  1. Antibodies bind to soluble antigen in blood and form immune complexes

  2. Aggregates deposit in blood vessel walls, fix complement and resist phagocytosis (vasculitis)

  3. Results in inflammation leading to fibrinoid necrosis

  4. Sites where blood is filtered like kidneys are particularly affected

  
• Type IV hypersensitivity


  1. Activated T lymphocytes release cytokines which activate macrophages

  2. Macrophages and lymphocytes induce tissue injury

  3. Formation of granuloma is a common response to persistent/non-degradable antigens

  4. Alternately CTLs attack tissue

  
• Type I hypersensitivity reactions

  Occur when IgE antibodies bind to mast cells or basophils, causing the release of histamine and other inflammatory mediators. Examples include anaphylaxis and allergic rhinitis.
• Type II hypersensitivity reactions

  Occur when antibodies bind to antigens on the surface of cells, causing complement activation and cell lysis. Examples include autoimmune hemolytic anemia and Goodpasture's syndrome.
• Type III hypersensitivity reactions

  Occur when antigen-antibody complexes deposit in tissues, causing complement activation and inflammation. Examples include serum sickness and systemic lupus erythematosus (SLE).
• Type IV hypersensitivity reactions

  Occur when T cells recognize and respond to antigens presented by antigen-presenting cells (APCs), causing the release of cytokines and the activation of macrophages. Examples include contact dermatitis and tuberculosis.