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Cell Injury and Inflammation

Cell Injury and Inflammation. Reference: Robbins Basic Pathology 7 th edition. Kumar, Cotran, Robbins editors. 2003. Immunology, 6 th edition. Roitt, Brostoff, Male. 2001 Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005

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Cell Injury and Inflammation

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  1. Cell Injury and Inflammation Reference: Robbins Basic Pathology 7th edition. Kumar, Cotran, Robbins editors. 2003. Immunology, 6th edition. Roitt, Brostoff, Male. 2001 Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 Internet. Accessed November 30, 2007

  2. Cell Injury a

  3. Cell changes a

  4. Free radical generation a

  5. Cellular injury types a

  6. Apoptosis a

  7. Apoptosis inhibitors d

  8. Pathogens Virus Bacteria Fungi Protozoa Multicellular parasites Protection Skin Mucosal epithelium Secretions, tears Physical Rapid air flow Peristalsis Ciliary movements pH Commensals Pathogens and body defenses

  9. nucleus • oxygen • macronutrients • micronutrients • substrates • hormones • cytokines • CO2 • breakdown products • micronutrients • substrates • hormones • cytokines • energy production • substrate utilization • substrate synthesis • protein / complex subs synthesis LOCAL EFFECTS Endothelium interaction • Interaction with clotting mechanism • interaction with inflammation process SYSTEMIC EFFECTS Capillary arterial side Capillary venous side The microcirculatory environment

  10. Normal environment a

  11. Inflammatory mediators a

  12. Inflammation b

  13. Inflammation a

  14. Capillary environment a

  15. Kinin/clotting/complement system a

  16. Complement system a

  17. Eicosanoids a

  18. Cells-cell interaction and eicosanoids a

  19. Calder Philip, Polyunsaturated fatty acids, inflammation, and immunity : Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 EPA NFB Arachidonic acid in membrane phospholipids DHA Phospholipase A2 Inflammatory effects (e.g. cytokines) Free arachidonic acid COX-2 5-LOX 5-LOX COX-2 COX-2 E-series resolvins 3-series PG & TX 5-series LT 2-series PG & TX 4-series LT D-series resolvins, etc Anti Inflammatory effects Inflammatory effects Less Inflammatory effects than 4-series Less Inflammatory effects than 2-series Anti Inflammatory effects Anti Inflammatory effects Inflammatory effects -3 PUFA c

  20. Inflammation a

  21. Local activity a

  22. Neutrophil actions a

  23. Activated leucocyte a

  24. Leucocyte mechanisms a

  25. Cytokines a

  26. B cell CTL NK Cell Th1 Naive Th cell Th0 Th2 Current update B Cell

  27. Interleukins d

  28. Interleukins d

  29. Interleukins d

  30. Inflammation Outcomes a

  31. Histopath a

  32. Nitric Oxide a

  33. L-arginine Plasma membrane L-arginine ASL O2 NADPH+ + H AS GTP BH4 NOS Ca2+ ASS NADP+ L-citrulline Nitric oxide Wu and Meininger, 2002, Annu Rev Nutr. 22: 61-68 Flynn et al, 2005, Nutrients and Signalling 225-252 Nitric oxide b

  34. Wu G, Nutritional regulations of NO synthesis and its implications for health; : Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 Fe, cobalt, nickel macrophages ceramide Vitamin A & D3 LDL & linoleic acid ginseng High fat diet islets, liver, colon glutamine arginine copper Arteries, aorta, vascular smooth muscle cells Fructose Fe Phytanic acid polyphenols Brain, heart, Retinal cells kidney Inducible NOS: activity b

  35. Wu G, Nutritional regulations of NO synthesis and its implications for health; : Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 3 & 6 PUFA Cd, Cr, Cu, Lead macrophages polyphenols fructose carotenoids High ethanol Lung, GIT glucosamine glutamine Taurine Lysine endothelial cells, vascular smooth muscle cells Niacin & B6 High glucose Vit A, D3, & E Iron kidney High salt diet neuronal cells Fructose Melatonin & Vit D3 Inducible NOS: activity b

  36. Inflammation outcomes a

  37. Histopath a

  38. Monocytes a

  39. Tissue inflammation, Early organ failure and death SIRS TNF, IL-1, IL-6, IL-12, IFN, IL-3 Immunonutrients PRO glutamine days weeks Inflammatory balance ANTI IL-10, IL-4, IL-1ra, Monocyte HLA-DR suppression Immunosuppression Delayed MOF and death 2nd Infections CARS Insult (trauma, sepsis) Griffiths, R. “Specialized nutrition support in the critically ill: For whom and when? Clinical Nutrition: Early Intervention; Nestle Nutrition Workshop Series Inflammation and organ failure in the ICU

  40. Lecuit M, Sonnenburg J. Host-microbial relationship in the intestine: sensing commensal and pathogenic bacteria: Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005 Host-microbial interaction c

  41. Gut – inductive and effector sites c Per Brandtzaeg, Mucosal adaptive immunity: impact of exogenous stimuli and feeding; Nutrition, immune functions and health; Euroconferences, Paris; June 9-10, 2005

  42. Cytotoxic T cells macrophages

  43. macrophages Ligands (glycoproteins) Cytotoxic T cells

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