Cell-mediated immune responses


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Cell-mediated immune responses

  1. 1. Cell-Mediated immune responses (Basic Immunology) 15/07/52
  2. 2. scope -Phases of T Cell Responses -Antigen Recognition and Costimulation -Functional Responses of T Lymphocytes to Antigens and Costimulation -T Cell Signal Attenuation -Migration and retention of effector T cells at site of infection
  3. 3. Phases of T Cell Responses
  4. 4. Antigen Recognition and Costimulation
  5. 5. TCR complex and its restriction
  6. 6. Components of TCR complex
  7. 7. Ag receptor of γδT cells -TCR γ & δ chain consist of extracellular Ig-like V & C regions, hydrophobic transmembrane segment, short cytoplasmic tail เช่นเดียวกับ TCR αβ But not express CD4/CD8 -มักพบใน epithelial tissue (intraepithelial lymphocyte) -recognition : hypothesis recognize Ag ที่พบบ่อยบน epithelial boundaries between host & external environment
  8. 8. Structure of CD4 and CD8 coreptor
  9. 9. Costimulatory receptors of CD28 & CD2 families &their ligand
  10. 10. Role of costimulators in T cell activation -2nd signal -absense : fail to respond & die by apoptosis or enter state of unresponsiveness (anergy) -increase production of IL-2 & stabilize IL-2 mRNA -promote survival of T cell
  11. 11. Role of costimulators in T cell activation 1).CD28 bind to B7-1(CD80), B7-2(CD86) on APC (dendritic cell, macrophage), B cell 2).ICOS(inducible costimulator) : activate production of IL-10 3)CTLA-4(CD152) : self tolerance
  12. 12. Others accessory molecule on T cells -CD44 acidic sulfated membrane glycoprotein : mature T cell, thymocyte, B cell, macrophage, granulocyte, erythrocyte, fiboblasts -bind to hyaluronate : retention T cell in extravascular tissue at infection site -binding of activated & memory T cell to endothelium at site of inflammation, in mucosal tissue
  13. 13. Others accessory molecule on T cells (con.) -CD40 ligand express บน activated CD4 T cell bind to CD40 บน B cell, macrophage, dendritic cell, endothelial cell -Ligand for Fas (CD95) -apoptosis -important for eliminating T cell that are repeated stimulated by Ag
  14. 14. Accessory molecules of T lymphocyte
  15. 15. Ligand-receptor pairs involved in T cell activation
  16. 16. Regulation of integrin avidity
  17. 17. Clonal expansion (proliferation)
  18. 18. Signal transduction pathways in T lymphocyte
  19. 19. Early tyrosine phosphorylation events in T cell activation
  20. 20. Early tyrosine phosphorylation events in T cell activation
  21. 21. T cell signaling downstream of PLCγ1
  22. 22. Ras-Map kinase pathway in T cell activation
  23. 23. Activation of transcription factors in T cell
  24. 24. T cell signal attenuation ทำำได้ 3 วิธี 1).activation inhibitory receptor of CD28 2).tyrosine-phospatases (SHP-1) 3).protein known as E3 ubiquitin ligases
  25. 25. T cell signal attenuation
  26. 26. Ubiquitin ligase Cbl-b in terminating T cell responses
  27. 27. Differentiation of naïve T cell into effector cell
  28. 28. Development of Th1 and Th2 subset
  29. 29. Cytokine signaling by the Jak-STAT pathway
  30. 30. Characteristics of subsets of CD4+ T cell
  31. 31. Effector function of Th1 cells
  32. 32. Effector function of Th2 cells
  33. 33. Activation of CD8+ T cells
  34. 34. Differentiation of CD8 T cell into CTL -ต้องกำร IL-12 -transcription factor : T-bet & eomesodermin -differentiated CTL secrete cytokine, mostly IFN-γ, lymphotoxin, TNF -cascade in differentiation same as CD4
  35. 35. Effector of CD8+ T cell steps in CTL-mediated lysis of target cell
  36. 36. Mechanisms of CTL-mediated lysis of target cells
  37. 37. Action and functions of macrophages in CMI
  38. 38. Migration and retention of effector T cells at site of infection
  39. 39. Migration of naïve and effector T lymphocytes
  40. 40. Recruitment of leukocyte at infection site
  41. 41. T cell homing receptors and their ligands
  42. 42. Thank you for your attention