Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immuno-suppressive therapy to:
Types of Immunity
Immunity owing to exposure to an antigen or to the passive injection of immunoglobulins.
Immunity resulting from the development within the body of antibodies or sensitized T lymphocytes that neutralize or destroy the infective agent. This may result from the immune response to an invading organism or from inoculation with a vaccine containing a foreign antigen.
The component of immunity that is pathogen-specific and creates memory. It consists of the mechanisms of cell-mediated and antibody-mediated immunity.
Abbreviation: CMI. The regulatory and cytotoxic activities of T cells during the specific immune response. This process requires about 36 hr to reach its full effect. Synonym: T-cell–mediated immunity
Unlike B cells, T cells cannot recognize foreign antigens on their own. Foreign antigens are recognized by antigen-presenting cells (APCs) such as macrophages, which engulf them and display part of the antigens on the APC's surface next to a histocompatibility or “self-” antigen (macrophage processing). The presence of these two markers, plus the cytokine interleukin-1 (IL-1) secreted by the APCs activates CD4 helper T cells (TH cells), which regulate the activities of other cells involved in the immune response.
CMI includes direct lysis of target cells by cytotoxic T cells, creation of memory cells that trigger a rapid response when a foreign antigen is encountered for the second time, and delayed hypersensitivity to tissue and organ transplants. T cells also stimulate the activity of macrophages, B cells, and natural killer cells. These functions are controlled largely by the secretion of lymphokines such as the interleukins, interferons, and colony-stimulating factors. Lymphokines facilitate communication and proliferation of the cells in the immune system.
T-cell–mediated immune functions requiring cell interactions, e.g., graft rejection or destruction of infected cells.
Vaccination of all the household contacts of an infant against those infectious diseases that he or she might contract. It is designed to protect disease-naive newborns from potentially fatal contagious illnesses. Synonym: cocoon strategy.
Immunity present at birth. It may be natural or acquired, the latter depending on antibodies received from the mother's blood.
The ability of a community to resist epidemic disease. Herd immunity may develop naturally in a society as a result of widespread exposure to disease, or it may be stimulated artificially by mass vaccination programs.
The protective activities of antibodies against infection or reinfection by common organisms, e.g., streptococci and staphylococci. B lymphocytes with receptors to a specific antigen react when they encounter that antigen by producing plasma cells (which produce antigen-specific antibodies) and memory cells (which enable the body to produce these antibodies quickly in the event that the same antigen appears later). B-cell differentiation also is stimulated by interleukin-2 (IL-2) secreted by CD4+ T cells and foreign antigens processed by macrophages.
Antibodies produced by plasma B cells, found mainly in the blood, spleen, and lymph nodes, neutralize or destroy antigens in several ways. They kill organisms by activating the complement system; neutralize viruses and toxins released by bacteria; coat the antigen (opsonization) or form an antigen-antibody complex to stimulate phagocytosis; promote antigen clumping (agglutination); and prevent the antigen from adhering to host cells.
Those immune defenses against infection and cancer that are not determined by the specific responses of B or T lymphocytes. Innate immunity is not pathogen-specific and does not create immunological memory. It includes the actions of adhesion molecules; cellular chemotaxis; the secretion of cytokines; cytotoxicity; the activities of dendritic and natural killer cells; inflammation; and phagocytosis. Synonym: innate immune system
Immunity limited to a given area or tissue of the body.
Immunity that is genetically determined in specific species, populations, or families. Some pathogens cannot infect certain species because the cells do not provide suitable environments. For example, the measles virus cannot reproduce in canine cells and therefore dogs have natural immunity to measles.
Immunity acquired by the introduction of preformed antibodies into an unprotected individual. This can occur through intravenous infusion of immune globulin or from antibodies that pass from the mother to the fetus through the placenta in utero. Newborns also may acquire immunity through breastfeeding.
The progressive loss of protective antibodies against an antigen or disease that occurs with the passage of time. It is a crucial factor in vaccination. Booster doses of a vaccine are given when the immune response to an antigen drops below protective levels.
Immuno - Suppressive Drugs
A common side-effect of many immunosuppressive drugs is immunodeficiency, because the majority of them act non-selectively, resulting in increased susceptibility to infections and decreased cancer immunosurveillance. There are also other side-effects, such as hypertension, dyslipidemia, hyperglycemia, peptic ulcers, lipodystrophy, moon face, liver and kidney injury. The immunosuppressive drugs also interact with other medicines and affect their metabolism and action. Actual or suspected immunosuppressive agents can be evaluated in terms of their effects on lymphocyte subpopulations in tissues using immunohistochemistry.
Immunosuppressive drugs can be classified into five groups:
In pharmacologic (supraphysiologic) doses, glucocorticoids are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplant immunosuppressant to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes.
Glucocorticoids suppress the cell-mediated immunity. They act by inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, and TNF-γ, the most important of which is IL-2. Smaller cytokine production reduces the T cell proliferation.
Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts ofIL-2 and IL-2 receptors. This diminishes both B cell clone expansion and antibody synthesis.
Glucocorticoids influence all types of inflammatory events, no matter their cause. They induce the lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect.
Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines, etc.) from neutrophils, macrophages, and mastocytes.
Diagrams & Examples of
the Human Immune System
the Human Immune System
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