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UNIVERSITY OF GONDAR
       COLLEGE OF MEDCINE & HEALTH SCIENCES
        SCHOOL OF BIOMEDICAL & LABORATORY
                     SCIENCES
     DEPARTMENT OF IMMUNOLOGY & MOLECULAR
                     BIOLOGY




           TOPIC: IMMUNITY AGAINST HIV INFECTION



3/9/2013          Med.Micro students               1
Prepared by:
 Abebe Bekele                             Seble Worku
 Alembanch Tsega                          Setegn Eshetie
 Amele work Yilma                         Tesfaye Andualem
 Feleke Mekonen
                                           Tigist Engda
 Melkamu Getnet
                                           Wondossen
 Emebet Sahlie




  3/9/2013           Med.Micro students                        2
Acknowledgment
  We would like to extend our gratitude
     to Mr. Biniyam Matheous; for his
     interactive and participatory teaching
     learning style.




3/9/2013      Med.Micro students              3
Out line
  Introduction
  HIV life cycle
  Components of antiviral response
  Immune pathogenesis of HIV
  Literature review
  Conclusion
  Recommendation
  Reference

3/9/2013    Med.Micro students        4
INTRODUCTION
Family : Retroviridae
Subfamily : Lentivirus
  RNA virus, 120nm in
   diameter
  Envelope gp160; gp120 &
   gp41
  Icosahedral symmetry
  Nucelocapsid
        Outer matrix protein (p17)
        Major capsid protein (p24)
        Nuclear protein (p7)
  Diploid RNA with several
     copies of reverse
     transcriptase

3/9/2013              Med.Micro students   5
Retroviral Genes
  gag (group-specific antigen): makes the cone shape
   viral capsid.
  pol (polymerase): codes for viral enzymes reverse
   transcriptase, integrase, and viral protease.
  env (envelope): makes surface protein gp120 and trans
   membrane gp41, enabling HIV to fuse to CD4 cells.




3/9/2013       Med.Micro students                          6
con…




3/9/2013   Med.Micro students   7
HIV life cycle




3/9/2013   Med.Micro students       8
Component of antiviral response
  Both humoral and cell-mediated immune responses
   partially control the viral production but in this
   process they destroy the infected CD4+T cells,
    leading to a gradual decline of CD4+ T cells
Innate Immunity
     Antigen presenting cells: Macrophage and Dendritic cells
     Other cell types: NK, gamma- delta , NKT cells
     Soluble factors: Chemokines
Adaptive Immunity
     CD4 T helper cells
     CD8 T cells (CTL)
     B cells: Neutralizing     antibodies
    3/9/2013         Med.Micro students                          9
Cont…




3/9/2013   Med.Micro students   10
Pathogenesis of HIV / AIDS
Infected T-Cell

           HIV                          HIV Infected   New HIV
                   T-Cell                 T-Cell        Virus
           Virus




3/9/2013           Med.Micro students                            11
Immune pathogenesis of HIV
  Mechanisms
       syncytium formation
       Apoptosis
       Auto immunity




3/9/2013       Med.Micro students   12
Literature review
  HIV will mount an effective immune
     response to the virus during the first few
     months of infection. However, over time this
     response will prove ineffective.
       Humeral immunity



           Cell
           mediated immunity
  Both are ineffective
3/9/2013           Med.Micro students           13
Cont…
  Mucosal immunity Vs HIV infection
  The study demonstrated that commercial
   sex workers were HIV negative after 5 yrs
   active prostitutions
  Associated with the integrity of mucosal
   immunity.



3/9/2013     Med.Micro students                14
Cont..
  Study indicated that intranasal
   administration of DNA vaccine and IL-15
   expression plasmid is capable of enhancing
   the T helper type 1 (Th1) dependent HIV-1-
   specific cell-mediated immunity, but
  It decrease humoral immunity



3/9/2013     Med.Micro students                 15
Cont…
  DCs are key regulators of both adaptive and
   innate immune responses
  According the study, it revealed that the
   plasma from patients with HIV specifically
   inhibited DC function.
  mediated by elevated apoptotic micro
   particles.

3/9/2013     Med.Micro students                  16
Cont…
  The study confirmed that HIV infection causes
  NK cells apoptosis (increase expression of ki67 and
   Fas markers in course of infection)
  Macrophage and monocyte phenotype change (
   alteration of TLR)
  Causes defect in microbial killing




3/9/2013       Med.Micro students                        17
Cont..
  Depot medroxyprogesterone acetate
   (DMPA) usage relation to HIV immunity.
  Decrease both arms of immunity(interferon
   (IFN)-gamma, IL-2, IL-4, IL-6, IL-12, TNF
   alpha and other cytokines)
  Mediate up regulation of co-
   receptors(CXCR4, CCR5)

3/9/2013    Med.Micro students                 18
Con…
  In contrast: PA-MSHA activates both
   natural and specific immunity
  NK cells, APCs activates through TLR
  More over: serve as adjuvant for HIV-1 DNA
   vaccine. Increase Humeral and Cell mediate
   response



3/9/2013    Med.Micro students                  19
Cont…
  cholesterol-25-hydroxylase (CH25H)
   recognized that a broadly antiviral
   interferon stimulated genes
  Converts cholesterol in to soluble antiviral
   agents; inhibits viral replication
   (attachment)
  Animal model shows: CH25H deficient mice
   more susceptible to HIV-1 infection.
3/9/2013     Med.Micro students               20
Conclusion
  HIV establishes a latent reservoir early in infection
  HIV develops mutations to escape immune
     responses,
  HIV depletes functional cells of innate immune
     system
  HIV depletes CD4 T cells: the “conductor of the
     immune orchestra” and blunts immune responses
  HIV causes deleterious effects on the entire immune
     system resulting in aberrant immune activation

3/9/2013          Med.Micro students                       21
Recommendation
  The mechanism of immune response
   against HIV infection remains
   incompletely understood, so that
  It needs further investigation.
  So that we post graduate students
   should take emphasis in this particular
   researchable area.
3/9/2013    Med.Micro students               22
References

  Hou J, Liu Y, Shao Y. The MSHA strain of
   Pseudomonas aeruginosa activated TLR pathway and
   enhanced HIV-1 DNA vaccine immunoreactivity. PloS
   one. 2012;7(10):e47724. Epub 2012/10/19.
  Poudrier J, Thibodeau V, Roger M. Natural Immunity
   to HIV: A Delicate Balance between Strength and
   Control. Clinical & developmental immunology.
   2012;2012:875821. Epub 2013/01/11.
  And more


3/9/2013       Med.Micro students                       23
3/9/2013   Med.Micro students   24

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Ppt hiv

  • 1. UNIVERSITY OF GONDAR COLLEGE OF MEDCINE & HEALTH SCIENCES SCHOOL OF BIOMEDICAL & LABORATORY SCIENCES DEPARTMENT OF IMMUNOLOGY & MOLECULAR BIOLOGY TOPIC: IMMUNITY AGAINST HIV INFECTION 3/9/2013 Med.Micro students 1
  • 2. Prepared by:  Abebe Bekele  Seble Worku  Alembanch Tsega  Setegn Eshetie  Amele work Yilma  Tesfaye Andualem  Feleke Mekonen  Tigist Engda  Melkamu Getnet  Wondossen  Emebet Sahlie 3/9/2013 Med.Micro students 2
  • 3. Acknowledgment  We would like to extend our gratitude to Mr. Biniyam Matheous; for his interactive and participatory teaching learning style. 3/9/2013 Med.Micro students 3
  • 4. Out line  Introduction  HIV life cycle  Components of antiviral response  Immune pathogenesis of HIV  Literature review  Conclusion  Recommendation  Reference 3/9/2013 Med.Micro students 4
  • 5. INTRODUCTION Family : Retroviridae Subfamily : Lentivirus  RNA virus, 120nm in diameter  Envelope gp160; gp120 & gp41  Icosahedral symmetry  Nucelocapsid  Outer matrix protein (p17)  Major capsid protein (p24)  Nuclear protein (p7)  Diploid RNA with several copies of reverse transcriptase 3/9/2013 Med.Micro students 5
  • 6. Retroviral Genes  gag (group-specific antigen): makes the cone shape viral capsid.  pol (polymerase): codes for viral enzymes reverse transcriptase, integrase, and viral protease.  env (envelope): makes surface protein gp120 and trans membrane gp41, enabling HIV to fuse to CD4 cells. 3/9/2013 Med.Micro students 6
  • 7. con… 3/9/2013 Med.Micro students 7
  • 8. HIV life cycle 3/9/2013 Med.Micro students 8
  • 9. Component of antiviral response  Both humoral and cell-mediated immune responses partially control the viral production but in this process they destroy the infected CD4+T cells, leading to a gradual decline of CD4+ T cells Innate Immunity  Antigen presenting cells: Macrophage and Dendritic cells  Other cell types: NK, gamma- delta , NKT cells  Soluble factors: Chemokines Adaptive Immunity  CD4 T helper cells  CD8 T cells (CTL)  B cells: Neutralizing antibodies 3/9/2013 Med.Micro students 9
  • 10. Cont… 3/9/2013 Med.Micro students 10
  • 11. Pathogenesis of HIV / AIDS Infected T-Cell HIV HIV Infected New HIV T-Cell T-Cell Virus Virus 3/9/2013 Med.Micro students 11
  • 12. Immune pathogenesis of HIV  Mechanisms syncytium formation Apoptosis Auto immunity 3/9/2013 Med.Micro students 12
  • 13. Literature review  HIV will mount an effective immune response to the virus during the first few months of infection. However, over time this response will prove ineffective. Humeral immunity Cell mediated immunity  Both are ineffective 3/9/2013 Med.Micro students 13
  • 14. Cont…  Mucosal immunity Vs HIV infection  The study demonstrated that commercial sex workers were HIV negative after 5 yrs active prostitutions  Associated with the integrity of mucosal immunity. 3/9/2013 Med.Micro students 14
  • 15. Cont..  Study indicated that intranasal administration of DNA vaccine and IL-15 expression plasmid is capable of enhancing the T helper type 1 (Th1) dependent HIV-1- specific cell-mediated immunity, but  It decrease humoral immunity 3/9/2013 Med.Micro students 15
  • 16. Cont…  DCs are key regulators of both adaptive and innate immune responses  According the study, it revealed that the plasma from patients with HIV specifically inhibited DC function.  mediated by elevated apoptotic micro particles. 3/9/2013 Med.Micro students 16
  • 17. Cont…  The study confirmed that HIV infection causes  NK cells apoptosis (increase expression of ki67 and Fas markers in course of infection)  Macrophage and monocyte phenotype change ( alteration of TLR)  Causes defect in microbial killing 3/9/2013 Med.Micro students 17
  • 18. Cont..  Depot medroxyprogesterone acetate (DMPA) usage relation to HIV immunity.  Decrease both arms of immunity(interferon (IFN)-gamma, IL-2, IL-4, IL-6, IL-12, TNF alpha and other cytokines)  Mediate up regulation of co- receptors(CXCR4, CCR5) 3/9/2013 Med.Micro students 18
  • 19. Con…  In contrast: PA-MSHA activates both natural and specific immunity  NK cells, APCs activates through TLR  More over: serve as adjuvant for HIV-1 DNA vaccine. Increase Humeral and Cell mediate response 3/9/2013 Med.Micro students 19
  • 20. Cont…  cholesterol-25-hydroxylase (CH25H) recognized that a broadly antiviral interferon stimulated genes  Converts cholesterol in to soluble antiviral agents; inhibits viral replication (attachment)  Animal model shows: CH25H deficient mice more susceptible to HIV-1 infection. 3/9/2013 Med.Micro students 20
  • 21. Conclusion  HIV establishes a latent reservoir early in infection  HIV develops mutations to escape immune responses,  HIV depletes functional cells of innate immune system  HIV depletes CD4 T cells: the “conductor of the immune orchestra” and blunts immune responses  HIV causes deleterious effects on the entire immune system resulting in aberrant immune activation 3/9/2013 Med.Micro students 21
  • 22. Recommendation  The mechanism of immune response against HIV infection remains incompletely understood, so that  It needs further investigation.  So that we post graduate students should take emphasis in this particular researchable area. 3/9/2013 Med.Micro students 22
  • 23. References  Hou J, Liu Y, Shao Y. The MSHA strain of Pseudomonas aeruginosa activated TLR pathway and enhanced HIV-1 DNA vaccine immunoreactivity. PloS one. 2012;7(10):e47724. Epub 2012/10/19.  Poudrier J, Thibodeau V, Roger M. Natural Immunity to HIV: A Delicate Balance between Strength and Control. Clinical & developmental immunology. 2012;2012:875821. Epub 2013/01/11.  And more 3/9/2013 Med.Micro students 23
  • 24. 3/9/2013 Med.Micro students 24