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Immunodeficiency Diseases

  • Overview

    • Caused by immune system abnormalities

      •  Congenital

      •  Acquired (drug treatment, bacterial, viral infections)

    • Consequences:

      •  infection: increased susceptibility, prolonged duration, increased severity

  • Congenital Immunodeficiency Disease:

    • X-linked agammaglobulinemia

      •  affects males;

      •  immature B lymphocytes do not mature into antibody producing plasma cells

      •  cell-mediated immune responses (against fungi/viruses) maintained

    • DiGeorge's syndrome

      •  Thymic failure to develop

        • reduced T cell responses (TDTH, CTL)

    •  Severe Combined Immunodeficiency Disease (SCID)

      • caused by adenosine deaminase (ADA) deficiency

      •  ADA deficiency results in accumulation of apparently toxic deoxyATP in lymphocytes death of T & B cells

      • Successful Treatment Approaches:

        •  purified ADA infusion

        •  ADA gene-modified lymphocyte transfer

    • AIDS --an example of acquired immunodeficiency disease -- caused by the human immunodeficiency virus (HIV)

      • HIV:

        • Significant tropism for CD4+ helper T cells

        • Following CD4+ helper T cell depletion:

          •   opportunistic infection

          •   malignancies

          •  due to inability of T helper cells to maintain cytotoxic lymphocyte response

            • Imbalance develops between TH1 and TH2 cells develops causing:

              •  loss of cytotoxic lymphocyte activity

              •  loss of delayed hypersensitivity

              •  hypergammaglobulinemia

 

Immunocompetency Testing

 

Immunosuppressive Therapy And Cancer Chemotherapy

 

Drug Treatment in the two cases: Different principles

  • Cancer: cell proliferation: unstimulated

  •  Immune cells proliferation: response to specific antigen

  • Cancer: individual cell division -- random, unsynchronized

  • Immune cell proliferation: partially synchronized -- burst of mitotic division (after antigen introduction)

  • afterwards, many responding cells going through a conherent cycle to produce specific immunity.

  • Cytotoxic drugs: selective toxicity difficult

  • Cytotoxic drugs: used at time of initial exposure to foreign antigen (kidney transplant) more effective because:

    •  a high percentage of a small number of precursor cells can be destroyed

    •  the antigen stimulates selected relevant clones to proliferate rather than all clones of immune cells, allowing more selective toxicity

  • Cytotoxic drugs for cancer chemotherapy:

    • high-dosage, "pulse" drug courses

      • allows immune system recovery between treatments

      • not a desirable drug sequence for immunosuppression

  • Cytotoxic drugs for immunosuppression:

    • low dose, continuously to block immunoproliferation (antigenic stimulus persists)

    • must inactivate existing effector cells & suppress tissue immmune response inflammation

 

Primary Source: Barbuto, J.A.M, Akporiaye, E.T. and Hersh, E.M. Immunopharmacology, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 916-940
Haynes, B. F., Fauci, A.S. Disorders of the Immune System, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1753-1776.
Carpenter, C. B. The Major Histocompatibility Gene Complex, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1777-1782.
Cooper,M.D, and Lawton III, A. R. Primary Immune Deficiency Diseases, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1783-1791.
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