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

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

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

7. Phases of Inflammatory Response v alteration v exsudation v proliferation

8. Phases of Inflammatory Response Alteration Exsudation Proliferation

9. Phases of Inflammatory Response Alteration Exsudation Proliferation

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 ----------  leucocyte emigration

12. 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

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

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

15. Main Inflammatory Mediators Vasodilation prostaglandins, NO Permeability vasoactive amins, C3,C5, bradykinin Chemotaxis C5a, 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. Mechanisms of Immune Response v nonspecific v antigen specific v humoral v cellular

18. v nonspecific v PHAGOCYTOSIS v bactericid substances (lysozym) v complement v interferon v 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. Cytokines Source: macrophages APC T- lympho Types: growth fcs. colony stim. fcs. chemokins (interleukins) TNFα, TNF β – LT interferons

21. Interleukin 4  Th 2 stimulation – antibody mediated immune response  Th 1 + interferon γ suppresion  inhibition of the T-lymphocytes proliferation  inhibition of TNF α +Il6 secretion

22. v antigen specific v humoral B– lymphocytes v cellular T– lymphocytes INTERACTION B-lympho–T h – affinity maturation – plasmocyte Mechanisms of Immune Response

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

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

25. Heparinocyte degranulation  physical – heat, mech.,UV light,x- rays  chemical –venoms, enzymes  immune – IgE binding, complement

26. 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.)

27.  ingestion & digestion of bacteria  H 2 O 2 & myeloperoxidase  lysozyme - mucopeptide digestion DEATH in a few hours  elastase, colagenase  plasminogen activator  complement activation Neutrophilic granulocytes

28. 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

29. 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 & H 2 O 2 defects –recidives of staphylococcus and aspergillus infection

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

31. Mechanisms of Immune Response v antigen specific v cellular T– lymphocytes APC – CD8+ precursors – T h,T c

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

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

34. Macrophages - secretion  acid & neutral proteases  cytokins IL-1, TNF  O 2, NO  complement components

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

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

37. 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 Inflammation Development