Lecture 3.1 - Chronic Inflammation PDF

Introduction: ◦Unlike acute inflammation, chronic inflammation is long-lived ‣ >3 weeks ‣ May persist for many weeks, months and even years ◦Involves a much greater store of cells than acute inflammation ‣ This contributes to its severity ‣ Also ma...

Introduction: ◦Unlike acute inflammation, chronic inflammation is long-lived ‣ >3 weeks ‣ May persist for many weeks, months and even years ◦Involves a much greater store of cells than acute inflammation ‣ This contributes to its severity ‣ Also makes resolution more difficult Chronic inflammation: ◦“Chronic response to injury with associated fibrosis” ‣ Lots of chronic inflammatory cells present ‣ Granulation tissue - presence of fibrous tissue with small blood vessels From cell injury to tissue repair: How does chronic inflammation arise?: ◦May ‘take over’ from acute inflammation ‣ If damage is too severe to be resolved within a few days ◦May arise de novo - presence of inflammation without the presence of acute inflammation beforehand ‣ Some autoimmune conditions (e.g. rheumatoid arthritis) ‣ Some chronic infections (e.g. viral hepatitis) ◦May develop alongside acute inflammation ‣ In severe persistent or repeated irritation Chronic inflammation - what does it look like?: ◦Characterised by the microscopic appearance which are much more variable than acute inflammation ◦Most important characteristic is the type of cell present - many cells present (macrophages and lymphocytes) ‣ Which cell type is the most prevalent in acute inflammation? ‣ Not the case for chronic inflammation  Macrophages: ◦Derived from blood monocytes (circulating cell) ◦They are tissue resident ‣ Sense infection within tissues ◦Important in chronic inflammation ◦Functions: ‣ Phagocytosis and destruction of debris and bacteria ‣ Processing and presentation of antigen to immune system ‣ Synthesis of not only cytokines, but also complement components, blood clotting factors and proteases ‣ Control of other cells by cytokine release ‣ Resolution of inflammation Clearance of dead neutrophils Release of anti-inflammatory cytokines such as IL10 (interleukin 10) Lymphocytes: ◦Sometimes called ‘chronic inflammatory cells’ ‣ But are a normal component of many tissues ◦Functions: ‣ Complex, mainly immunological ‣ T lymphocytes involved in control and some cytotoxic functions ‣ B lymphocytes differentiate to produce antibodies Other cells involved in the chronic inflammatory response: ◦Plasma cells: ‣ Differentiated antibody-producing B lymphocytes. Usually implies considerable chronicity ◦Eosinophils: ‣ Allergic reactions, parasite infestations, some tumours ◦Fibroblasts/myofibroblasts: ‣ Recruited by macrophages; make collagen ‣ Fibroblasts is the main cell that forms collagen. To increase cell contractability, fibroblasts differentiate into myofibroblasts to support this change. ‘Giant cells’: ◦Multinucleate cells made by fusion of macrophages ◦Frustrated phagocytosis - happens when phagocytosis is disrupted, possibly due to a foreign body ◦Several types recognised:  ‣ Langhans (tuberculosis) - if there is an increased presence of these cells, tuberculosis is indicated ‣ Foreign body type - nuclei are arranged randomly due to presence of foreign material ‣ Touton (fat necrosis) - nuclei are arranged in centre, and linked to the presence of fat necrosis therefore_ae_ Cell types in chronic inflammation: ◦Make-up of most chronic inflammatory reactions is non-specific, BUT proportions of each cell type may vary in different conditions ◦For example: ‣ Rheumatoid arthritis - mainly plasma cells and synovial fibroblasts ‣ Chronic gastritis - mainly lymphocytes ‣ Leishmaniasis (a protozoal infection) - mainly macrophages and eosinophils ‣ Giant cell type - may be a help with diagnosis (e.g. TB) Effects of chronic inflammation: ◦Fibrosis - replacing normal tissue with fibrous tissue: ‣ E.g. gall badder (chronic cholecystitis - chronic inflammation of the gallbladder), chronic peptic ulcers, cirrhosis of the liver ◦Impaired function: ‣ E.g. chronic inflammatory bowel disease (Ulcerative colitis or Crohn's disease) ‣ Rarely increased function e.g. mucus secretion, thyrotoxicosis ◦Atrophy: ‣ Gastric mucosa and adrenal glands (smaller and shrunken organs due to damage) ◦Stimulation of immune response: ‣ Macrophage - lymphocyte interactions FTIease fsehead Fibrosis: chronic cholecystitis: ◦Repeated obstruction by gall stones ◦Repeated acute inflammation leads to chronic inflammation ◦Fibrosis (scarring) of gall bladder wall Chronic Cholecystitis:  Inflammatory bowel disease: ◦Idiopathic inflammatory disease affecting large and small bowel ◦Patients present with diarrhoea, rectal bleeding and other symptoms todtEeeeeeer ◦Ulcerative colitis and Crohn’s disease Impaired function: Inflammatory bowel disease: ◦Ulcerative colitis is superficial - only affects the mucosa ‣ Diarrhoea, bleeding ‣ Ulcers can be caused by infection with H.pylori (bacteria that lives in the intestine) ◦Crohn’s disease is transmural - affects the whole wall ‣ Strictures (narrowing of intestine), fistulae (fistula = abnormal connection between two epithelium-lined organs) Fibrosis and impaired function - Cirrhosis: ◦Chronic inflammation with fibrosis (disorganisation of architecture, attempted regeneration) leads to Cirrhosis ◦Common causes of cirrhosis: ‣ Alcohol ‣ Infection with HBV, HCV (hepatitis B and C) ‣ Immunological ‣ Fatty liver disease ‣ Drugs and toxins Increased function: thyrotoxicosis: Atrophy: gastric mucosa: ◦Chronic inflammation of the gastric mucosa can lead to loss of the gastric glandular cells and replacement by intestinal-type epithelium and fibrous tissue  Chronic inflammation and immune response: ◦Chronic inflammation and immune responses overlap ‣ Immune diseases cause pathology by chronic inflammation ‣ Chronic inflammatory processes can stimulate immune responses Autoimmune diseases Granulomatous inflammation: ◦Granulomatous inflammation = chronic inflammation with Granulomas ◦Granulomas arise due to: ‣ Persistent antigenic stimulation ‣ Hypersensitivity Main causes of Granulomatous inflammation: ◦Mildly irritant ‘foreign’ material ◦Infections: ‣ Mycobacteria - tuberculosis, leprosy ‣ Other infections e.g. some fungi ◦Unknown causes: ‣ Sarcoid ‣ Crohn’s disease Foreign material from breakdown of artificial joint:  Tuberculosis: ◦Caused by mycobacteria: ‣ Especially M.tuberculosis ‣ Difficult and slow to culture ◦Nature of organism ‣ Wall lipids (Mycosides) ◦Produces no toxins or lyric enzymes ◦Causes disease by persistence and induction of cell-mediated immunity assessed ‣ Biofilm production Granulomatous disease of unknown cause: ◦Sarcoidosis ‣ Variable clinical manifestations: Young adult women Non-caseating Granulomas (do not cause necrosis) ◦Crohn’s disease ‣ Regional enteritis - patchy full-thickness inflammation throughout bowel ◦Granulomatosis with polyangitis ‣ Causes Granulomatious inflammation in the vasculature