The Immunological Response to Injury, Sepsis, and Chronic Inflammatory Illness 2020 Part 1 PDF

Department of Neuroscience, Physiology & Pharmacology University College London The immunological response in injury, sepsis and chronic inflammatory diseases Dr Dean Willis [email protected] Lecture Content in 3 parts The concept of physiological and pathological in...

Department of Neuroscience, Physiology & Pharmacology University College London The immunological response in injury, sepsis and chronic inflammatory diseases Dr Dean Willis [email protected] Lecture Content in 3 parts The concept of physiological and pathological inflammation Part 1 Basic pathways in vascular inflammation, innate & adaptive pathways* Part 2 Sepsis & chronic inflammation Part 3 Concept of meta-inflammation (low grade inflammation) Dysfunctional Inflammation (un-controlled) Acute Chronic Contributory Why should nutritionist be interested in inflammation? An anti-inflammatory diet as a potential intervention for depressive disorders: A systematic review and meta- analysis. Clinical Nutrition 38:2045-2052 (2019) The Basics Inflammation “Inflammation is a salutary process” Treatise on the blood, Inflammation and Gun-shot Wounds. John Hunter 1794 Kill Dilute Wall-off Prepare Dysfunctional Inflammation (to little) Primary immunodeficiency Acquired immunodeficiency Cardinal Signs of inflammation Inflammation Innate Response Sentinel Activation Vascular Dilatation Increased Blood flow New Stimulus Increase Permeability Damage Excessive inflammation Infection Tissue necrosis Trauma (Physical & chemical) Autoimmunity Hypersensitivity reactions Neoplasm Leukocyte migration Continued inflammation Resolution Effect phase Lymphocyte recruitment Cellular/tissue activation Cellular Anti-microbial Leukocyte migration Phagocytosis Antigen presentation Induction phase Antigen presentation Clonal expansion & maturation Specific/adaptive Response Inflammation Outputs Principals for immunity/inflammation from a systems biology ROBUST RESPONSE Appropriate Redundancy Responsive Networks Cascades Modular Complexity Stochastic resonance Feedback Pleiotropic Energy Buffering Fragile Inflammatory Mediators, Human Pharmacology Wheal and Flair reaction (Lewis triple response) Cellular components of inflammation Mast cells Resident cells, activated by IgE and complement release Histamine, leukotrienes, protaglandins, PAF, interleukins (IL- 4,5 & 6) Neutrophils First cells to migrate (ICAM-1), Phagocytosis and kill opsonizied bacteria (C3b, CD14 receptors for endotoxins) Release leukotrienes, protaglandins free radicals, interleukins (IL-1 & TNFa) & proteases Eosinophils Similar to neutrophils however have more granules. Have a role in parasitic infections and in late phase asthma & allergic inflammation. Release leukotrienes, protaglandins, interleukins (1,5,6,8 & TNFa) & proteases Macrophages Antigen presentation, Microbe killing, Granuloma formation, innate inflammation , Angiogenesis, Wound healing Lymphocytes Divided into B and T (subdivided into CD4+ and CD8+) cells involved in immune mediated inflammation Neurons Neurogenic inflammation, release neuropeptides Activated by Bradykinin and 5-HT Platelets Involved in coagulation, have low affinity IgE receptors Release PAF Thromboxane A (some) Inflammatory Mediators Heat Histamine PGE2 (calor) 5-hydroxytryptamine PGI2 Increased blood flow Platelet Activating Factor Redness Nitric oxide (rubor) Bradykinin Anaphylatoxins C3a C5a Swelling Increased vascular permeability LTB4 TNFa & IL-1 (tumor) Cellular infiltration PGE2 IL-8 VEGF PGE2 Platelet Activating Factor Bradykinin Substance P Pain Calcitonin gene-related peptide (dolor) Bradykinin Lipases Loss of Function Proteases (functio laesa) Free radicals Note this can also be modification e.g. spasm of bronchial muscle Bradykinin LTD4 LTC4 Histamine