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General Pathology

General Pathology. Basic Principles of Cellular and Organ Pathology Inflammation - IV. CD3. http://www1.lf1.cuni.cz/~jdusk/. Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague. decreased – immunodeficiency vascular - DM, ischemia - atherosclerosis primary – inborn

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General Pathology

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  1. General Pathology Basic Principles of Cellular and Organ Pathology Inflammation - IV CD3 http://www1.lf1.cuni.cz/~jdusk/ Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague

  2. decreased –immunodeficiency vascular - DM, ischemia - atherosclerosis primary – inborn NG disorders thymic hypoplasia T-lymphopenia Bruton´s agamaglobulinemia isolated IgA deficiency complement deficiency secondary – acquired HIV-AIDS neutropenia leukemia increased – hypersensitivity – alergy anaphylactic cytotoxic immune complexes cell mediated (delayed) T-cell mediated cytotoxicity Immune Disorders Diseases – table of contents • self oriented – autoimmune diseases • Autoimmunity – definition, function • Mechanisms of autoimmune reaction prevention • Autoimmune diseases – representatives • systemic • organ related

  3. 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

  4. 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

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

  6. Nonspecific antibodies immunocomplexes on dendritic cells long lasting antigen presentation Inflammation– immunity

  7. 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

  8. lack of self-tolerance Autoimmunity

  9. constant activity in organogenesis regeneration metalaxia Autoimmunity

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

  11. Three mechanisms of self-tolerance clonal deletion - thymus clonal anergy – APC „off signal“ peripheral suppresion – Ts CD8+ Self x non-self

  12. Mechanisms Preventing Antiself Reactivity: • clonal deletion (thymus) • clonal anergy (thymus) • peripheral clonal supression by Tsupressor cells ( B,T helpers) Protection from protectors….

  13. 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

  14. Lupus erytematodes disseminatus • VASCULITIS • skin – butterfly rash, discoid erythema • mucose membranes ulcers • heart- Liebman-Sacks endocarditis • arthritis • serositis • hemopoietic disorders – hemolytic anemia, leuco-lympho- thrombocyto- penia • kidney – glomerulonephritis • CNS – seizures, psychosis (vascular etiology?) SLE

  15. Rheumatoid arthritis- polyarthritis progressiva primaria chronica • adult women mainly • small joints • morning stiffness • dysfigering, pain, ankylosis • + tendovaginitis, iridocyclitis, vasculitis, lung fibrosis • serum rheumatoid factor – IgM x Fc IgG – immunocomplexes • complication (potentially killing)

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

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

  18. 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.

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

  20. meandr scaning FS ≥ 1

  21. Focus Score morphometry result table

  22. 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

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

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

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

  26. 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´ - Oberhuber´s classification

  27. 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

  28. 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

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

  30. Sclerosis cerebrospinalis multiplex disseminata - virus infection influence(morbilli, herpes, EB) …bacteria?... Pathogenesis • interaction of the macroorganism and virus – limited antibody production (only 10-20% produced viruses are virulent) • virus mutation & immunosupresion (age, pregnancy, stress, other diseases….)

  31. Sclerosis cerebrospinalis multiplex disseminata - virus infection influence2. MS – viral influence (2) • Pathogenesis • infection of endothelia – microangiitis • blood-brain- barrier disorder • serum & CSF CD4, CD8 (miror image to AIDS)

  32. Immune Disorders Diseases Morphology • alteration up to necrosis • NG + lymphoplasmocellular infiltration • fibrosis Prognosis • important in terms of both morbidity and mortality – possible lethal outcome

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