IT_Leprosy.sindhu final.pptx integrated teaching

Leprosy pathogensis

1. LEPROSY INTEGRATED TEACHING DR.SINDHU JADHAV Gerhard Armauer Hansen

2. INTRODUCTION Leprosy- Hansen disease- chronic granulomatous infection caused by M. leprae Leprosy is a chronic infectious disease whose clinical spectrum is dependent upon the immunological status of the patient. Inhalation of bacilli, excreted from nasal passages of a multibacillary patient or implanted from organisms in soil

3. Earliest lesion - intra-epidermally as lymphocytic infiltration. Histopathologic aspects and the immune state of the patient is the basis of leprosy classification Majority of bacilli are present mainly in macrophages Bacilli also seen inside monocytes, Schwann cells, polymorphs and columnar and goblet cells of pseudostratified epithelium of upper respiratory and nasal glands

4. Pathogenesis of Leprosy Pathogenesis involves a chronic granulomatous infection 1) Entry of pathogen 2) Host Response and Immune Interaction The bacteria have a unique ability to evade the immune system by replicating within macrophages. 3) Nerve Damage 4) Tissue Damage and Deformities 5 ) Spread and Chronicity .

5. .

6. Mycobacteria Alveolar macrophage Mannose-capped glycolipid Macrophage mannose receptor (Mannose-Binding Lectin & Type 3 Complement Receptor ) Endosomal manipulation Maturation arrest Lack of acid pH Ineffective phagolysosome formation ? N-RAMP1 polymorphism Bactereremia with seeding of multiple sites Unchecked bacillary proliferation PATHOGENESIS OF LEPROSY host protein CORONIN recruited to membrane of phagosome. Coronin activates phosphatase calcineurin, leading to inhibition of phagosome-lysosome fusion ENTRY INTO MACROPHAGES REPLICATION IN MACROPHAGES

7. T-cell Th1 iNOS Alveolar macrophage IL-12 Dendritic Class II MHC ML antigen T-cell receptor TLR2&TLR9 γ -IFN Activated macrophage Nitric oxide & Free radicals Bactericidal activity (immunity) Lepromin test positivity (hypersensitivity ) Monocyte recruitment TNF Sensitized T-cell Epithelioid Granuloma (hypersensitivity) PATHOGENESIS OF LEPROSY Mycobacterial lipoarabinomannan binds TLR2, & unmethylated CpG nucleotides bind TLR9- & stimulate immunity INNATE IMMUNITY TH1 RESPONSE TH1-MEDIATED MACROPHAGE ACTIVATION & KILLING OF BACTERIA GRANULOMATOUS INFLAMMATION & TISSUE DAMAGE

8. Disease Spectrum (Immunological Basis) The clinical manifestations of leprosy depend on the host’s immune response and vary across a spectrum: Differences -Tuberculoid & Lepromatous leprosy Tuberculoid leprosy high cellular immune response -T cells and macrophage activation - few bacilli in tissues Lepromatous leprosy cellular immune response to M. leprae antigens- absent no macrophage activation abundant bacilli in tissues.

9. RIDLEY - JOPLING CLASSIFICATION Combination of clinical, microbiologic, histopathologic, and immunologic indices INDETERMINATE STABLE STABLE UNSTABLE UNSTABLE UNSTABLE Type I Reactions ENL Cell mediated immunity Bacterial load

10. LEPROSY SPECTRUM TT and LL - stable Patients presenting at BT point - often downgrade toward BL Central point of spectrum (BB) - most unstable, with patients downgrading to LL Indeterminate leprosy- too early to categorize- self heal or go into TT, BL or LL

11. TUBERCULOID LEPROSY Lesions- few, erythematous, hypopigmented papules or plaques with sharply defined edges.

12. TUBERCULOID LEPROSY Extensive infiltration of dermis and subcutaneous fat by granulomas Infiltration by giant cells and lymphocytes

13. LEPROMATOUS LEPROSY Initially has cutaneous and mucosal lesions, with clinically manifested neural changes Lesions usually numerous and symmetrically arranged Three clinical types: Macular Infiltrative-nodular Diffuse

14. LEPROMATOUS LEPROSY Grenz zone Wade fite stain

15. LEPROMATOUS LEPROSY Infiltration of dermis by large no. of histiocytes

16. Lepromin skin test/ Mitsuda test Consists of the intradermal injection of a preparation of M. leprae derived from autoclaved infected human tissue. A positive reaction- formation of a nodule measuring 5 mm in diameter or more after 2 to 4 weeks. Histologic examination: the nodule shows an epithelioid cell granuloma. The reaction is positive only in the high-resistance (TT and BT tuberculoid) forms of the disease. In indeterminate leprosy, it may be positive or negative