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  • 1. بسم الله الرحمن الرحيم The immunology of HIV infection In : Medical, health and social aspects of HIV/AIDS Sayad B. M.D, MPH 2003
  • 2. Entry of HIV to target cells:(1)
    • Receptors & Ligands
    • HIV receptor and co-receptors
    • CC-chemokines and chemokin receptors
    • Chemokine receptors as HIV co-receptors:
            • CCR5
            • CXCR4
            • Others(CCR1,CCR2b,CCR3)
  • 3. Entry of HIV to target cells:(2)
    • HIV strains and their’s co-receptors:
        • M-tropic strain :CCR5
        • T-tropic strain: CXCR4
    • Natural ligands of CCR5:
        • MIP-1a
        • MIP-1b
        • RANTES
    • Natural ligand of CXCR4:
        • SDF-1
  • 4. Entry of HIV to target cells:(3)
    • Answer the questions:
        • 1.What is the result of HIV infection in the presence of natural ligands of HIV co-receptors?
        • 2.Can we use chemokins as a treatment in HIV infections?
        • 3.What is the result of CCR5 defect?
  • 5. Entry of HIV to target cells:(4)
    • HIV co-receptor defects:
          • CCR5-delete 32
          • CCR5-delete 32/m303
          • CCR2 defect
          • SDF-1 3’A
  • 6. Entry of HIV to target cells:(5)
      • Expression of HIV-coreceptors:
        • For example CCR5:
          • Upregulation: with IL-2
          • Downregulation: with CD3,CD28 stimulation
  • 7. Entry of HIV to target cells:(6)
      • New therapeutic strategies:
        • Chemokine analogues
        • Molecular genetic approach
  • 8. Immune responses to HIV:
        • Immune responses is severe and universal
        • Some responses maybe harmful to the host
  • 9. Immune dysfunction during HIVinfection:
        • CD4+ Tcells
        • CD8+ Tcells
        • Monocytes-macrophages
        • Dendritic cells
        • B lymphocytes
        • Neutrophils
        • Natural killer cells
  • 10. CD4+ Tcells dysfunction:
    • Direct mechanisms:
      • Accumulation of unintegrated viral DNA
      • Interference with cellular RNA processing
      • Intracellular gp120 autofusion events
      • Viral budding
      • Elimination of HIV infected cells
    • Indirect mechanisms:
      • Syncytium formation
      • Autoimminity
      • Superantigenetic stimulation
      • Innocent by stander killing
      • Apoptosis
  • 11. CD8+ Tcells:
        • Roles in defense against HIV infection
        • Dysregulation of CD8+ Tcell numbers
        • Cytotoxicity dysfunction
        • Abnormal phenotypes:
            • HLA-DR with CD38
            • HLA-Drwithout CD38
  • 12. Monocytes-Macrophages:
        • Roles in the immunophathogenesis of HIV
        • Decreased MHC-II expression
        • Decreased IL-12 secretion
        • Increased IL-10 secretion
        • Defects in the ADCC
        • Abnormal Ag uptake
        • Abnormal oxidative burst
        • Abnormal chemotaxis
  • 13. B cells:
        • Hypergammaglobulinemia
        • B cells hyperactivation
        • Decreased ability to response to Ag
        • Decreasd HLA-DR Expression
        • Secretion of TNF-a and IL-6
  • 14. Neutrophils:
      • Increased in NBT reduction
      • Increased oxydative capacity with GM-CSF
      • Increased actin polimerization
      • Increased H 2 O 2 production
      • Increased oxygen radical production
      • Decreased opsonization activity
      • Accelerated apoptosis
      • Overproduction of TNF-a ,IL-6
  • 15. Natural Killer Cells:
      • Roles in defense against HIV:
          • ADCC
          • Secretion of inhibtory chemokines
      • Decreased CD16+/CD56+ subpapulation
      • Decreased ability of killing targets
  • 16. Dendritic cells:
    • Roles in defense against HIV
    • Impair the ability to activate Tcells
  • 17. Manifestations of an activated immune system in HIV:
      • Hyperactivation of Bcells
      • Hypergammaglobulinemia
      • Spuntaneous lymphocytic proliferation
      • Activation of monocytes with cytokines
      • Increased activation markers on Tcells
      • Follicular hyperplasia
      • Autoimmunity
  • 18. Cytokines and HIV infection:
      • Cytokines that cause increased replication:
          • TNF-a,TNF-b-, G-CSF, GM-CSF
          • IL-1b, IL-2, IL-3, IL-6
          • IL-7, IL-12, IL-15
      • Cytokines that cause decreased replication:
          • INF-a, INF-b, IL-16
      • Cytokines that cause increased or decreased replication:
          • IL-4, IL-10, IL-13
          • INF-Y TGF-b
  • 19. Cytokines and therapeutic interventions:
    • TNF inhibition with pentoxyfylline
    • IL-2 plus HAART for increase CD4+T cells
    • IL-2 plus IL-16 for expansion of CD4+T cells
  • 20. شاد باشيـــد