logging in or signing up UPUPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY doczay Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: Embed: Flash iPad Dynamic Copy Does not support media & animations Automatically changes to Flash or non-Flash embed WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 749 Category: Education License: All Rights Reserved Like it (0) Dislike it (0) Added: March 13, 2012 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... Premium member Presentation Transcript UPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY: UPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY DR.MUHAMMAD UZAIR KHAN WAZIRINTRODUCTION: INTRODUCTION Chronic Granulomatous Disease Mycobacterium leprae Affecting peripheral nerves and skin Discovered by Armauer Hansen in 1873 MYCOBACTERIUM LEPRAE: MYCOBACTERIUM LEPRAE Slow growing acid fast Rods No in-vitro cultivation First bacterium disease in humans Humans and Armadillos are only known natural hosts Pathophysiology: Pathophysiology Incubation period 6 months to 40 years or longer Average incubation period 2-5 years for tuberculoid leprosy, 8-12 years for lepromatous leprosy Affinity for macrophages and Schwann cellsCONT…: CONT… TLR2/1 recognise leprae lipoproteins Monocytes differentiate into macrophages & dendritic cell IL-12 & IL-2 production T lympocytes , expansion of a/b CD8 & natural killer cells INF لا- stimulates bactericidal mechanismsCONT…: CONT… Low Immunity Clonal anergy or active suppression of T-cells Defective or low production of IL-2 Defective Macrophage antigen recognition, presentation & KillingCONT…: CONT… NERVE DAMAGE Activation of TLR2 & TLR1 on schwaan cells Bind to G domain of the alpha-chain of laminin 2 in the basal lamina. CMI activation Apoptosis Activation of the ErbB2 receptor tyrosine kinaseCONT…: CONT… Expression of Cell Mediated Immunity Extant of Bacillary spread and multiplication Appearance of Immunological complications Nerve damage and its complicationsExtant of Bacillary spread & multiplication : Extant of Bacillary spread & multiplication Lepromatous Leprosy Spread to superficial & cool sites Eyes, Upper Respiratory mucosa, Testes, small muscles and bones of hand, feet & face, peripheral nerves & skin Tuberculoid Leprosy Bacilliary multiplication restricted No bacilli foundImmunological complications: Immunological complications TYPE I REACTION Upgrading and reversal reaction During 1 st 6 months Overproduction of Th1 –type cytokines Severe nerve damage Erythematous , red, raised, shinny, warm Immunological Complications…: Immunological Complications… ENL Inc. Th2 response Circulating immune complexes Immunoglobulins and complement in the lesion Increase T-cell response, inc. CD4 cells Inc. IL-2 receptors, IL-6 & TNF-aRecent Advances: Recent Advances Live bacilli suppresses DC and T-cell interaction TLR2/1 activated by Th-1 reaction, Th2 inhibits activation Helminthic co-infection and leprosy Inc. Th2 response & suppresses Th1 type immunity Dec. level of INF- لا , two fold inc. in IL-4 & IL-10 Facilitate leprae inf. Or progression to severe formCont…: Cont… Association with HLA (HLA-DRB1 & HLA-DQA) A fame shift mutation in NOD2 gene, having predisposition to Crohn’s diseaseTHANK YOU : THANK YOULeprosy (Hansen’s Disease) : Leprosy (Hansen’s Disease) You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
UPUPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY doczay Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: Embed: Flash iPad Dynamic Copy Does not support media & animations Automatically changes to Flash or non-Flash embed WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 749 Category: Education License: All Rights Reserved Like it (0) Dislike it (0) Added: March 13, 2012 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... Premium member Presentation Transcript UPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY: UPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY DR.MUHAMMAD UZAIR KHAN WAZIRINTRODUCTION: INTRODUCTION Chronic Granulomatous Disease Mycobacterium leprae Affecting peripheral nerves and skin Discovered by Armauer Hansen in 1873 MYCOBACTERIUM LEPRAE: MYCOBACTERIUM LEPRAE Slow growing acid fast Rods No in-vitro cultivation First bacterium disease in humans Humans and Armadillos are only known natural hosts Pathophysiology: Pathophysiology Incubation period 6 months to 40 years or longer Average incubation period 2-5 years for tuberculoid leprosy, 8-12 years for lepromatous leprosy Affinity for macrophages and Schwann cellsCONT…: CONT… TLR2/1 recognise leprae lipoproteins Monocytes differentiate into macrophages & dendritic cell IL-12 & IL-2 production T lympocytes , expansion of a/b CD8 & natural killer cells INF لا- stimulates bactericidal mechanismsCONT…: CONT… Low Immunity Clonal anergy or active suppression of T-cells Defective or low production of IL-2 Defective Macrophage antigen recognition, presentation & KillingCONT…: CONT… NERVE DAMAGE Activation of TLR2 & TLR1 on schwaan cells Bind to G domain of the alpha-chain of laminin 2 in the basal lamina. CMI activation Apoptosis Activation of the ErbB2 receptor tyrosine kinaseCONT…: CONT… Expression of Cell Mediated Immunity Extant of Bacillary spread and multiplication Appearance of Immunological complications Nerve damage and its complicationsExtant of Bacillary spread & multiplication : Extant of Bacillary spread & multiplication Lepromatous Leprosy Spread to superficial & cool sites Eyes, Upper Respiratory mucosa, Testes, small muscles and bones of hand, feet & face, peripheral nerves & skin Tuberculoid Leprosy Bacilliary multiplication restricted No bacilli foundImmunological complications: Immunological complications TYPE I REACTION Upgrading and reversal reaction During 1 st 6 months Overproduction of Th1 –type cytokines Severe nerve damage Erythematous , red, raised, shinny, warm Immunological Complications…: Immunological Complications… ENL Inc. Th2 response Circulating immune complexes Immunoglobulins and complement in the lesion Increase T-cell response, inc. CD4 cells Inc. IL-2 receptors, IL-6 & TNF-aRecent Advances: Recent Advances Live bacilli suppresses DC and T-cell interaction TLR2/1 activated by Th-1 reaction, Th2 inhibits activation Helminthic co-infection and leprosy Inc. Th2 response & suppresses Th1 type immunity Dec. level of INF- لا , two fold inc. in IL-4 & IL-10 Facilitate leprae inf. Or progression to severe formCont…: Cont… Association with HLA (HLA-DRB1 & HLA-DQA) A fame shift mutation in NOD2 gene, having predisposition to Crohn’s diseaseTHANK YOU : THANK YOULeprosy (Hansen’s Disease) : Leprosy (Hansen’s Disease)