UPUPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY

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UPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY:

UPDATES IN THE PATHOPHYSIOLOGY OF LEPROSY DR.MUHAMMAD UZAIR KHAN WAZIR

INTRODUCTION:

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 cells

CONT…:

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 mechanisms

CONT…:

CONT… Low Immunity Clonal anergy or active suppression of T-cells Defective or low production of IL-2 Defective Macrophage antigen recognition, presentation & Killing

CONT…:

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 kinase

CONT…:

CONT… Expression of Cell Mediated Immunity Extant of Bacillary spread and multiplication Appearance of Immunological complications Nerve damage and its complications

Extant 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 found

Immunological 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-a

Recent 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 form

Cont…:

Cont… Association with HLA (HLA-DRB1 & HLA-DQA) A fame shift mutation in NOD2 gene, having predisposition to Crohn’s disease

THANK YOU :

THANK YOU

Leprosy (Hansen’s Disease) :

Leprosy (Hansen’s Disease)