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General Pathology

General Pathology. Basic Principles of Cellular and Organ Pathology Inflammation - IV. http://www1.lf1.cuni.cz/~jdusk/. Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague. Inflammation. Definition: complex reaction of organism to damage

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General Pathology

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  1. General Pathology Basic Principles of Cellular and Organ Pathology Inflammation - IV http://www1.lf1.cuni.cz/~jdusk/ Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague Inst. Pathol, 1st Med. Faculty, Charles Univ., Prague

  2. Inflammation Definition: complex reaction of organism to damage (aim: homeostasis maintenance)

  3. nonliving physical chemical Inflammation - Causes • living viral bacterial mycotic parasitic AUTOIMMUNE

  4. Nonspecific antibodies imunocomplexes on dendritic cells long lasting antigen presentation Inflammation– immunity

  5. antigen specific humoral B– lymphocytes cellular T– lymphocytes INTERACTION B-lympho–Th – affinity maturation – plasmocyte Mechanisms of ImmuneResponse

  6. lack of self-tolerance Autoimmunity

  7. constant activity in organogenesis regeneration metalaxia Autoimmunity

  8. Def.: loss of self-tolerance resulting into damage of organ /tissue Autoimmune Diseases

  9. Mechanisms Preventing Antiself Reactivity: • clonal deletion (thymus) • clonal anergy (thymus) • peripheral clonal supression by Tsupressor cells ( B,T helpers)

  10. DISEASE SLE RA Sjögren dis. Syst. sclerodermia Dermato–polymyositis Prim. vasc. syndromes ANTIBODY ANA, ENA collag. II, Fc –Ig (rheum. factor) ANA,ENA ENA (Scl–70) ENA (Jo–1) ANCA Inflammation – autoimmuneSystemic autoimmune diseases

  11. Sjögren´s syndrome Def.: a group of autoimmune conditions characterized by T-lymphocyte mediated sialo- & dacryoadenitis ---------- women predilection sicca (dry) syndrome

  12. Sjögren´s syndrome Classification: • primary: keratoconjunctivitis sicca, no co-existing systemic a-i diseases • secondary: accompanying rheumatoid arthritis, SLE, dermatomyositis….

  13. T.E.Daniels, Th.B. Aufdemorte, J.S.Greenspan:Histopathology of Sjögren´s syndrome. s. 41-52, in: N. Talal, H.M. Moutsopoulos, S.S.Kassan:Sjögren´s syndrome. Clinical and immunological aspects. Springer Vrlg, Berlin, Heidelberg, New York, London, Paris, Tokyo 1987, 299ss.

  14. Focus Score • Morphometric representation of focally accented chronic sialoadenitis • focus – agregate of 50 and more lymphocytes(defined 1968)

  15. Lichen planus fibrinogen Ab in BM Mucous Membrane Pemphigoid IgG, C3 along BM Pemphigus vulgaris IgG Erythema multiforme IgM,C3 deep dermis - perivascular J.P.Sapp et al. Contemporary maxillofacial pathology. 2nd ed. Mosby 2004

  16. ANTIBODY intercel. epith. matrix basal membrane of epidermis DISEASE pemphigus pemphigoid Inflammation – autoimmuneOrgan autoimmune diseases – skin

  17. ANTIBODY against mitochondrie membr. hct., cytosol gliadin DISEASE prim. bill. cirrhosis CAH gluten enteropathy Inflammation – autoimmuneOrgan autoimmune diseases – GIT

  18. man 27 yrs B 2138/06 • 4 pieces from D3 announced • 3 pieces diam. 1-2mm found • clin. dg. susp. celiakia, diff. dg. lambliasis

  19. Histopathology Report • mild shortening & widening of villi • intraepit. lymphocytes > 40/100 enterocytes • lamblie not found Conclusion: histopathology changes supporting clinical dg. suggested - celiac sprue - type 3a of Marsh´ classification

  20. Marks, DJB, Harbord, MWN, Mac Allister R. et al.: Impotent immune System: An Underlying Problem in Crohn´s Disease. Lancet 2006, 367, 668-78 • in patients with Crohn´s an impaired acute inflammatory response – 79% reduction in the number of neutrophils and interleukin 8 • in ulcerative colitis initiation of inflammation normal, resolution delayed

  21. ANTIBODY TGB, microsomes pancreas  cells insulin ins. receptors adrenal microsomes TSH rec. DISEASE GB, HT DM I I–res. DM I–res. DM Adison dis. GB Inflammation – autoimmuneOrgan autoimmune diseases – endocrine

  22. ANTIBODY acetylcholin rec. basic myelin protein DISEASE myasthenia gravis disseminated sclerosis Inflammation – autoimmuneOrgan autoimmune diseases – CNS

  23. Hypersensitivity • anaphylactic astma IgE • cytotoxic erythroblastosis IgG, IgM • immune complexes SLE, GN Ag+AB+C • cell mediated (delayed) tbc, contact dermatitis – T-cell mediated cytotoxicity

  24. Defenses Against Infection – 1. • Surface • barriers: skin, conjunctiva, mucous membranes • mechanical removal: shedding, tears, mucus, ciliary action, coughing, salivation, swallowing, urination, defecation • normal bacterial flora • chemical inhibitors: gastric acid, lactic acid, fatty acids,bile salts.. • antimicrobial substances: lysozym, secretory IgA

  25. Defenses Against Infection – 2. • Nonspecific resistance factors • fever, interferon, complement, lysozyme, C-reactive protein, lactoferrin, α1- antitrypsin • Inflammation- soluble factors • clotting system –Hageman fc. (XII) • complement system: chemotactic fc, anaphylatoxins • kinin system: bradykinin • Inflammation- phagocytes • circulating: neutrophils, eosinophils, monocytes, macrophages • fixed: alveoli, spleen, liver, bone marow

  26. Defenses Against Infection – 3. • Immune response • humoral: B-cells, plasma cells, immunoglobulins • cell-mediated: T-cells, lymphokins

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