1 / 36

General Pathology

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

dremal
Download Presentation

General Pathology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

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

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

  3. Inflammation Sense defensive– agent elimination reparative – damage reparation

  4. Time view acute (days) subacute (weeks) chronic (months-years) Inflammation - Classification:

  5. Causes: nonliving physical chemical Inflammation - Classification: • living viral bacterial mycotic parasitic AUTOIMMUNE

  6. rubor tumor calor dolor functio laesa Inflammation Celsus´ features:

  7. alteration exsudation proliferation Phases of Inflammatory Response

  8. Phases of Inflammatory Response Alteration Proliferation Exsudation

  9. Phases of Inflammatory Response Proliferation Alteration Exsudation

  10. Vascular Changes in Inflammation • Flux hyperemia - axonal reflex • Peristatic hyperemia • Stasis • Increased permeability - exsudation • Inflammatory edema

  11. Active Hyperemia • vasodilatation • slowing of the circulation • increased microvasculature permeability – leakage ---------- • leucocyteemigration

  12. Active Hyperemia • vasodilatation leakage Chemical mediators: Cells: histamine , serotonin, catecholamins, lysosomal enzymes Plasma: complement, kinin system, coagulation/fibrinolysis system

  13. Mast Cell ruling the process • Degranulation(immediate response) • histamin-vasodilation-permeability-exsudation • neutrofil chemotactic factor (micro)fagocytosis • eosinophil chemotactic factor -modulation of the vascular effect • Synthesis (long-term response) • leukotriens (SRS-A) –vasodilation-permeability-exsudation • prostaglandins - vasodilation-permeability-exsudation- PAIN

  14. Active Hyperemia • vasodilatation • slowing of the circulation • increased microvasculature permeability - leakage • leucocyte emigration chemotaxis: • soluble bact. products • complement components esp. C5a • products of lipoxygenase pathway of arachidonic acid (esp.leukotriene B4)

  15. Main Inflammatory Mediators Vasodilationprostaglandins, NO Permeabilityvasoactive amins, C3,C5, bradykinin ChemotaxisC5a, bacterial products, leucotriens, cytokins Fever interleukin 1,6, TNF, prostaglandins Pain prostaglandins, bradykinin Tissue damage lysosomal enzymes…

  16. Mechanisms and Morphological Features of Immune Reaction

  17. nonspecific antigen specific humoral cellular Mechanisms of Immune Response

  18. nonspecific PHAGOCYTOSIS bactericid substances (lysozym) complement interferon proteins distinguishing general microbial structures Mechanisms of Immune Response

  19. Cytokines Def.: polypeptides and proteins - regulatory molecules participating by autocrine, paracrine & endocrine function in homeostasis maintenance

  20. Source: macrophages APC T- lympho Types: growth fcs. colony stim. fcs. chemokins (interleukins) TNFα, TNF β – LT interferons Cytokines

  21. Bradley JR.TNF-mediated inflammatory disease. TNF was originally described (1975) as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response. TNF interacts with two different receptors, designated TNFR1 and TNFR2, TNF stimulation leads to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration. Vascular endothelial cells increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis. J Pathol. 2008 Jan;214(2):149-60

  22. Zhang X, Mosser DM.Macrophage activation by endogenous danger signals. Most microbes have Pathogen Associated Molecular Patterns (PAMPS) that are recognized by macrophages and trigger this activation response. J Pathol. 2008 Jan;214(2):161-78.

  23. Interleukin 4 • Th2 stimulation – antibody mediated immune response • Th1 + interferon γ suppresion • inhibition of the T-lymphocytes proliferation • inhibition of TNF α +Il6 secretion

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

  25. Inflammatory cells • neutrophile granulocytes • eosinophil granulocytes • basophil granulocytes & heparinocytes • lymphocytes & plasmocytes • monocytes – macrophages • erythrocytes • platelets

  26. antigen specific cellular T– lymphocytes APC – CD8+ precursors – Th,Tc Mechanisms of Immune Response

  27. Heparinocytes • IgE receptors • mediators production (heparin, histamin, serototnin, catecholamins…) • cytokin production IL4, TNF α • chemotactic factors for neutrophils & eosinophils

  28. Neutrophilic granulocytes • pavementing(selectins, integrins) • emigration(chemotactic factors from bacteria, complement 3a, 5a, kinins, histamin….) • fagocytosis(both non specific without opsonisation and specific IgG + compl.)

  29. NG disorders 1. • migration & chemotaxis • lazy leucocytes syndrome • diabetes (locomotion) • Chédiak- Higashi syndrome (bacteria killing, lack of elastase, locomotion) • β2-integrin defect (adhaesion) • locomotion • serum changes • corticoids • phenylbutazone

  30. NG disorders 2. • phagocytosis • opsonins & IgG in sickle cell anaemia • morphin abusers • lyzosom fusion (corticoids, antimalaric drugs, CH-H sy… • bactericid effect • chronic granulomatosis in children • cytochrom oxidase & H2O2 defects • recidives of staphylococcus and aspergillus infection

  31. Eosinophilic Granulocytes • alergic response • IgA receptors • anti parasites defence • peroxidase, histaminase, acid phophatase, cytokins

  32. Macrophages - Function • phagocytosis • bacteria killing • mediators production • antigen processing & presentation • modulation of fibroblast proliferation – IL-1 • modulation of endothelia proliferation – TNFα

  33. Macrophages - secretion • acid & neutral proteases • cytokins IL-1 , TNF • O2, NO • complement components

  34. Thrombocytes • mediators production • vasoactive substances, thrombosis, mesenchymal cell proliferation • granules: serotonin, ADP, acid phophatase, thromboxan, Ca cationic protein…

  35. Systemic Inflammatory Response • lymphatic tissue activation • fever – IL 1, prostaglandins • leucocytosis • lymfocytosis in viral infections • eosinophilia in parasitic diseases

  36. Inflammation Development Complete resolution - ad integrum vessel permeability normalized migration stopped necrosis resorption tissue regeneration Healing with a defect - per defectum regeneration impossible – extensive necrosis granulation tissue – scar Progression towards a chronic inflammation

More Related