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Immunopathologic Mechanisms: Introduction |  |
| The primary role of the immune system is the discrimination of self and non-self. The fundamental purpose of recognition of non-self is to protect against invading microorganisms, chemical agents, or other foreign substances. To eliminate non-self agents, the immune system has developed a variety of mechanisms, including inactivation of biologic agents, lysis of foreign cells, agglutination or precipitation of molecules or cells, or phagocytosis of foreign materials. Generating the
right class of immune response is under the control of dendritic cells (DC). DC can be considered immunologic sensors—they are scattered throughout the body, sense environmental stimuli, and convey this information to naïve lymphocytes to tune the relevant immune response. For example, in response to intracellular microbes such as viruses or certain bacteria, DC secrete interleukin-12 (IL12), inducing T-helper cells (TH) to
differentiate into TH1. TH1 cells promote cell-mediated immunity through production of γ-interferon (IFNγ) and IL2. In contrast, extracellular pathogens such as helminths lead DC to secrete IL4 and to trigger the naïve TH cells toward TH 2 differentiation. TH2 cells promote antibody production through the secretion of
IL4, IL5, IL10, and IL13, which increase IgE production, eosinophils and mast cells. The protective immune response against a non-self agent is a complex program including the nature of the stimuli, DC subsets, TH subsets, and polarized cytokine profiles. |
| However, under certain circumstances, these normally protective responses can result in significant tissue damage; these immunopathologic mechanisms are called immune-mediated diseases. There are 4 general classical classifications of these diseases, which are mediated either through antibodies (Types I, II, and III) or by cells (Type IV). Many theories exist to explain immune-mediated diseases including external environmental factors, genetic predisposition, and hormonal
influences. Recently immune-mediated diseases have been categorized in light of TH1 and TH 2 polarization. TH1 cells are associated with autoimmune diseases (Type II) and TH 2 cells with allergic diseases, immune complex disorders, and delayed-type hypersensitivity (Types I, III, and IV). |
| Corticosteroids, with or without other immunosuppressive drugs, are currently the mainstay of immune-mediated disease treatment. The primary challenge in this area is to find specific agents that precisely correct the dysregulation of TH1/TH 2 homeostasis. |
