Acute Chronic Inflammation - Jonathan Salisbury PDF

Histopathology of Inflammation Dr Jon Salisbury Department of Histopathology King’s College Hospital Immunology Roadmap Innate immunity Adaptive immunity Microbes B lymphocytes Antibodies Epithelial...

Histopathology of Inflammation Dr Jon Salisbury Department of Histopathology King’s College Hospital Immunology Roadmap Innate immunity Adaptive immunity Microbes B lymphocytes Antibodies Epithelial barriers T lymphocytes Phagocytes C3a C3b Effector T cells NK cells Complement Immunology Roadmap- Histopathology of inflammation Innate immunity Adaptive immunity Acute inflammation Chronic inflammation Microbes B lymphocytes Antibodies Epithelial barriers T lymphocytes Phagocytes C3a C3b Effector T cells NK cells Complement Topics Inflammation - definitions Acute Inflammation Movement of cells into an acute inflammatory lesion Chronic Inflammation Inflammation – definitions Inflammation The reaction of vascularised living tissue to local injury. In higher animals the reaction of the blood vessels to local injury , leads to the accumulation of fluid and cells that characterize inflammation. Tissues that are not vascularised such as the cornea do not become inflamed according to the classical definitions  Repair The replacement of injured tissue either by regeneration if the damaged parenchyma can divide and be replaced..or by fibroblastic or glial “scar” tissue Inflammation and repair Inflammation and repair can meet a challenge and restore tissue to health Inflammation and repair can contribute in different ways to many tissue diseases such as: Fibrous Rheumatoid arthritis –Renal bowel inflammation adhesions persistent following surgery autoimmune inflammation Acute Inflammation Cornelius Celsus, Roman, 1st Century AD The four cardinal signs of inflammation: RUBOR - redness TUMOUR - swelling CALOR - heat DOLOR - pain Acute inflammation - mediated by the innate immune system Relatively rapid onset, short duration, stereotyped response, rapid resolution. Vascular changes Transient vasoconstriction of arterioles Vasodilatation and increased blood flow Slowing of the circulation because of increased permeability of the microvasculature.’ Stasis’ Exudation of fluid and plasma proteins (oedema) Acute serous inflammation Sometimes accumulation of fluid is the dominant feature of inflammation, as observed in a friction blister or a burn.  Acute inflammation may be accompanied by: Exudate An inflammatory extravascular fluid that has a high protein concentration, much cellular debris and a S.G. above 1020 (In comparison to transudates that are ultrafiltrates of low protein content (mostly albumin) and a S.G. less than 1012) Pus A purulent exudate rich in leucocytes (mostly neutrophils) and parenchymal cell debris Movement of cells into an acute inflammatory lesion  Blood cells normally move rapidly through the centre of blood vessels v v Release of P-selectin to endothelial surface on Store Weibel-Palade INFLAMMATION! stimulation with P-selectin Bodies histamine complement C5a or LPS Expression of P-selectin and also E-selectin on the endothelium causes neutrophils to slow down by interacting with carbohydrate receptors and roll along the endothelium. Neutrophil rolling Margination = increased adhesion v of inflammatory cells v to endothelium and rolling along endothelium Release of chemokine such as IL-8 (CXCL8) that attracts neutrophils v v along a concentration gradient in response to stimuli such as LPS  Chemotaxis The unidirectional migration of cells towards a chemokine The main inducers of chemotactic agents for neutrophils are: 1. Bacterial products 2. Components of the complement system, particularly c5a 3. Products of the lipoxygenase pathway of arachidonic acid metabolism, particularly leukotriene B4.  Interaction between integrin molecules on leukocytes and endothelial adhesion molecules such as ICAM-1 makes a firmer connection to permit diapedesis (movement across endothelium) and extravasation. v v Extravasation = movement of cells into tissues following the chemokine gradient. Acute suppurative inflammation Acute fibrinous inflammation Acute membranous inflammation What follows acute inflammation? Resolution Acute Inflammation Abscess Injury formation Chronic Inflammation Healing/ scarring/ Persistent infection regeneration Persistent toxin Autoimmune challenge Chronic Inflammation Chronic inflammation Relatively long duration Associated with the presence of lymphocytes and macrophages Proliferation of blood vessels and connective tissue Not uniform as many factors modify the course and histological appearance Chronic inflammation 1. May follow acute inflammation 2. May begin as a low grade smouldering response persistent infections by intracellular organisms prolonged exposure to non-degradable substances autoimmune diseases  Histology of chronic inflammation 1. Infiltration by mononuclear cells Macrophages Lymphocytes Plasma cells 2. Proliferation of fibroblasts and small blood vessels Increased connective tissue and fibrosis Chronic granulomatous inflammation Blood derived lymphocytes and Non-caseating (non-infectious) macrophages epithelioid granuloma Fibroblasts producing collagen Necrosis Macrophage Early granuloma: necrosis attracting Macrophages with a cuff chemokines of lymphocytes Caseating (infectious) epithelioid granuloma  Foreign body granulomas Giant cells can phagocytose large foreign Bi-refringence in polarised light material allows visualisation of foreign material – silicon in this example Pulmonary tuberculosis – granulomatous inflammation