Adaptive immunity develops when innate immunity is ineffective in eliminating infectious agents and the infection is established. The primary functions of the adaptive immune response are the recognition of specific “non-self” antigens in the presence of “self” antigens; the generation of pathogen-specific immunologic effector pathways that eliminate specific pathogens or pathogen-infected cells; and the development of an immunologic memory that can quickly eliminate a specific pathogen should subsequent infections occur. The cells of the adaptive immune system include: T cells, which are activated through the action of antigen presenting cells (APCs), and B cells.
T cells derive from hematopoietic stem cells in bone marrow and, following migration, mature in the thymus. These cells express a unique antigen-binding receptor on their membrane, known as the T-cell receptor (TCR), and as previously mentioned, require the action of APCs (usually dendritic cells, but also macrophages, B cells, fibroblasts and epithelial cells) to recognize a specific antigen.
The surfaces of APCs express cell-surface proteins known as the major histocompatibility complex (MHC). MHC are classified as either class I (also termed human leukocyte antigen [HLA] A, B and C) which are found on all nucleated cells, or class II (also termed HLA, DP, DQ and DR) which are found on only certain cells of the immune system, including macrophages, dendritic cells and B cells. Class I MHC molecules present endogenous (intracellular) peptides while class II molecules present exogenous (extracellular) peptides. The MHC protein displays fragments of antigens (peptides) when a cell is infected with a pathogen or has phagocytosed foreign proteins.
T cells are activated when they encounter an APC that has digested an antigen and is displaying antigen fragments bound to its MHC molecules. The MHC-antigen complex activates the TCR and the T cell secretes cytokines which further control the immune response. This antigen presentation process stimulates T cells to differentiate into either cytotoxic T cells (CD8+ cells) or T-helper (Th) cells (CD4+ cells). Cytotoxic T cells are primarily involved in the destruction of cells infected by foreign agents. They are activated by the interaction of their TCR with peptide-bound MHC class I molecules. Clonal expansion of cytotoxic T cells produce effector cells which release perforin and granzyme (proteins that causes lysis of target cells) and granulysin (a substance that induces apoptosis of target cells). Upon resolution of the infection, most effector cells die and are cleared by phagocytes. However, a few of these cells are retained as memory cells that can quickly differentiate into effector cells upon subsequent encounters with the same antigen.
T helper (Th) cells play an important role in establishing and maximizing the immune response. These cells have no cytotoxic or phagocytic activity, and cannot kill infected cells or clear pathogens. However, they “mediate” the immune response by directing other cells to perform these tasks. Th cells are activated through TCR recognition of antigen bound to class II MHC molecules. Once activated, Th cells release cytokines that influence the activity of many cell types, including the APCs that activate them.