1. Tutorial 1 Inflammation and cellular responses

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

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. The process of inflammation

15. Components of acute and chronic inflammation

16. Local manifestations of acute inflammation

17. Leukocyte migration in inflammation

18. Molecules modulating endothelial-neutrophil interactions

19. Chemical mediators of inflammation (local and systemic)

20. Plasma proteases

21. The complement system

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

23. Cytokines (IL-1 and TNF)

24. Nitric oxide (NO)

25. Effects of inflammation and their major mediators Vasodilation: Prostaglandins, NO Increased vascular permeability: Histamine, serotonin, C3a, C5a, bradykinin, Leukotrienes C4, D4, E4, platelet activating factor Chemotaxis, leukocyte activation: C5a, lekotriene 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

26. Chronic inflammation

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

28. Maturation of circulating monocytes to macrophages

29. Macrophage-lymphocyte interactions in chronic inflammation

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

31. Granulomatous inflammation: tissue effects

32. Healing and repair

33. The cell cycle

34. The major components of the extracellular matrix (ECM) required for healing and repair

35. Major growth factors in wound healing

36. Critical steps in angiogenesis

37. Wound healing: critical steps

38. Outcome of healing and repair