1. 2nd Yr Pathology 2010 Inflammation and cellular responses Prof Orla Sheils

2. 2nd Yr Pathology 2010 Inflammation Is a protective response The body’s response to injury Interwoven with the repair process

3. 2nd Yr Pathology 2010 Inflammation Types Acute (sec, mins, hrs) Chronic (days, weeks, months, yrs)

4. 2nd Yr Pathology 2010 Causes of inflammation Bacterial Viral Protozoal Metazoal Fungal Immunological Tumours Chemicals, toxins etc Radiation

5. 2nd Yr Pathology 2010 Acute inflammation

6. 2nd Yr Pathology 2010 Inflammation The Cardinal Signs of Acute Inflammation RUBOR CALOR TUMOR FUNCTIO LAESA

7. 2nd Yr Pathology 2010 Cardinal signs of inflammation

8. 2nd Yr Pathology 2010 Cardinal signs of inflammation

9. 2nd Yr Pathology 2010 Cardinal signs of inflammation

10. 2nd Yr Pathology 2010 Cardinal signs of inflammation

11. 2nd Yr Pathology 2010 Cardinal signs of inflammation

12. 2nd Yr Pathology 2010 Cardinal signs of inflammation

13. 2nd Yr Pathology 2010 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. 2nd Yr Pathology 2010 Components of acute and chronic inflammation

15. 2nd Yr Pathology 2010 Cell of the acute inflammatory response Polymorphonuclear leukocyte

16. 2nd Yr Pathology 2010 The process of inflammation

17. 2nd Yr Pathology 2010 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. 2nd Yr Pathology 2010 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. The phases of inflammation

19. 2nd Yr Pathology 2010 Local vascular manifestations of acute inflammation

20. 2nd Yr Pathology 2010 Leukocyte migration in inflammation

21. 2nd Yr Pathology 2010 Molecules modulating endothelial-neutrophil interactions LFA-1 and MAC-1 (activated integrins)

22. 2nd Yr Pathology 2010 Acute inflammation: tissue effects Pavementation and diapedesis

23. 2nd Yr Pathology 2010 Acute inflammation: tissue effects Inflammatory cells in protein exudate

24. 2nd Yr Pathology 2010 Acute inflammation: tissue effects Blood vessel involved in the acute inflammatory process

25. 2nd Yr Pathology 2010 Acute inflammation: tissue effects Bronchopneumonia

26. 2nd Yr Pathology 2010 Acute inflammation: tissue effects Abscess: collection of acute inflammatory cells

27. 2nd Yr Pathology 2010 Acute inflammation: tissue effects Multiple splenic abscesses

28. 2nd Yr Pathology 2010 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 Chemical mediators of inflammation

29. 2nd Yr Pathology 2010 Chemical mediators of inflammation PREFORMED Histamine, Serotonin NEWLY SYNTHESISED Prostaglandins Leucotrienes Platelet activating factor Cytokines Nitric oxide LOCAL AND SYSTEMIC

30. 2nd Yr Pathology 2010 Chemical mediators of inflammation (local and systemic)

31. 2nd Yr Pathology 2010 Plasma proteases

32. 2nd Yr Pathology 2010 The complement system

33. 2nd Yr Pathology 2010 Arachidonic acid metabolites HETE = hydroxyeicosatetraenoic acid HPETE = hydroperoxyeicosatetraenoic acid

34. 2nd Yr Pathology 2010 Cytokines (IL-1 and TNF)

35. 2nd Yr Pathology 2010 Nitric oxide (NO)

36. 2nd Yr Pathology 2010 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. 2nd Yr Pathology 2010 Phagocytosis Phagocytosis of bacteria by polymorphs

38. 2nd Yr Pathology 2010 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 H 2 O 2, hypohalous acid (HOC1) produced by myeloperoxidase and superoxides kill bacteria. Lysozyme digests them.

39. 2nd Yr Pathology 2010

40. Chronic inflammation

41. 2nd Yr Pathology 2010 Cells of the chronic inflammatory response Lymphocytes Monocytes/ macrophages Plasma cells

42. 2nd Yr Pathology 2010 Maturation of circulating monocytes to macrophages

43. 2nd Yr Pathology 2010 Macrophage-lymphocyte interactions in chronic inflammation

44. 2nd Yr Pathology 2010 Cellular interactions in chronic inflammation

45. 2nd Yr Pathology 2010 Chronic inflammation: tissue effects Knee joint in rheumatoid arthritis

46. 2nd Yr Pathology 2010 Chronic inflammation: tissue effects Chronic cervicitis

47. 2nd Yr Pathology 2010 Chronic inflammation: tissue effects Lung abscess

48. 2nd Yr Pathology 2010 Granulomatous inflammation: a special form of chronic inflammation

49. 2nd Yr Pathology 2010 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

50. 2nd Yr Pathology 2010 Granulomatous inflammation Bacterial: TB, Leprosy, Syphillis, cat-scratch disease Parasitic: Schistosomiasis Fungal: Histoplasma, blastomycosis, cryptococcus Inorganics, metals, dusts: Silicosis, berrylliosis Foreign body Unknown: Sarcoidosis

51. 2nd Yr Pathology 2010 Granulomatous inflammation: tissue effects

52. 2nd Yr Pathology 2010 Granulomatous inflammation: tissue effects

53. 2nd Yr Pathology 2010 Granulomatous inflammation: tissue effects

54. 2nd Yr Pathology 2010 Granulomatous inflammation: tissue effects Epithelioid cells

55. 2nd Yr Pathology 2010 Granulomatous inflammation: tissue effects Talc granulomas in the lung

56. 2nd Yr Pathology 2010 Healing and repair

57. 2nd Yr Pathology 2010 Wound healing: critical steps

58. 2nd Yr Pathology 2010 The cell cycle

59. 2nd Yr Pathology 2010 Cyclins, cyclin dependent kinases and cyclin dependent kinase inhibitors

60. 2nd Yr Pathology 2010 Cell-cell interactions in repair

61. 2nd Yr Pathology 2010 Cell surface receptors in healing and repair

62. 2nd Yr Pathology 2010 The major components of the extracellular matrix (ECM) required for healing and repair

63. 2nd Yr Pathology 2010 Extracellular matrix re-modelling occurs by the action of Matrix metalloproteinases

64. 2nd Yr Pathology 2010 Matrix metalloproteinase regulation

65. 2nd Yr Pathology 2010 Critical steps in angiogenesis

66. 2nd Yr Pathology 2010 Major growth factors in wound healing

67. 2nd Yr Pathology 2010 Wound healing: critical steps

68. 2nd Yr Pathology 2010 Granulation tissue

69. 2nd Yr Pathology 2010 Granulation tissue

70. 2nd Yr Pathology 2010 Scar tissue Skin

71. 2nd Yr Pathology 2010 Scar tissue Lung

72. 2nd Yr Pathology 2010 Outcome of healing and repair

73. 2nd Yr Pathology 2010 When healing goes wrong Keloid scar