• 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, CTL)

  •  Severe Combined Immunodeficiency Disease (SCID)

    • caused by adenosine deaminase (ADA) deficiency

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

    • Successful Treatment Approaches:

      •  purified ADA infusion

      •  ADA gene-modified lymphocyte transfer

  • AIDS represents 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

  • Other 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