Chapter 46 Immunopharmacology

Immunology is the study of how normal body defenses resist and overcome invasion from infectious organisms Immunosuppression refers to actions or drugs that decrease immune activity Used after organ transplantation and in treatment of severe inflammatory and allergic conditions Immunomodulation refers to actions or drugs that stimulate the activity of the immune system Used for treatment of various cancers, hepatitis, and myelosuppression Immune System Learning Outcome 46.1 Describe the immune response and how the different immune cells work together to protect the body. The immune system is made up of lymphoid tissues (bone marrow, tonsils, lymph nodes, spleen) and cells (macrophages, lymphocytes) that are found in the blood and most body organs. Lymphocytes are divided into T-cells, which mature in the thymus gland, and B-cells, which originate in the bone marrow. These cells multiply and help protect the body when the immune system is activated. Lymphocytes and macrophages also produce chemical mediators, called cytokines, that help regulate the activity of the immune system. Cytokines are classified into the interleukins and the interferons. These mediators act as chemical messengers that regulate and direct the activity of the various immune cells.

Immune System Cells involved in the immune response Macrophages - Phagocytize infectious organisms and foreign substances Referred to as antigen-presenting cells (APCs) that recognize and display foreign antigens to other immune cells Helper T-cells Multiply and increase in numbers Activate killer T-cells and B-cells Killer T-cells - Cytotoxic lymphocytes Attack and kill cells that are infected with foreign organisms B-cells Function as APCs and produce antibodies Antibodies inactivate antigens located on infectious organisms and foreign substances Learning Outcome 46.1 Describe the immune response and how the different immune cells work together to protect the body. Macrophages are scavenger cells that phagocytize infectious organisms and foreign substances. Antigen-presenting cells (APCs) are immune cells that recognize foreign antigens. After recognition and processing of a foreign antigen, the APCs display the antigen to other immune cells, especially helper T-cells. The function of helper T-cells is to recognize the foreign antigens presented to them by macrophages and other APCs. Helper T-cells then release interleukins and other chemical factors that activate killer T-cells (cytotoxic T-cells) and B-cells to multiply and increase in numbers.

Immuno-suppressive Drugs Useful in the treatment of: Severe allergic reactions Immune-based diseases Prevent organ rejection after transplantation Corticosteroid drugs Reduces the number of circulating lymphocytes in the blood Also inhibit synthesis of inflammatory mediators such as prostaglandins which is what accounts for most of the immunosuppressant action Patients on immunosuppressant drugs should be monitored for signs of infection They should report chills, fever, sore throat, swollen glands, tiredness, or any other symptoms that could indicate infection Learning Outcome 46.2 Identify the mechanism of action and uses of the cytotoxic, noncytotoxic, and monoclonal antibodies indicated for immunosuppression. Drugs that have the ability to suppress the immune response are useful in the treatment of severe allergic reactions and immune-based diseases such as multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. These drugs are also essential in preventing organ rejection following organ transplantation. In these conditions, inappropriate activation of the immune system causes inflammatory reactions that lead to destruction of body tissue and rejection of transplanted organs. Corticosteroids produce potent anti-inflammatory and antiallergic effects. These drugs also have the ability to suppress the immune response. Prednisone (Sterapred, Sterapred DS) and methylprednisolone (Medrol) are corticosteroid drugs that are widely used. One of the main immunosuppressive effects of the corticosteroids is to cause lymphocytes in the blood to be redistributed into the bone marrow. This immunosuppressive effect (lymphopenia) occurs 4 to 6 hours following drug administration and significantly reduces the number of circulating lymphocytes in the blood.

Immunomodulating Drugs Increase the activity of the immune system Desirable in the treatment of conditions where immunological deficiencies exist Interferons Chemical mediators involved in the immune attack Immunomodulating Drugs Learning Outcome 46.3 Identify the mechanism of action and uses of the interferons, interleukins, and colony stimulating factors involved in immunomodulation. Immunomodulating drugs are those that increase the activity of the immune system and are desirable in the treatment of cancer, AIDS, and other conditions where immunological deficiencies exist. Interferons are naturally occurring proteins produced by lymphocytes and other cells of the immune system. The interferons are chemical mediators involved in the immune attack on infectious organisms and other foreign substances.

Immuno-modulating Drugs Drugs that increase the activity of the immune system are used in the treatment of cancer, AIDS, and other conditions where immunological deficiencies exist Includes interferons, Interleukin-2, and colony stimulating factors Adverse effects of these drugs include flu-like symptoms such as fever, chills, muscle aches, and bone pain Immuno-modulating Drugs Learning Outcome 46.3 Identify the mechanism of action and uses of the interferons, interleukins, and colony stimulating factors involved in immunomodulation. The three types of interferons are classified as alpha, beta, and gamma interferons. Administration is by SC or IM injection. Common adverse effects are flu-like symptoms: chills, fever, muscle aches, and pains. Interleukin-2 (IL-2) is one of the chemical mediators known as a lymphokine. It is produced by lymphocytes and other cells. Interleukin-2 is especially important for the activity of helper T-cells. It functions to stimulate B-cell production of antibodies and killer T-cell activity. These actions increase the function and response of the immune system. Fever, flu-like symptoms, and fluid retention are common adverse effects. Colony stimulating factors (CSF) are synthetic preparations of naturally occurring proteins that stimulate the formation of macrophages and granulocytes. The CSFs stimulate the bone marrow to increase the production of these blood cells. The CSFs are used to speed the recovery in patients with myelosuppression who are undergoing cancer chemotherapy or bone marrow transplantation. Common adverse effects include fever, chills, GI disturbances, and muscle and bone pain.