Inflammatory Response Acute GN PDF

Inflammatory Responses Part 1 Sarah Balian Biomedical Science Intended Learning Outcomes By the end of this session students should be able to: Describe the classical signs of acute inflammation and their relevance. Explain significance of the formation of a cellular and a fluid exudate and...

Inflammatory Responses Part 1 Sarah Balian Biomedical Science Intended Learning Outcomes By the end of this session students should be able to: Describe the classical signs of acute inflammation and their relevance. Explain significance of the formation of a cellular and a fluid exudate and how they are formed. Discuss the assorted ways by which acute inflammation can be generated. Explain the processes of phagocytosis and bacterial killing. Recognise the effects and action of chemical mediators involved with acute inflammation on tissues. Inflammation Tries to protect the body Has negative impact on body in lots of different ways What does inflammation mean to you? Purpose? Armed with your writing utensils Friend or Foe? Jot down bullet points to the following questions What does it ‘look’ like? Relevance of inflammation in dentistry? Periodontal disease Define Inflammation What key words would you use? Response to trauma or something that’s happened to tissue (soft tissue) Local response of tissue to injury Stimulus can be variable: 1. Microbial 2. Immunological 3. Physical 4. Chemical agents Will inflammation & its chemicals really stay local? No - circulates the body Types of Inflammation Inflammation Acute Chronic Quick response, short duration Inflammation Inflammation Long standing Features comparing Acute & Chronic Inflammation Feature Acute Chronic Onset Fast Slow Cellular infiltrate Mainly neutrophils Monocytes/macrophages & lymphocytes Tissue injury / fibrosis Usually mild and self-limited Local & systemic factors Prominent Presence of cardinal signs Likely to be present No cardinal signs Presence of stimulus Long term exposure Response Fibrosis & angiogenesis  Acute Infections Tissue necrosis Bacteria, viruses, fungi, Physical / chemical injuries parasites Heart attack Collection of dead tissue in confined space Trauma Foreign bodies Blunt & penetrating trauma Splinters, sutures, bones, Burns, frostbite, chemicals finger nails Popcorn kernels Immune (hypersensitivity reactions) Triggered by environmental factors Or autoimmune diseases Cardinal Signs of Acute Inflammation Five Cardinal Signs of Inflammation Rubor (redness) Calor (heat) Tumor (swelling) Dolor (pain) Loss of function Event in Acute Inflammation Linked with Immunology Lectures  Events Changes in the blood vessels Vascular Events Redness occurs when blood vessels dilate (get bigger) - to try and get more white blood cells to injury 1. Persistent vasodilation Increase in pressure in vessels 2. Elevation of hydrostatic pressure Allow more in and more out 3. Increase in vascular permeability 4. Transudation of fluid into Fluid released when there is a lot of hydrostatic pressure extracellular space 5. Slowing of or statis of micro circulation Speed of flow slows down Gives time for neutrophils  More in and more out Causes of increased vascular permeability Endothelial cell contraction Endothelial injury 1. Direct 2. Leucocyte induced Increased transcytosis fluid Leakage from new blood vessels Image from Researchgate Feb 2021 Injury to endothelial cells White blood cells trying to break through Transudatic fluid trying to force through  Leucocyte recruitment to site – Cellular Events chemotaxsis Calling of white blood cells to the site of injury/trauma/insult through chemical gradient and chemical messengers. Phagocytosis of particles – engulfment of particles Chemokine - chemical messengers Concentration gets higher as gets closer to injury  Chase and engulf the insult Phagocytosis 2 types of phagocytic cells 1. PMN’s part of early inflammatory response 2. Monocytes & macrophages Opsonisation – ‘marker’ Coating of antigen Tissues mark antigens to become engulfed  Neutrophils and macrophages Phagocytosis when at inflamed tissue site Bacteria - gingivitis - redness - inflammation - vasodilation has occurred- chemokines have been sent out to get more white blood release proteolytic enzymes: cells - white blood cells joined and released enzymes - breaks down collagen White blood cells also release enzymes as well as phagocytose or send out antibodies Protease Collagenase Elastase Lipase So the ‘host’ is calling upon the immune cells to ‘come and fight’ against an ‘insult’. The immune response arrives however as well as impacting the ‘insult’, who else is it impacting? The host Patterns of Inflammation Suppurative Serous Fibrinous Ulcerative (purulent) Big leakage - body cavities or cancers Pus - necrotic tissue - Break in surface of epithelial tissue/lining Blister/fluid dead body cells and PMNs and leukocytes sit at margins bacteria trying to fight and prevent further infection. Can become chronic if long standing. Chemical Mediators Image from Nature Feb 2021 18  Chemical Mediators – a chemical messenger that acts upon a blood vessel, inflammatory cells or other cells to cause a inflammatory response They need a trigger - usually a blood vessel Exogenous Endogenous Endotoxins Insult might be microbial - endotoxins might end up creating response Plasma Coming from where? Bacteria Leucocytes Endothelial cells Coming from body - host Fibroblasts - these cells send out chemical mediators to call upon more cells and help. Image from pinterest website Feb 2021 Chemical Mediators - CYTOKINES They make a certain set of events to call upon other cells Chemical proteins produced by many These all make the chemical messenger to set a series of events to cells I call different cells. E.g. Produced by PMN’s 1. Macrophages 2. B Lymphocytes 3. Epithelial cells 4. Gingival Fibroblasts 5. Osteoblasts Mediate & regulate immune & inflammatory reactions  Want to cause further inflammation Want to reduce inflammation Cytokines – be pro-inflammatory & anti- inflammatory Interleukin (IL-1, IL-6 & IL-8) Tumor Necrosis Factor (TNF) Produced by leucocytes & many Immune cell recruitment, other cells, role in activation & produced by macrophages, TNF differentiation, neutrophil is able to induce fever recruitment Cytokines – Vasoactive amine - Histamine Very acute reaction Cell created it - chemical messenger - cause reaction and set of events Histamine comes from mast cells Acts on blood vessels Histamine causes dilation of arterioles & increase permeability Image from Wikipedia website Feb 2021 Prostaglandins Produced by mast cells, macrophages & endothelial cells Lipid compound Fat based cytokine Involved in vascular & systemic reactions of inflammation Causes vasodilation Fever Pain Leukotrienes Produced by leucocytes and mast cells by the action of lipoxygenase Act as chemotactic for neutrophils Usually accompanied by histamine & prostaglandins Releases lysosomal enzymes Vasoconstriction Anti inflammatory Chemokines Family of small proteins that act as primarily chemo-attractants for specific types of leukocytes. Enhancing chemotaxis Attract leukocytes Image from Wikipedia website Feb 2021  Definition Summary Causes of inflammation Chemical mediators Difference between in inflammation acute & chronic Names and functions of chemical mediators Patterns of acute Sign of inflammation Inflammation Events occurring in acute inflammation Vascular and cellular Where does this become relevant? Pathogenesis of Periodontal Disease Note down key words from today Inflammation friend or foe? Reading recommendations Ross & Wilson Anatomy and Physiology in Health and Illness, 13e Paperback – 6 Jun. 2018 Acute Inflammation - TeachMePhysiology