ملخص

Immunosuppressive Therapy

used for:
1. Hypersensitivity disorders
2. Autoimmune diseases
3. Solid organ transplantation

Types of immunosuppressive drugs/agents

1. Glucocorticosteroids
2. Antiproliferative drugs
3. Calcineurine inhibitors
4. Biological agents

1-Glucocorticosteroids:

Used as an immunosuppressive medication. They have also potent anti-inflammatory effects. Their immunosuppressive effects on the immune system are more prominent on the cellular immunity
B cells: Decrease antibody production in primary immune response and no effect on memory cells (secondary immune response).
monocytes/macrophages:
Decreased numbers of monocytes in the blood, and inhibition of the proinflammatory cytokines production,antigen presentation, and bactericidal activity.


Neutrophils:
Increased numbers in the peripheral blood due to interference with their migration.
T-cells:
Decreased numbers of peripheral blood lymphocytes and in lymphoid tissues in particular CD4 T cells .

The anti-inflammatory effect is through the inhibition of arachidonic acid metabolites

The clinical uses are allergic diseases, in combination with other immunosuppressive agents to prevent solid transplants rejection , and for treatment of different autoimmune diseases.

2-Antiproliferative drugs

affect the cell division of actively dividing cells including immune cells and cancer cells. used for cancer chemotherapy, useful as immunosuppressive agents. The major side effects of these agents are myelo-suppression .
4. Methotrexate
It is a folic acid antagonist and blocks both DNA and RNA synthesis. It is commonly used in the treatment of rheumatoid arthritis
3. Cyclophosphamid
It is an alkylating agent that inhibits DNA synthesis. It is used in the treatment of many autoimmune diseases

2. Mycophenolate mofitil

which has a similar action to azathioprine but more powerful with less myelotoxicity.
1. Azathioprine
inhibits purine synthesis consequently blocking DNA It is used to prevent graft rejection and treatment of many autoimmune diseases.


Azathioprine and Mycophenolate mofitil are purine analogue
3. Calcineurine inhibitors and Proliferation signal inhibitors

A-Calcineurin inhibitor :inhibit IL-2 production that leads to inhibition of T lymphocytes activation and proliferation.
1. Cyclosporine: used to prevent graft rejection.
2. Tacrolimus: It is more potent than cyclosporine .
B-Proliferation signal inhibitors (Sirolimus) Sirolimus acts on T-cells at the level of post-activation and it is not nephrotoxic.

4-Biological agents

These agents mainly polyclonal or monoclonal antibodies target antigens on the lymphocytes or cytokines and cytokine receptors.

1. Polyclonal antibodies: Antithymocyte globulin (ATG) can deplete the long-lived peripheral T lymphocytes. It is used in the treatment of
acute rejection episodes
GvHD in combination with other immunosuppressive agents
treatment of aplastic anaemia.

The main side effects are serum sickness-like reaction.

2. Chimeric/ monoclonal antibodies .

Immunotherapy

1. Induction the formation of IgG blocking antibodies can catch the allergens before reaching the basophiles/mast cells.
2. Induction of some changes in the T-cell regulatory mechanism
3. Induction of tolerance

The immunotherapy is done by Subcutaneous injections of the sensitizing allergen

Indications for immunotherapy
1. Severe allergic rhinitis
2. Allergic asthma not responding to drug therapy
3. IgE-mediated allergy to drugs
4. Anaphylaxis to insect venom