Adobe Systems Pathophysiology of chronic inflammation, ethiopathogenesis, consequences, systemic inflammation, SIRS, MODS Julie Dobrovolná Adobe Systems Immune system •Immune system = cells, tissues and molecules that mediate resistance to infections •Immunology = study of the structure and function of the immune system Immunity = host resistance to pathogens and their toxic effects •Immune response = collective and coordinated response to the introduction of foreign substances into an individual mediated by cells and immune molecules system ̶ Adobe Systems The role of the immune system ̶Defense against microbes ̶Defense against tumor cell growth kills tumor cell growth ̶Homeostasis of destruction of abnormal or dead cells (e.g. dead red or white blood cells, antigen-antibody complex) Adobe Systems The components of the immune system Adobe Systems The type of immune response ̶Innate (non-adaptive): the first-line immune response relies on mechanisms that existed before infection ̶Acquired (adaptive) immunity: The second line of response (if innate immunity fails) relies on mechanisms involving cellular memory of key T- and B-lymphocytes Adobe Systems Timeline Adobe Systems Adobe Systems Innate immunity ̶Based on genetic background ̶Relies on existing system components ̶Rapid response: within minutes of infection ̶Not specific: the same molecules / cells respond to many pathogens ̶No memory: the same response after repeated exposure ̶Does not lead to clonal expansion Adobe Systems Innate immunity mechanisms ̶Mechanical barriers / excretion on the skin surface, acidic pH in the stomach, cilia ̶Humoral mechanisms ̶Lysozymes, basic proteins, complement, interferons ̶Mechanisms of cell defense by natural killers (NK cells) neutrophils, macrophages, mast cells, basophils, eosinophils Adobe Systems Adaptive immunity ̶Based on resistance acquired during life ̶Relies on the genetic background of the individual and cell growth ̶The reaction is slower, in a number of days ̶It is specific ̶Each cell responds to one epitope on the antigen ̶It has anamnestic memory ̶Repeated exposure leads to a faster and stronger reaction ̶It leads to clonal expansion Adobe Systems Adaptive immunity mechanisms •Cell-mediated immune response (CMIR) •T-lymphocytes •Elimination of intracellular microbes that survive inside phagocytes or other infected cells • •Humoral immune response (HIR) •B-lymphocytes •antibody-mediated •Elimination of intracellular microbes or their toxins Adobe Systems Adaptive immunity: mechanisms Adobe Systems Zápatí prezentace 13 Inflammation Inflammation Inflammation is a protective response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult The reaction of vascularized living tissue to local injury. How inflammation accomplishes its protective mission? How to accomplishes protective mission? Inflammation serves to destroy, dilute or isolate the injurious agent (microbes, toxins) and eliminate the necrotic cells and tissues. Inflammation is part of a broader protective response (innate immunity ) It starts a series of events which leads as far as possible to the healing and reconstitution of the damaged tissue. Inflammation During repair, the injured tissue is replaced by : •Regeneration of native parenchyma cells •Filling of the defect by fibroblastic tissue or both Inflammation and repair are protective response u Can Inflammation cause considerable harm to the body? They may induce harm e.g. anaphylactic reaction rheumatoid arthritis atherosclerosis pericarditis How? ¨The components of the inflammatory reaction that destroy and eliminate microbes and dead tissues are capable of also injuring normal tissues. ¡This may accompany entirely normal, beneficial inflammatory reactions, (e.g., when the infection is severe), prolonged (e.g., when the eliciting agent resists eradication) inappropriate (e.g., when it is directed against self-antigens in autoimmune diseases) against usually harmless environmental antigens (allergic disorders) Then what happens? Inflammation is terminated when the offending agent is eliminated and the secreted mediators are broken down or dissipated. There are active anti-inflammatory mechanisms that serve to control the response and prevent it from causing excessive damage to the host. What are the cells and molecules that play important roles in inflammation? blood leukocytes plasma proteins cells of vascular walls cells of the surrounding connective tissue extracellular matrix (ECM) of the surrounding connective tissue The connective tissue cells The circulating cells: The extracellular matrix D:\SCContent\9781416029731\graphics\fullsize\S9781416029731-002-f001.jpg Cells and molecules that play important roles in inflammation Tissues and cells involved in inflammatory response : The fluid and proteins of plasma, circulating cells, blood vessels and connective tissue •The circulating cells: neutrophils, monocytes, eosinophils, lymphocytes, basophils, and platelets. • • The connective tissue cells are the mast cells, the connective tissue fibroblasts, resident macrophages and lymphocytes. • •The extracellular matrix, consists of the structural fibrous proteins (collagen, elastin), adhesive glycoproteins (fibronectin, laminin, nonfibrillar collagen, tenascin, and others), and proteoglycans What are types of inflammation? What is the difference between these types of inflammation? Acute inflammation ¨rapid in onset (seconds or minutes) ¨relatively short duration, lasting for minutes, several hours, or a few days ¨ its main characteristics: ¡ the exudation of fluid and plasma proteins (edema) ¡ the emigration of leukocytes, predominantly neutrophils. ¨ ¨ ¨ ¨is of longer duration ¨associated histologically with the presence of lymphocytes and macrophages, the proliferation of blood vessels, fibrosis, and tissue necrosis. ¨Less uniform. Chronic inflammation What is the source of chemical mediators in inflammation? What is the action of chemical mediators in inflammation? Some of mediators act on small blood vessels Promote the efflux of plasma Recruitment of circulating leukocytes to the site where the offending agent is located What are the cardinal signs of inflammation? Acute Inflammation Local clinical signs of acute inflammation: ØHeat Ø ØRedness ØSwelling ØPain ØLoss of function SKIN166 Redness The cardinal signs of inflammation are rubor (redness), calor (heat), tumor (swelling), dolor (pain), and loss of function. Seen here is skin with erythema, compared to the more normal skin at the far right. SKIN167 Swelling The arm at the bottom is swollen (edematous) and reddened (erythematous) compared to the arm at the top. Click to determine which areas are painful to touch. SKIN072 Swelling Here is simple edema, or fluid collection within tissues. This is "pitting" edema because, on physical examination, you can press your finger into the skin and soft tissue and leave a depression. What are the steps of the inflammatory response which can be remembered as the five Rs? Steps of the inflammatory response (1) Recognition of the injurious agent (2) Recruitment of leukocytes (3) Removal of the agent (4) Regulation (control) of the response (5) Resolution Learning Objectives: 1. Define inflammation, its causes and clinical appearance. 2. 2.Describe the sequence of vascular changes in acute inflammation (vasodilation, increased permeability) and their purpose. 3. 3. Know the mechanisms of increased vascular permeability. 4. 4. Define the terms edema, transudate, and exudate. ¨ What are the two major components of acute inflammation? Components of acute inflammation VASCULAR CHANGES CELLULAR EVENTS ¨Vasodilation: alterations in vessel caliber resulting in increased blood flow ¨Increased vascular permeability: permit plasma proteins to leave the circulation ¨ ¡ ¨Emigration of the leukocytes from the microcirculation and accumulation in the focus of injury ¨Principal leukocytes in acute inflammation are neutrophils (polymorphonuclear leukocytes). ¨ Adobe Systems Zápatí prezentace 39 Chronic inflammation ̶Is a pathogenic process of chronic duration (weeks, months, years) ̶Where attempts at healing, inflammation and persistent tissue damage occur in different proportions Adobe Systems Zápatí prezentace 40 Causes of chronic inflammation ̶Persistent infection ̶Toxic agents (pollutants, etc) ̶Immune-mediated inflammatory diseases Adobe Systems Zápatí prezentace 41 Primary chronic inflammation ̶Is the cause of tissue damage in some of the most common and disabling human diseases ̶ ̶Rheumatoid arthritis ̶Atherosclerosis ̶Primary pulmonary fibrosis ̶Tuberculosis ̶ ̶Also, the chronic inflammation has been implicated in progression of cancerous lesions Adobe Systems Zápatí prezentace 42 Mechanisms of chronic inflammation Adobe Systems Zápatí prezentace 43 Morphological features of chronic inflammation ̶ Adobe Systems Zápatí prezentace 44 The role of macrophages in chronic inflammation Adobe Systems Zápatí prezentace 45 The role of macrophages in chronic inflammation Obsah obrázku mapa Popis byl vytvořen automaticky Adobe Systems Zápatí prezentace 46 The role of macrophages in chronic inflammation Adobe Systems Zápatí prezentace 47 The role of macrophages in chronic inflammation Adobe Systems Zápatí prezentace 48 The role of neutrophils in chronic inflammation Adobe Systems Zápatí prezentace 49 The role of neutrophils in chronic inflammation Adobe Systems Zápatí prezentace 50 The role of neutrophils in chronic inflammation Adobe Systems Zápatí prezentace 51 Age-dependent consequences Adobe Systems SIRS – systemic inflammatory response syndrome •Generalized acute inflammatory reaction that spreads throughout the body •Intense inflammatory response to primary local, multiple or otherwise complex damage •In SIRS, subsequent inflammation is not limited to the area where the inflammation occurred, but spreads throughout the body •Even common inflammation spreads throughout the body - the difference from SIRS is that in SIRS, the mechanisms of inflammation control stop working Adobe Systems Adobe Systems Zápatí prezentace 54 Pathogenesis of Covid-19 disease ̶Coronaviruses belong to the Coronaviridae family in the Nidovirales order ̶Corona represents crown-like spikes on the outer surface of the virus; thus, it was named as a coronavirus ̶Coronaviruses are enveloped viruses, minute in size (65–125 nm in diameter) and contain a single-stranded RNA as a nucleic material, size ranging from 26 to 32kbs in length Adobe Systems Zápatí prezentace 55 Covid-19 ̶The virus that causes COVID-19 is known as SARS-CoV-2 It appears to have first emerged in Wuhan, China, in late 2019. ̶The outbreak has since spread across China to other countries around the world. By the end of January, the new coronavirus had been declared a public health emergency of international concern by the WHO. ̶The most commonly reported symptoms include a fever, dry cough and tiredness, and in mild cases people may get just a runny nose or a sore throat. ̶ In the most severe cases, people with the virus can develop difficulty breathing, and may ultimately experience organ failure. Some cases are fatal. ̶ ̶ Adobe Systems Zápatí prezentace 56 Human coronaviruses ̶The most likely ecological reservoirs for coronaviruses are bats, but it is believed that the virus jumped the species barrier to humans from another intermediate animal host. ̶This intermediate animal host could be a domestic food animal, a wild animal, or a domesticated wild animal which has not yet been identified. ̶ Comet Supercomputer, TSCC Made Available for COVID-19 Research ... Adobe Systems Zápatí prezentace 57 Covid-19 timeline Adobe Systems Zápatí prezentace 58 Pathogenesis of Covid-19 disease Adobe Systems Zápatí prezentace 59 Pathogenesis of Covid-19 disease Adobe Systems Zápatí prezentace 60 Pathogenesis of Covid-19 disease ̶Coronavirus is one of the major pathogens that primarily targets the human respiratory system. Previous outbreaks of coronaviruses (CoVs) include the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome (MERS)-CoV which have been previously characterized as agents that are a great public health threat. In late December 2019, a cluster of patients was admitted to hospitals with an initial diagnosis of pneumonia of an unknown etiology. Adobe Systems Zápatí prezentace 61 Pathogenesis of Covid-19 disease Adobe Systems Zápatí prezentace 62 SIRS and Covid-19 Adobe Systems Zápatí prezentace 63 Pathogenesis of Covid-19 disease – key steps Adobe Systems SIRS •Generalized deregulated destructive process •Often associated with the devastation of distant organs •In hypersensitivity individuals, SIRS may occur even with very small amounts of antigen •Classification: •1) septic SIRS - associated with infection •2) unseptic SIRS - after severe trauma, hypoxemia, burns, poisoning, incompatible transfusion Adobe Systems Septic SIRS ̶Disseminated microbial infection ̶50% - gram-positive bacteria, 30% - gram-negative bacteria, 5% - polymicrobial infections, 5% yeasts and fungi and 1% anaerobes ̶1/3 of those affected die ̶ Primary SIRS Secondary SIRS Adobe Systems MODS Adobe Systems Zápatí prezentace 67 SIRS, MODS and Covid-19 Adobe Systems Adobe Systems Zápatí prezentace 69 Thank you for you attention Obsah obrázku text Popis byl vytvořen automaticky