Inflammation

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Inflammation

  1. 1. INFLAMMATION By M. Wasif Zafar
  2. 2. Inflammation: Definition:  Inflammation is a protective response intended to remove injurious stimuli as well as the necrotic cells and tissues resulting from original insert.
  3. 3. ADVANTAGES:
  4. 4. DIS-ADVANTAGES:
  5. 5. PLAYERS OF INFLAMMATION: CIRCULATING CIRCULATING CELLS PROTEINS The inflammatory responses have many players. They include EXTRA VASCULAR CELLULAR WALL CELLS MATRIX
  6. 6. PLAYERS OF INFLAMMATION: 1. CIRCULATING CELLS:  Bone marrow derived polymorph nuclear leukocytes e.g., Basophils, Esinophils and Neutrophils.  Lymphocytes  Monocytes  Platelets.
  7. 7. PLAYERS OF INFLAMMATION: 2. CIRCULATING PROTEINS:  Clotting factors  Kininogens  Complement proteins
  8. 8. PLAYERS OF INFLAMMATION: 3. VASCULAR WALL CELLS:  Connective tissue cells  Smooth muscle cells  Epithelial cells
  9. 9. PLAYERS OF INFLAMMATION: 4. EXTRA CELLULAR MATRIX:  Fibrous structural proteins e.g., Elastin & Fibrinogen  Gel-forming proteoglycans  Adhesive glycoprotein e.g., Fibronectin, that are cell- ECM and ECM-ECM connectors.
  10. 10. PROCESS OF INFLAMMATION: Inflammatory Chemical stimulus mediators When the inflammatory Inflammatory response stimulus is removed these (until mediators are then injurious stimulus is dissipated, catabolized or removed) removed.
  11. 11. TYPES OF INFLAMMATION:
  12. 12. CHRONIC INFLAMMATION: Chronic inflammation is the inflammation with prolonged duration usually from weeks to months and sometimes to years in which active inflammation, tissue injury and healing process proceed simultaneously.
  13. 13. DISTINGUISHING FEATURES:
  14. 14. ORIGIN AND PROCESS: Chronic inflammation arises from acute inflammation. This transition takes place if the acute responses cannot be resolved either because of the persistence e.g., of injurious stimuli or by interference of the normal healing process e.g., peptic ulcer. Some types of injuries engender responses with chronic inflammation initially e.g., viral infections.
  15. 15. SETTINGS LEADING TO CHRONIC INFLAMMATION:
  16. 16. CHRONIC INFLAMMATORY CELLS & MEDIATORS: 1) MACROPHAGES 2) LYMPHOCYTES 3) ESINOPHILS 4) MAST CELLS
  17. 17. CHRONIC INFLAMMATORY CELLS & MEDIATORS: 1) MACROPHAGES: Macrophages are white blood cells within tissues, produced by the division of monocytes. A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of dust is likely to occur. Each type of macrophage, determined by its location, has a specific name:  In liver Kupffer cells  Spleen and lymph nodes Sinus histocytes  Nervous system Microglial cells  Lungs Alveolar macrophages
  18. 18. During chronic inflammation macrophages serve to eliminate injurious agents andinitiate repair- however, they are as well responsible for much of the tissue injurythat occurs Tissue macrophage Activated T cell or NK cell Non Immune activation: IFN-g Endotoxins, fibronectin, chemical mediators Activated macrophage Fibrosis (Scaring) Growth factors involved in fibroblast proliferation (PDGF,TGFb,FGF) Tissue injury Angiogenesis factors Toxic oxygen metabolites (FGF,VEGF) Metallo-proteases Collagen deposition Coagulation factors (IL-13 and TGFb) AA metabolites and NO
  19. 19. CHRONIC INFLAMMATORY CELLS & MEDIATORS: FUNCTIONS OF MACROPHAGES: They help to:  Filter the particulate matter  Kill microbes  Alert immune system of the body.  Their life is 1-2 days.
  20. 20. CHRONIC INFLAMMATORY CELLS & MEDIATORS: ACTIVATION OF MACROPHAGES: Activation of macrophages means:  Increase in size  Increase in lysosomal content  Increase in metabolism  Increase in microbial killing activity
  21. 21. CHRONIC INFLAMMATORY CELLS & MEDIATORS: ACTIVATION SIGNALS: Different signals required to activate macrophages are:  Cytokines produced by T-lymphocytes  Bacterial endotoxins  Different mediators produced during acute inflammation  Extra cellular matrix proteins e.g., Fibrinogen  When macrophages become activated they produce different type of biologically active substances that either cause one of  Cell injury  Fibrosis.
  22. 22. CHRONIC INFLAMMATORY CELLS & MEDIATORS: Cell injury causing substances:  Acid and neutral proteases  Complement proteins C1 to C5  Coagulating factors V & VШ  Amino acids metabolites  Cytokines  Tumor necrosis factor
  23. 23. CHRONIC INFLAMMATORY CELLS & MEDIATORS: Fibrosis causing substances:  Growth factors  Fibrogenic cytokines  Angiogenesis factors  Regeneration and remodeling factors
  24. 24. CHRONIC INFLAMMATORY CELLS & MEDIATORS: 2) LYMPHOCYTES: Both T- & B-lymphocytes are involved in chronic inflammation. Their migration is brought about by specific adhesion molecules and cytokines. The T- lymphocytes work in reciprocal with B-lymphocytes in chronic inflammation. The already activated macrophages release TNF & IL1 and activate the inactive lymphocytes which then produce different antibodies that cause destruction of antigens at the inflammatory site.
  25. 25. CHRONIC INFLAMMATORY CELLS & MEDIATORS: 3) ESINOPHILS: They are usually found in parasitic infections and IgE mediated allergic reactions. Their migration is brought about by adhesion molecules produced by leukocytes and epithelial cells. Esinophils specific granules contain Major Basic Proteins which is highly cationic &toxic for parasites.
  26. 26. CHRONIC INFLAMMATORY CELLS & MEDIATORS: 4) MAST CELLS: Mast cells are tissue cells which are like basophils in shape. They are present in bone marrow and around blood vessels and do not enter the blood. They are specifically armed with IgE antibodies against certain antigens. When these antigens are encountered, they release histamines and amino acid metabolites. They cause initial vascular changes in acute inflammation and also cause anaphylactic reactions.
  27. 27. TYPES OF CHRONIC INFLAMMATION:
  28. 28. TYPES OF CHRONIC INFLAMMATION: 1) AGRANULOMATOUS: Granuloma is not formed, Inflammation is characterized by all features of chronic inflammation. Examples:  Chronic viral infections e.g., Hepatitis  Chronic autoimmune diseases e.g., Rheumatoid arthritis and Ulcerative colitis  Chronic chemical intoxication e.g., Chronic alcoholic liver disease  Allergic reactions e.g., Bronchial asthma
  29. 29. TYPES OF CHRONIC INFLAMMATION: 2) GRANULOMATOUS INFLAMMATION: Characterized by aggregates of activated macrophages that assume a squamous cell like epithelloid appearance. GRANULOMA is defined as aggregates of macrophages formed due persistant response of T-lymphocytes to particular antigens. This has a granular cheesy appearance called as caseous necrosis.
  30. 30. TYPES OF CHRONIC INFLAMMATION:Examples are:Bacterial: Tuberculosis , Leprosy, Syphilis gumma etc.Parasitic: SchistosomiasisFungal: Histoplasma capsulatum, Blastomycosis.Inorganic metals / Dust: SilicosisForeign bodies: Suture, Vascular graft.Unknown: Sarcodiosis.

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