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Pharm immuno19 immunodeficiency

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Pharm immuno19 immunodeficiency

  1. 1. Pharmacy-Immunology 19 Primary & Acquired Immunodeficiency Saber Hussein
  2. 2. Objectives <ul><li>Know the types of primary (congenital) immunodeficiency that result of: </li></ul><ul><ul><li>Defects in B and T lymphocytes maturation </li></ul></ul><ul><ul><li>Defects in lymphocytes activation and function </li></ul></ul><ul><ul><li>Defects in innate immunity </li></ul></ul><ul><ul><li>Lymphocyte abnormalities associated with other diseases </li></ul></ul><ul><li>Know the acquired (secondary) immunodeficiency syndrome (AIDS) in regard of: </li></ul><ul><ul><li>Structure and biology of HIV </li></ul></ul><ul><ul><li>Clinical features of HIV infection and pathogenesis of AIDS </li></ul></ul><ul><ul><li>AIDS therapeutic and vaccination strategies </li></ul></ul>
  3. 3. Features of immunodeficiency diseases <ul><li>Diagnostic features and clinical manifestations of immune deficiencies affecting components of the immune system </li></ul><ul><li>Different diseases, and even different patients with the same disease, may show considerable variation </li></ul>Fig12-1 (Extracellular bacterial infections)
  4. 4. Congenital immunodeficiencies <ul><li>Primary Immunodeficiencies are congenital diseases caused by genetic defects that inhibit maturation of B or T cells or interfere with functions of immune components </li></ul><ul><li>Prevalence : 1 in 500 American and European </li></ul><ul><li>Hallmark of immunodeficiencies’ consequences: </li></ul><ul><ul><li>Infections that could be mild or severe, start in early childhood or in adulthood </li></ul></ul>
  5. 5. Congenital immunodeficiencies caused by defects in lymphocyte maturation <ul><li>Autosomal SCID (severe combined immunodeficiency) caused by: </li></ul><ul><ul><li>ADA (adenosine deaminase) & PNP (purine nucleoside phosphorylase) deficiency prevent maturation of: </li></ul></ul><ul><ul><ul><li>Stem cell  pro-B cell </li></ul></ul></ul><ul><ul><ul><li>Pro-B cell  pre-B cell </li></ul></ul></ul><ul><ul><ul><li>Stem cell  pro-T cell </li></ul></ul></ul><ul><ul><ul><li>Pro-T cell  pre-T cell </li></ul></ul></ul><ul><ul><li>RAG (recombination activating gene) deficiency prevents maturation of: </li></ul></ul><ul><ul><ul><li>Pro-B cell  pre-B cell </li></ul></ul></ul><ul><ul><ul><li>Pro-T cell  pre-T cell </li></ul></ul></ul><ul><li>X-linked SCID: </li></ul><ul><ul><li>Signaling IL-2Rg chain (  c is common in IL receptors of IL-2, IL-4, IL-7 , IL-9, IL-15) deficiency interferes with </li></ul></ul><ul><ul><ul><li>Pro-T cell  pre-T cell [see Fig12-2, next slide] </li></ul></ul></ul>
  6. 6. Fig12-2:Congenital immunodeficiencies Fig12-2:Congenital immunodeficiencies
  7. 7. Features of congenital immunodeficiencies caused by defects in lymphocyte maturation Fig12-3
  8. 8. Features of congenital immunodeficiencies caused by defects in lymphocyte maturation Fig12-3
  9. 9. Congenital immune-deficiencies associated with defects in lymphocyte activation and effector functions <ul><li>Congenital immunodeficiencies may be caused by genetic defects in the expression of molecules required for </li></ul><ul><ul><li>Ag presentation to T cells , </li></ul></ul><ul><ul><li>T or B lymphocyte antigen receptor signaling , </li></ul></ul><ul><ul><li>helper T cell activation of B cells and macrophages , and </li></ul></ul><ul><ul><li>differentiation of antibody-producing B cells . </li></ul></ul>Fig12-4 : Sites where immune responses may be blocked
  10. 10. Congenital immunodeficiencies associated with defects in lymphocyte activation and effector functions Fig12-4: Features of some of resulting deficiency disorders
  11. 11. Congenital immunodeficiencies caused by defects in innate immunity Fig 12-5
  12. 12. Congenital immunodeficiencies caused by defects in innate immunity Fig 12-5
  13. 13. Acquired (secondary) immunodeficiency diseases Fig 12-6
  14. 14. HIV life cycle Fig 12-8 HIV life cycle
  15. 15. The pathogenesis of HIV-AIDS <ul><li>The stages of HIV disease correlate with a progressive spread of HIV from the initial site of infection to lymphoid tissues throughout the body. </li></ul><ul><li>The immune response of the host temporarily controls acute infection but does not prevent establishment of chronic infection of cells in lymphoid tissues. </li></ul>12-9
  16. 16. The pathogenesis of HIV-AIDS <ul><li>The host’s immune response temporarily controls acute infection </li></ul><ul><li>But establishment of chronic infection of cells in lymphoid tissues succeeds </li></ul><ul><li>Cytokines produced in response to HIV and other microbes serve to enhance HIV production and progression to AIDS </li></ul>12-9
  17. 17. The clinical course of HIV disease <ul><li>Blood-borne HIV virus (plasma viremia) is detected early after infection </li></ul><ul><li>It may be accompanied by systemic symptoms typical of acute HIV syndrome </li></ul><ul><li>The virus spreads to lymphoid organs , but </li></ul><ul><li>plasma viremia falls to very low levels (only detectable by sensitive reverse transcriptase polymerase chain reaction (rtPCR) assays) & stays this way for many years </li></ul><ul><li>CD4 + T cell counts steadily decline during this clinical latency period , because of </li></ul><ul><ul><li>active viral replication and </li></ul></ul><ul><ul><li>T cell destruction in lymphoid tissues </li></ul></ul><ul><li>As the level of CD4 + T cells falls , there is increasing risk of infection and other clinical components of AIDS </li></ul><ul><li>[See next slide, Fig 12-10 ] </li></ul>
  18. 18. The clinical course of HIV disease Fig 12-10

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