Although the immune system is essential for protection against pathogens, in certain instances its powerful destructive mechanisms do more harm than good. Examples include hypersensitivity reactions, autoimmune disorders, and rejection reactions to transplanted tissues. Drugs that suppress immune mechanisms play an important role in treating these conditions. Increasingly, monoclonal antibodies targeting proteins with key roles in immune responses are being developed as immunosuppressive agents. In some situations, drugs that potentiate the immune response provide benefit.
|Antigen-presenting cells (APCs)||Dendritic and Langerhans cells, macrophages, and B lymphocytes involved in the processing of proteins into cell surface forms recognizable by lymphoid cells|
|B cells||Lymphoid cells derived from the bone marrow that mediate humoral immunity through the formation of antibodies|
|Clusters of differentiation (CDs)||Specific cell surface constituents identified by number (eg, CD4, CD8)|
|Cytokines||Polypeptide modulators of cellular functions, including interferons, interleukins, and growth-stimulating factors|
|Immunophilins||A family of cytoplasmic proteins that bind to the immunosuppressants cyclosporine, tacrolimus, and sirolimus and assist these drugs in inhibiting T- and B-cell function|
|Major histocompatibility complex (MHC)||Cell surface molecules that bind antigen fragments and, when bound to antigen fragments, are recognized by helper T cells. MHC class I molecules are expressed by all cells, whereas MHC class II molecules are expressed by antigen-presenting cells|
|Monoclonal antibody (MAb)||An antibody produced by a hybridoma clone that selectively binds to an antigen of biological or medical interest.|
|T cells||Lymphoid cells derived from the thymus that mediate cellular immunity and can modify humoral immunity. The main subclasses of T cells are CD4 (helper) cells and CD8 (cytotoxic) cells|
Using the concerted actions of complement components, phagocytic cells, and natural killer (NK) cells, the innate immune system initiates the defense against pathogens and antigenic insult. If the innate response is inadequate, the adaptive immune response is mobilized. This culminates in activation of T lymphocytes, the effectors of cell-mediated immunity, and production of antibodies by activated B lymphocytes, the effectors of humoral immunity. The subsets of lymphocytes that mediate different parts of the immune response can be identified by specific cell surface components or clusters of differentiation (CDs). For example, helper T (TH) cells bear the CD4 protein complex, whereas cytotoxic T lymphocytes express the CD8 protein complex.
Antigen Recognition and Processing
This critical inaugural step in the adaptive immune response involves antigen-presenting cells (APCs), which process antigens into small peptides recognized by T-cell receptors (TCRs) on the surface of CD4 TH cells (Figure 55–1). The most important antigen-presenting cell surface molecules are the major histocompatibility complex (MHC) class I and II proteins. The activation of TH cells by the class II MHC-peptide complex requires participation of costimulatory and adhesion molecules in addition to activation of T-cell receptors.