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AIDS


   Megha J Nair
   6th Batch
INTRODUCTION

   Acquired Immunodeficiency Syndrome




   First indication in 1981 with reports from
    New York and Los Angeles-sudden outbreak
    of two rare diseases-kaposi’s sarcoma and
    Pnuemocystis carinii
HUMAN IMMUNODEFICIENCY VIRUS
 Causative agent of AIDS
 Spherical enveloped virus about 90-120 nm in
  size
 Genome is diploid composed of two identical
  single stranded positive RNA copies
 Along with viral RNA – reverse transcriptase
  enzyme-characteristic feature of retrovirus
 When virus infects cell-reverse trancriptase
  transcribe the single stranded RNA to double
  stranded RNA nand then to double stranded
  DNA(PROVIRUS)-integrates into human
  genome!
   During viral replication , when the virus buds out of
    the host cell surface membrane-acquires a lipoprotein
    envelop-consists of lipid derived from the host cell
    membrane and glycoproteins which are virus coded

   Major virus coded envelop protein –projecting knob
    like spikes and anchoring transmembrane pedicles

   Spikes-major surface component of virus which binds
    to CD4 receptors on host cells…transmembrane
    proteins help in cell fusion
PATHOGENESIS
 Transmitted mainly through sexual contact or
  through blood transfusion
 Transmitted when the virus enters the blood or
  the tissues and come in contact with suitable
  host cells
 Receptor for virus –CD4 antigen-thus infect any
  cells bearing CD4 antigen on surface-primarily
  the CD4+ helper T cell
 Others include B lymphocytes,monocytes and
  macrophages such as specialised macrophages
  of lungs langerhan cells in dermis.
 After fusion of virus with the cell-HIV genome
  uncoated and internalised into the cell
 Action of reverse transcriptase enzyme-double
  stranded DNA integrated into the human
  genome with the help of integrase-causes
  latent infection
 Long and variable incubation period is due to
  latency
 Primary pathogenic mechanism-due to
  damage caused to the CD4 T lymphocytes
 T4 cells decrease in number,CMI reduces
 T4:T8 ratio reverses
 Helper T cell function-essential for B cell
  function-polyclonal activation of Bcells -
  hypergammaglobulinemia
CLINICAL MANIFESTATIONS

   Not primarily to viral cytopathology but due to
    failure of immune responses




   AIDS – only the last stage in the wide
    spectrum of clinical features
STAGES OF EVOLUTION
   Acute HIV infection

   Asymptomatic or latent infection

   Persistent generalised lymphadenopathy

   AIDS related complex

   AIDS
ACUTE HIV INFECTION
   Within 3-6 weeks of infection

 Low grade fever,malaise,head
  ache,lymphadenopathy,sometimes with
  rashes arthropathy resembling glandular
  fever.Spontaneous resolution within weeks
 Tests for HIV antibodies negative in early
  stage and get positive during its course-
  seroconversion illness.
ASYMPTOMATIC AND LATENT INFECTION
 Symptomless infection
 Positive HIV antibodies test
 Passes through various stages-CD4
  lymphocytopaenia,minor oppurtunistic
  infection,persistent generalised
  lymphadenopathy,ARC and full blown AIDS
 Viral multiplication goes on-immune response
  mounnted by host-only helps in limiting viral
  load
 Tcell-500 from 1000/microlitre-acute infection
  and when 200 or less , clinical AIDS
PGL
   Enlarged lymph nodes


   Atleast 1 cm or more


   In two or more non contiguous extrainguinal
    sites-that persists for more than 3 months in the
    absence of any current illness or medication
PGL
ARC
   Patients with considerable immunodeficiency
    suffering from various constitutional symptoms
    or minor oppurtunistic infections

   Fatigue , unexplained fever , persistent diarrhoe
    , marked weight lose-symptoms-also gen.
    lymphadenopathy and splenomegaly

   Oppurtunistic inf.-oral candidiasis,herpes
    zoster,hairy cell luekoplakia,salmanellosis or tb
ORAL THRUSH
AIDS

•   End stage disease-irreversible breakdown of
    immune system-progressive oppurtunistic
    infection and malignancies.

•   Dry cough , dyspnea , fever , recurrent
    pneumonia

•   GIT-thrush , herpetic steatites , gingivitis , hairy
    luekoplakia or kaposi’s sarcoma.A characteristic
    intestinal pathogen is cryptosporidium
HAIRY LEUKOPLAKIA
   CNS-toxoplasmosis and
    cryptococcosis,lymphomas of CNS also
    seen.also can cross blood brain barrier and
    cause encephalopathy leading to loss of
    higher function-then dementia

   Malignancies-kaposi’s
    sarcoma(nonmetastasing mucosal or
    cutaneous tuour of endothelial orgin)Hodgkin
    and Non Hodgkin lymphomas


   Babies born to infected mothers-also
    positive-
KAPOSI’S LESIONS
DIAGNOSIS
 IMMUNOLOGICAL TESTS:
 Total luecocyte and lymphocyte count
 Tcell subset assay-ratio inversion.Absolute
  CD4 cell count less than 200/cubic mm
 Platelet cout will show thrombocytopaenia
 Raised IgG and IgA levels
 Diminished CMI by skin tests
 Lymph node biopsy
 Specific tests:
 Antigen detection:major core antigen-
  p24-earliest marker-p24 antigen capture
  assay

   Viral isolation:cocultivation of patient’s
    lymphocyte with uninfected lymphocyte in
    the presence of interluekin 2.viral replicatio
    detected by demo of reverse transcriptase
    activity as well as antigen

   PCR:golden standard for diagnosis of all
    stages of HIV infection
 Antibody detection:
 ELISA Test



   Western blot test-HIV proteins seperated
    by their electrophoretic mobility by poly
    acrylamide gel electrophoresis are blotted
    on to the strips of nitrocellulose
    paper.strips are reacted with test sera and
    then with enzyme conjugated anti human
    globulin
TREATMENT

Treatment and prophylaxis of infections and
  tumours
General management
Immunorestortive measures(administration of
  interluekin 2,thymic factors etc)
Specific anti-HIV drugs(anti retroviral drugs)
AIDS: A Deadly Virus

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AIDS: A Deadly Virus

  • 1. AIDS Megha J Nair 6th Batch
  • 2. INTRODUCTION  Acquired Immunodeficiency Syndrome  First indication in 1981 with reports from New York and Los Angeles-sudden outbreak of two rare diseases-kaposi’s sarcoma and Pnuemocystis carinii
  • 3. HUMAN IMMUNODEFICIENCY VIRUS  Causative agent of AIDS  Spherical enveloped virus about 90-120 nm in size  Genome is diploid composed of two identical single stranded positive RNA copies  Along with viral RNA – reverse transcriptase enzyme-characteristic feature of retrovirus  When virus infects cell-reverse trancriptase transcribe the single stranded RNA to double stranded RNA nand then to double stranded DNA(PROVIRUS)-integrates into human genome!
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  • 6. During viral replication , when the virus buds out of the host cell surface membrane-acquires a lipoprotein envelop-consists of lipid derived from the host cell membrane and glycoproteins which are virus coded  Major virus coded envelop protein –projecting knob like spikes and anchoring transmembrane pedicles  Spikes-major surface component of virus which binds to CD4 receptors on host cells…transmembrane proteins help in cell fusion
  • 7. PATHOGENESIS  Transmitted mainly through sexual contact or through blood transfusion  Transmitted when the virus enters the blood or the tissues and come in contact with suitable host cells  Receptor for virus –CD4 antigen-thus infect any cells bearing CD4 antigen on surface-primarily the CD4+ helper T cell  Others include B lymphocytes,monocytes and macrophages such as specialised macrophages of lungs langerhan cells in dermis.
  • 8.  After fusion of virus with the cell-HIV genome uncoated and internalised into the cell  Action of reverse transcriptase enzyme-double stranded DNA integrated into the human genome with the help of integrase-causes latent infection  Long and variable incubation period is due to latency  Primary pathogenic mechanism-due to damage caused to the CD4 T lymphocytes  T4 cells decrease in number,CMI reduces  T4:T8 ratio reverses  Helper T cell function-essential for B cell function-polyclonal activation of Bcells - hypergammaglobulinemia
  • 9. CLINICAL MANIFESTATIONS  Not primarily to viral cytopathology but due to failure of immune responses  AIDS – only the last stage in the wide spectrum of clinical features
  • 10. STAGES OF EVOLUTION  Acute HIV infection  Asymptomatic or latent infection  Persistent generalised lymphadenopathy  AIDS related complex  AIDS
  • 11. ACUTE HIV INFECTION  Within 3-6 weeks of infection  Low grade fever,malaise,head ache,lymphadenopathy,sometimes with rashes arthropathy resembling glandular fever.Spontaneous resolution within weeks  Tests for HIV antibodies negative in early stage and get positive during its course- seroconversion illness.
  • 12. ASYMPTOMATIC AND LATENT INFECTION  Symptomless infection  Positive HIV antibodies test  Passes through various stages-CD4 lymphocytopaenia,minor oppurtunistic infection,persistent generalised lymphadenopathy,ARC and full blown AIDS  Viral multiplication goes on-immune response mounnted by host-only helps in limiting viral load  Tcell-500 from 1000/microlitre-acute infection and when 200 or less , clinical AIDS
  • 13. PGL  Enlarged lymph nodes  Atleast 1 cm or more  In two or more non contiguous extrainguinal sites-that persists for more than 3 months in the absence of any current illness or medication
  • 14. PGL
  • 15. ARC  Patients with considerable immunodeficiency suffering from various constitutional symptoms or minor oppurtunistic infections  Fatigue , unexplained fever , persistent diarrhoe , marked weight lose-symptoms-also gen. lymphadenopathy and splenomegaly  Oppurtunistic inf.-oral candidiasis,herpes zoster,hairy cell luekoplakia,salmanellosis or tb
  • 17. AIDS • End stage disease-irreversible breakdown of immune system-progressive oppurtunistic infection and malignancies. • Dry cough , dyspnea , fever , recurrent pneumonia • GIT-thrush , herpetic steatites , gingivitis , hairy luekoplakia or kaposi’s sarcoma.A characteristic intestinal pathogen is cryptosporidium
  • 19. CNS-toxoplasmosis and cryptococcosis,lymphomas of CNS also seen.also can cross blood brain barrier and cause encephalopathy leading to loss of higher function-then dementia  Malignancies-kaposi’s sarcoma(nonmetastasing mucosal or cutaneous tuour of endothelial orgin)Hodgkin and Non Hodgkin lymphomas  Babies born to infected mothers-also positive-
  • 21.
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  • 23. DIAGNOSIS  IMMUNOLOGICAL TESTS:  Total luecocyte and lymphocyte count  Tcell subset assay-ratio inversion.Absolute CD4 cell count less than 200/cubic mm  Platelet cout will show thrombocytopaenia  Raised IgG and IgA levels  Diminished CMI by skin tests  Lymph node biopsy
  • 24.  Specific tests:  Antigen detection:major core antigen- p24-earliest marker-p24 antigen capture assay  Viral isolation:cocultivation of patient’s lymphocyte with uninfected lymphocyte in the presence of interluekin 2.viral replicatio detected by demo of reverse transcriptase activity as well as antigen  PCR:golden standard for diagnosis of all stages of HIV infection
  • 25.  Antibody detection:  ELISA Test  Western blot test-HIV proteins seperated by their electrophoretic mobility by poly acrylamide gel electrophoresis are blotted on to the strips of nitrocellulose paper.strips are reacted with test sera and then with enzyme conjugated anti human globulin
  • 26. TREATMENT Treatment and prophylaxis of infections and tumours General management Immunorestortive measures(administration of interluekin 2,thymic factors etc) Specific anti-HIV drugs(anti retroviral drugs)