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Inflammation and cellular responses Prof Orla Sheils

Inflammation and cellular responses Prof Orla Sheils. Inflammation. Is a protective response The body’s response to injury Interwoven with the repair process. Inflammation. Types Acute (sec, mins, hrs) Chronic (days, weeks, months, yrs). Causes of inflammation. Bacterial Viral

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Inflammation and cellular responses Prof Orla Sheils

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  1. Inflammation and cellular responses Prof Orla Sheils

  2. Inflammation • Is a protective response • The body’s response to injury • Interwoven with the repair process

  3. Inflammation • Types • Acute (sec, mins, hrs) • Chronic (days, weeks, months, yrs)

  4. Causes of inflammation • Bacterial • Viral • Protozoal • Metazoal • Fungal • Immunological • Tumours • Chemicals, toxins etc • Radiation

  5. Acute inflammation

  6. Inflammation • The Cardinal Signs of Acute Inflammation RUBOR CALOR TUMOR FUNCTIO LAESA

  7. Cardinal signs of inflammation

  8. Cardinal signs of inflammation

  9. Cardinal signs of inflammation

  10. Cardinal signs of inflammation

  11. Cardinal signs of inflammation

  12. Cardinal signs of inflammation

  13. Inflammation The basis of the five cardinal signs • Increased blood flow due to vascular dilatation gives redness and heat. • Increased vascular permeability gives oedema causing tissue swelling. • Certain chemical mediators stimulate sensory nerve endings giving pain. Nerves also stimulated by stretching from oedema. • Pain and swelling result in loss of function.

  14. Components of acute and chronic inflammation

  15. Cell of the acute inflammatory response • Polymorphonuclear leukocyte

  16. The process of inflammation

  17. The phases of inflammation • FIRST THERE IS VASCULAR DILATATION followed by exudation of protein-rich oedema fluid which floods the area, dilutes toxins, allows immunoglobulins to opsonise bacteria and provides substrate (fibrinogen) for fibrin scaffold. • SECOND THERE IS ACTIVE EMIGRATION OF POLYMORPHS through vessel wall and along the chemotactic gradient to the site of injury

  18. The phases of inflammation • THE VASCULAR PHASE OF INFLAMMATION Fluid escapes from vessels because of endothelial cell (EC) retraction, opening up gap-junctions. The vessels which are normally involved are the post-capillary venules where the EC have high affinity receptors for histamine. Severe EC injury leads to leakiness of all vessels capillaries, venules and arterioles - giving acute local oedema, e.g. blister formation after a burn.

  19. Local vascular manifestations of acute inflammation

  20. Leukocyte migration in inflammation

  21. Molecules modulating endothelial-neutrophil interactions LFA-1 and MAC-1 (activated integrins)

  22. Acute inflammation: tissue effects Pavementation and diapedesis

  23. Acute inflammation: tissue effects Inflammatory cells in protein exudate

  24. Acute inflammation: tissue effects Blood vessel involved in the acute inflammatory process

  25. Acute inflammation: tissue effects Bronchopneumonia

  26. Acute inflammation: tissue effects Abscess: collection of acute inflammatory cells

  27. Acute inflammation: tissue effects Multiple splenic abscesses

  28. Chemical mediators of inflammation • Vasoactive amines • Histamine • Serotonin (5-HT) • Neuropeptides • Substance P • Plasma proteases and the complement system • Action of Hageman factor • Arachidonic acid metabolites • Prostaglandins • Leukotrienes • Lipoxins • Cytokines • IL-1, TNF etc. • Chemokines (CXC and CC) • Nitric oxide and oxygen-derived free radicals

  29. Chemical mediators of inflammation • PREFORMED Histamine, Serotonin • NEWLY SYNTHESISED Prostaglandins Leucotrienes Platelet activating factor Cytokines Nitric oxide • LOCAL AND SYSTEMIC

  30. Chemical mediators of inflammation (local and systemic)

  31. Plasma proteases

  32. The complement system

  33. Arachidonic acid metabolites HETE = hydroxyeicosatetraenoic acid HPETE = hydroperoxyeicosatetraenoic acid

  34. Cytokines (IL-1 and TNF)

  35. Nitric oxide (NO)

  36. Effects of mediators of inflammation Vasodilation: Prostaglandins, NO Increased vascular permeability: Histamine, serotonin, C3a, C5a, bradykinin, Leukotrienes C4, D4, E4, platelet activating factor Chemotaxis, leukocyte activation: C5a, leukotriene B4, bacterial products, chemokines (IL-8) Fever: IL-1, IL-6, TNF, prostaglandins Pain: Prostaglandins, bradykinin Tissue damage: Neutrophil and macrophage lysosomal enzymes, oxygen metabolites NO

  37. Phagocytosis Phagocytosis of bacteria by polymorphs

  38. PHAGOCYTOSIS Recognition and attachment Foreign objects coated with opsonins IgG and C3b which attach to receptors on polymorph surface. Engulfment Cell membrane fuses around an object: at the some time lysosomes empty into the vacuole, often before vacuole has time to seal - this gives rise to 'regurgitation during feeding' and enzymatic damage to surrounding tissue. Killing or degradation H2O2, hypohalous acid (HOC1) produced by myeloperoxidase and superoxides kill bacteria. Lysozyme digests them.

  39. Chronic inflammation

  40. Cells of the chronic inflammatory response • Lymphocytes • Monocytes/ macrophages • Plasma cells

  41. Maturation of circulating monocytes to macrophages

  42. Macrophage-lymphocyte interactions in chronic inflammation

  43. Cellular interactions in chronic inflammation

  44. Chronic inflammation: tissue effects Knee joint in rheumatoid arthritis

  45. Chronic inflammation: tissue effects Chronic cervicitis

  46. Chronic inflammation: tissue effects Lung abscess

  47. Granulomatous inflammation:a special form of chronic inflammation

  48. Granuloma • Definition • A collection of macrophages, lymphocytes, mononuclear cells and fibroblasts with or without giant cell formation and constitutes a special form of chronic inflammation

  49. Granulomatous inflammation Bacterial: TB, Leprosy, Syphillis, cat-scratch disease Parasitic: Schistosomiasis Fungal: Histoplasma, blastomycosis, cryptococcus Inorganics, metals, dusts: Silicosis, berrylliosis Foreign body Unknown: Sarcoidosis

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