بسم الله الرحمن الرحيم

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 H2O2 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