The membranes of a number of cells, including NK cells, macrophages, neutrophils, and eosinophils, possess immunoglobulin Fc receptors and can kill certain target cells. NK cells recognize the Fc region of antibodies and preferentially attack and destroy target cells, usually those coated with IgG antibodies (Fig. 14.7). The recognition and subsequent destruction of antibody-coated target cells by NK cells is called antibody-dependent cell-mediated cytotoxicity (ADCC). The antibodies in ADCC that coat the target cells often include tumor-specifc antibodies. This binding (through the Fc region) results in the apoptosis and lysis of the target cell.
If the antigen is a bacterium, the antigen–antibody complex may also activate a system of plasma proteins called the complement system and cause one of its components, usually C3, to bind to the bacterium and act as a ligand for its phagocytosis by macrophages. Complement-bound foreign cells are also targets of ADCC.
The cell-mediated immune response: Cytotoxic CD8 T lymphocytes (CTLs) target and destroy transformed and virus-infected cells.
When the TCR of a CTL recognizes and binds to an anti-gen–MHC I complex on the surface of a transformed or virusinfected cell, the activation process is triggered. First, CTLs undergo “clonal expansion” by entering the cell cycle and proceeding with cell divisions followed by differentiation into effector (“killer”) cells. During differentiation, a large number of secretory vesicles are formed containing specific proteins that include perforins and granzymes (fragmentins). As a result of interaction with antigen, CTLs secrete these proteins. Perforins are pore-forming proteins that enter the target cell by forming ringlike transmembrane channels in their cell membranes. These channels cause an increase in the permeability of the membrane that contributes to cell death. Granzymes are exogenous serine proteinases that are released from cytoplasmic granules and pass into the target cells through the pores created by perforins. Once inside the cell, granzymes activate caspases that induce the cell to undergo apoptosis (Fig. 14.8). After killing the target cell, the majority of activated CTLs will die (of apoptosis), but some of them that interacted with helper T cells will become memory cells.
CD4CD25FOXP3 suppressor T lymphocytes suppress the immune responses of other lymphocytes.
Once the immune reactions are initiated by contact with antigen, the immune system is capable of controlling the
FIGURE 14.8 • Schematic diagram of T-cell activation leading to elimination of a virus-infected host cell. The TCR–CD3 complex on a helper CD4 T lymphocyte recognizes foreign antigen displayed on an MHC II molecule on the surface of a macrophage. This recognition triggers a rapid response from B lymphocytes and the release of interleukin 2 (IL-2). The same macrophage also expresses MHC I molecules (like every other cell in the body) that interact with the appropriate TCR on the surface of a cytotoxic CD8 T lymphocyte. The cytotoxic CD8 T lymphocyte also possesses IL-2 receptors. IL-2 binding to these receptors stimulates the cell to divide and differentiate. The newly formed cytotoxic CD8 T lymphocytes migrate to the site of viral infection. There the TCRs recognize the viral antigens displayed on the surface of MHC I molecules of infected cells. After successfully recognizing these “nonself” proteins, the cytotoxic CD8 T lymphocytes secrete perforins and granzymes, killing the infected cells.