• 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 (T_DTH [T-cell-mediated delayed-type hypersensitivity], CTL)

  •  Severe Combined Immunodeficiency Disease (SCID)

    • Caused by adenosine deaminase (ADA) deficiency

    • ADA deficiency results in accumulation of apparently toxic deoxyATP in lymphocytes leading to death of T and 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

  • Delayed hypersensitivity testing

    • Skin test antigens; evaluate immune system ability to recall antigens

  • Direct measurement of:

    • Serum immunoglobulins

    • Serum complement

    • Specific antibodies for acquired/natural antigens

  • Serial measurements of antibody response after:

    • Primary immunization

    • Secondary booster

  • Total circulating lymphocytes

  • Circulating blood lymphocytes distributions

    • Percentages of B cells

    • Percentages of T cells

      • Subsets (e.g. monoclonal antibodies)

  • In vitro lymphocyte profilerative responses to mitogens (response evaluated by quantifying cytokine production or thymidine incorporation)

    • Concanavalin A

    • Phytohemagglutinin

    • Pokeweed mitogen

    • Pther antigens of interest

  • NK cell cytotoxicity® tumor cells (target)

  • Mixed lymphocytes reactions

  • LAK (lymphokine activated killer) cell generation following in vitro IL-2 stimulation

Immunosuppressive Therapy and Cancer Chemotherapy