• Like
Inflammation 3
Upcoming SlideShare
Loading in...5
×

Inflammation 3

  • 986 views
Uploaded on

Designed for UG pathology teaching.

Designed for UG pathology teaching.

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
No Downloads

Views

Total Views
986
On Slideshare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
97
Comments
0
Likes
3

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. Inflammationand Repair - 3 Dr.CSBR.Prasad, M.D. V3-CSBRP-Apr-2012
  • 2. DIAPEDESIS (Transmigration)Migration of Leukocytes through the interendothelial gaps V3-CSBRP-Apr-2012
  • 3. Diapedesis• It occurs mostly thru post capillary venules• Chemokines stimulate the PMNs to emigrate in to interstitium• PMNs leave the vessel thru inter endothelial gaps• In the interstitium they travel towards the site of injury V3-CSBRP-Apr-2012
  • 4. Adhesion molecules (AM) involved in diapedesis• AM present in between the endothelial cells and in the interstitium facilitate this process• These include: PECAM-1 or CD31 Several junctional AMs V3-CSBRP-Apr-2012
  • 5. Diapedesis• Must then cross basement membrane – Collagenases• PMNs secrete collagenases to dissolve basement membrane• Then they reach the site of injury by Chemotaxis V3-CSBRP-Apr-2012
  • 6. Summary of DIAPEDESISInsertion of pseudopodia which widens the intercellular gapsPassage through the gaps by ameboid movementPassage through the basement membrane either by mechanical disruption or possibly by enzyme (collagenase) effect V3-CSBRP-Apr-2012
  • 7. WOW!V3-CSBRP-Apr-2012
  • 8. Neutrophil Transendothelial Migration (Diapedesis) V3-CSBRP-Apr-2012
  • 9. V3-CSBRP-Apr-2012
  • 10. Chemotaxis of Leukocytes V3-CSBRP-Apr-2012
  • 11. ChemotaxisIn the intestitium leucocytes reach the site of injury by traveling along the concentration gradient created by the chemokines - Chemotaxis V3-CSBRP-Apr-2012
  • 12. ChemotaxisDef: Chemotaxis is a process by which the leucocytes travel towards and along the chemical concentration gradient.Concentration gradient is created by chemokinesHighest concentration occurs at the center of injury V3-CSBRP-Apr-2012
  • 13. This is a diagram showing the effect of chemokine concentrationgradient on chemotaxis direction. The attracted cell moves throughthe gradient toward the higher concentration of chemokine. V3-CSBRP-Apr-2012
  • 14. Chemotaxis• Leukocytes follow chemical gradient to the site of injury• Chemotactic agents: include – Soluble bacterial products – Complement components (C5a) – Cytokines (chemokine family e.g., IL-8) – LTB4 (AA metabolite)• Chemotactic agents bind surface receptors inducing calcium mobilization and assembly of cytoskeletal contractile elements V3-CSBRP-Apr-2012
  • 15. V3-CSBRP-Apr-2012
  • 16. Chemotactic substances will bind to leukocyte receptors, initiating a stimulus –receptor interaction that leads to activation of intracellular contractile proteins V3-CSBRP-Apr-2012
  • 17. Leukocytes: – Extend pseudopods with overlying surface adhesion molecules (integrins) that bind ECM during chemotaxis – Leucocytes walk towards the injury V3-CSBRP-Apr-2012
  • 18. ChemotaxisV3-CSBRP-Apr-2012
  • 19. When they reach the site…• PMNs able to adhere to the intercellular matrix by binding of integrins to CD44• By this mechanism they are retained at the site where they are needed most V3-CSBRP-Apr-2012
  • 20. PHAGOCYTOSIS V3-CSBRP-Apr-2012
  • 21. PHAGOCYTOSISIngestion and processing of particulate material by phagocytic cells – Particulate matter can be: • Tissue debri, bacteria, other foreign cells – Phagocytic cells: • PMNs, MØ V3-CSBRP-Apr-2012
  • 22. PHAGOCYTOSISPhagocytic cells are two types: 1. Microphages (neutrophils) or 2. Macrophages (monocytes / histiocytes) V3-CSBRP-Apr-2012
  • 23. PHAGOCYTOSISThe process of phagocytosis involves: 1. Adhesion – Immobilizes the particles 2. Engulfment by extending pseudopodia 3. Fusion of the lysosomes with the phagocytic vacuole 4. Degradation / Intracellular microbial killing V3-CSBRP-Apr-2012
  • 24. PhagocytosisRecognition and Engulfment attachment of the particle to be ingested formation of a phagocytic vacuole Killing degradation V3-CSBRP-Apr-2012
  • 25. Process of Phagocytosis V3-CSBRP-Apr-2012
  • 26. V3-CSBRP-Apr-2012
  • 27. PHAGOCYTOSISThe process of phagocytosis:Adhesion • Collectins, C3b, Fc portion of IgOpsonization:Coating the particle by opsonins  Complement C3b  Immunoglobulins IgGOpsonization facilitates phagocytosis V3-CSBRP-Apr-2012
  • 28. What is C3b and Fc ? V3-CSBRP-Apr-2012
  • 29. V3-CSBRP-Apr-2012
  • 30. V3-CSBRP-Apr-2012
  • 31. PHAGOCYTOSISThe process of phagocytosis:Opsonins:Like sauce making the bread palatable, opsonins make particles palatable for phagocytesOpsonization facilitates phagocytosisPMNs and MØ has receptors for C3b & Fc V3-CSBRP-Apr-2012
  • 32. Activation V3-CSBRP-Apr-2012
  • 33. Activation• When the leucocytes gets stimulated by the cytokines, they get activated• With activation: – AM are modulated / potentiated – Chemotaxis is potentiated – Elaborate AA metabolites – Secretion / Degranulation – Oxidative out burst V3-CSBRP-Apr-2012
  • 34. Activation The biologic activities resulting from leukocyte activation include Chemotaxis Modulation of AM Elaboration of AA Metabolites Secretion / Degranulation Oxidative burstV3-CSBRP-Apr-2012
  • 35. Defects in Leucocyte FunctionCan be genetic / acquiredResults in increased vulnerability to infections• Defects in leucocyte adheshion• Defects in phagolysosome function – Chediak - Higashi syndrome• Defects in microbicidal activity – Chronic Granulomatous Disease V3-CSBRP-Apr-2012
  • 36. Defects in Leucocyte FunctionGENETIC• LAD1 beta chain of CD11/CD18 integrins• LAD2 fucosyl tranferase required for synthesis of sialyated oligosccharide (receptor for selectin)• CGD (decreased oxidative burst) – X-linked (NADPH oxidase – membrane component) – Autosomal recessive (NADPH oxidase - cytoplasmic) – MPO deficiency (absent MPO-H2O2 system)• Chediak-Higashi syndrome (protein involved in organelle membrane fusion) V3-CSBRP-Apr-2012
  • 37. Defects in Leucocyte FunctionACQUIRED• Thermal injury, diabetes, malignancy, sepsis, immunodeficiencies • Chemotaxis• Hemodialysis, diabetes mellitus • Adhesion• Leukemia, anemia, sepsis, diabetes, neonates, malnutrition • Phagocytosis and Microbicidal activity V3-CSBRP-Apr-2012
  • 38. ENDV3-CSBRP-Apr-2012
  • 39. V3-CSBRP-Apr-2012