Immunosuppression refers to the dampening of the immune response by a normal immune system to antigenic stimulation, either deliberately, or as an adverse effect of a therapeutic agent such as anti-neoplastic chemotherapy.
It can also occur when the immune system is impaired such as systemic lupus erythematosus, or diabetes.
Causes of immunosuppression
The causes of immunosuppression may be classified as:
- Diabetes mellitus
- Chronic alcoholism
- Renal or hepatic failure
- Autoimmune disorders such as systemic lupus erythematosus or rheumatoid arthritis
- CNS infection
- Polyclonal immunoglobulins such as antilymphocyte globulin, and monoclonal immunoglobulins such as daclizumab (both monoclonal and polyclonal immunoglobulins target cellular immunity alone by depleting lymphocytes)
- Calcineurin inhibitors which prevent T cell transcription, such as cyclosporine
- Rapamycins which block the mTOR kinase in lymphocytes, such as everolimus
- Mitosis inhibitors which block purine metabolism, such as azathioprine
- Ionizing radiation
- Biological alkylating agents such as cyclophosphamide and chlorambucil
Indications for immunosuppression
Immunosuppression is clinically indicated in three distinct situations:
- The post-transplant period, to prevent graft rejection and graft-versus-host reactions
- The presence of an autoimmune or hypersensitivity disorder which causes self-antigens to be identified as foreign targets of immune attack, and leads to tissue and organ damage, and
- The occurrence of lymphoproliferative disorders.
Immunosuppressants are drugs which are used to intentionally suppress the production and activity of immune cells. However, these drugs also suppress the normal immune response to infectious agents, and even to emerging malignant or pre-malignant changes in cells.
Chemotherapeutic drugs also diminish the normal immune response.
The normal immune response
An immune response has two phases, namely, an inductive and a productive phase. In the inductive phase, small lymphocytes interact with the foreign antigen. In the productive phase, the stimulated cells multiply and also stimulate more cells, as well as producing antibodies from plasma cells, depending on the nature of the cells that are stimulated.
Most immunosuppressants act by preventing the proliferation of immunocompetent cells. Thus they block the primary immune response. The secondary or anamnestic response, which depends upon already formed memory cells, is more difficult to block.
Symptoms and signs of immunosuppression
In general, immunosuppressed patients have an altered relationship with foreign antigens, including those of pathogenic microbes. This brings about the following clinically important changes:
- Opportunistic infections by otherwise harmless organisms. These include:
- Viral infections such as herpes infections, zoster, CMV,
- Bacterial infections such as S. aureus,
- Fungal infections such as Aspergillus,
- Rapid progress of infections,
- Changes in the usual signs and symptoms of infection, including laboratory parameters, leading to atypical presentation of infection, and
- Malignancies such as tumors in graft recipients, or second malignancies in patients being treated with chemotherapy for leukemia.
In addition to systemic infection, the general health of these patients is weakened by many factors, such as:
- the underlying illness,
- adverse drug reactions,
- malnutrition, and
- side effects of various medical procedures.
Diagnosis and treatment
Diagnosis of immunosuppression is by tests of immune function, such as:
- Cellular immunity tests, including:
- Phagocytic function tests such as nitroblue tetrazolium reduction
- Skin testing for delayed hypersensitivity reactions,
- T cell activation tests such as transformation after mitogen exposure, lymphokine assays such as migration inhibition factor
- Humoral immunity tests, such as:
- Serum immunoglobulin assays such as radial immunodiffusion and serum electrophoresis,
- specific antibody quantitative tests such as agglutination, radioimmunoassay or ELISA tests, and
- B cell quantitation
Treatment is aimed at preventing and treating infections as early and aggressively as possible.