1. Integrated Course Microbiology & Pathology Pathology of Tuberculosis Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

2. Inflammation - Classification: Type of granulation tissue: v nonspecific v „specific“ GRANULOMATOUS

3. v TUBERCULOSIS v sarcoidosis v syphilis v lepra v inf. scleroma (rhinoscleroma) v lymphogranuloma venereum (inguinale) v (brucelosis, listeriosis, tularemia,…..) Granulomatous Inflammatory Diseases

4. TUBERCULOSIS Mycobacterium tuberculosis (Koch 1882) Mycobacterium bovis acidoresistance M. avium,intracellulare, Kansasii atypical mycobacterioses

5. THE TUBERCULOSIS EPIDEMIC AND RESPONSE u 95% of TB deaths are in the developing world. u 8.8 million fell ill with TB in 2010, including 1.1 million people with HIV. u 1.4 million died from TB in 2010, including 350,000 people with HIV, equal to 3,800 deaths a day. u In 2009 9.7 million orphan children as a result of TB deaths u TB is among the three greatest killers among women aged 15-44 u Since 1995, 46 million people successfully treated and 6.8 million lives saved - Stop TB Strategy.

6. TUBERCULOSIS u portae invasionis – respiratory tract – gastrointestinal tract – skin u types of disease (clinicoepidemiol. view) v open tbc v closed

7. infected macrophage activated macrophage intracellular parasites mature Th clone creation cytokins & bactericid subst. secretion interferon γ interferon receptor Macrophage activation blockage Trehalose 6,6´-Dimycolate TDM is one of the many lipids in the Mycobact wall. It is the most toxic, most granulomagenic and most abundant extractable lipid from the Mycobacterium surface.

8. Genetically determined susceptibility to mycobacterial infection. u mutations in the IFNgammaR1 or R2 genes, resulting in defective expression or function of the IFNgamma receptor u cell surface expression IL12Rbeta1gene, resulting in the inability to respond to IL12 u inability to produce IL12, due to deletion within the gene coding for the inducible chain of IL12 (IL12-p40) Patel SY, Doffinger R, Barcenas-Morales G, Kumararatne DS.: Genetically determined susceptibility to mycobacterial infection. J Clin Pathol. 2008 Sep;61(9):1006-12.

9. Granuloma - composition 1. MACROPHAGES 2. lymphocytes 3. fibrous deposits of collagen 4. central necrosis

10. TUBERCULOSIS Type of infection v childhood (primary, preimmune) v adult (postprimary, immune)

11. TUBERCULOSIS Morphological features u primary infect (Ghon focus) & primary complex u caseification u isolated organ metastasis u tubercle, exsudate, cavity u early and late generalisation – milliary spread

12. TUBERCULOSIS Type of infection v childhood (primary, preimmune) v adult (postprimary, immune)

13. TUBERCULOSIS Terms –Forms– Locations : u phtisis gallopans u scrofulosis u meningitis basillaris u lupus vulgaris u mallum Potti, cold absces

14. Diagn Cytopathol. 2010 Dec 30. [Epub ahead of print] Gall bladder tuberculosis masquerading as carcinoma: Dilemma resolved by aspiration cytology. Verma R, Vij M, Pal L. Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India.

15. Picque JB, Blot M, Binois R, et al.: Recurrent atypical mycobacterial infections in the adult: think of autoantibodies against interferon- gamma ! [Article in French] Rev Med Interne. 2012 Feb;33(2):103-6. Département d'infectiologie Dijon, France. INTRODUCTION: Disseminated non-tuberculosis mycobacterial infections mainly reported in AIDS patients. Cases related to the presence of anti-interferon-γ autoantibodies are rare. CASE REPORT: A non HIV-infected 45-year-old Thai woman, history of Graves' disease presented with recurrent disseminated and severe non-tuberculous mycobacterial infections production of anti-interferon-γ autoantibody. evidenced by the identification of specific antibodies. CONCLUSION: Anti-interferon-γ autoantibody production is a rare cause of non tuberculous mycobacterial infection. It should be suspected in non HIV-infected patients A negative IGRA (including with the positive control) is a reliable diagnostic tool and should be completed with the identification of specific autoantibodies.