While the production of antibody through the humoral immune response can effectively lead to the elimination of a variety of pathogens, bacteria that have evolved to invade and multiply within phagocytic cells of the immune response pose a different threat. The following graphics illustrate this dilemma:
|Non-encapsulated microorganisms are easily phagocytosed and killed within macrophages.|
|Encapsulated microorganisms require the production of antibody in order to be effectively
phagocytosed. Once engulfed, however, they are easily killed.
|Intracellular microorganisms elicit the production of antibody, which allows effective phagocytosis. Once engulfed, however, they survive within the phagocyte and eventually kill it.|
|Intracellular microorganisms also activate specific T-cells, which then release lymphokines (e.g. IFN, TNF) that cause macrophage activation. Activated ("killer") macrophages are then very effective at destroying the intracellular pathogens.|
The second half of the cell-mediated immune response is involved in rejection of foreign grafts and the elimination of
tumors and virus-infected cells. The effector cells involved in these processes are cytotoxic T-lymphocytes (CTLs),
NK-cells and K-cells. Each of these effector cells recognizes their target by different means, described below.
CTLs, like other T-cells are both antigen and MHC-restricted. That is, CTLs require i) recognition of a specific antigenic determinant and ii) recognition of "self" MHC (Click here to review these requirements). Briefly, CTLs recognize antigen via their T-cell receptor. This receptor makes specific contacts with the antigenic determinant and the target cell's class I MHC molecule. CTLs also express CD8, which may assist the antigen recognition process. Once recognition is successful, the CTL "programs" the target cell for self-destruction. This process is thought to occur in one of several possible ways. First, CTLs may release a substance known as perforin in the space between the CTL and its target. In the presence of calcium ions, the perforin polymerizes, forming channels in the target cell's membrane. These channels may cause the target cell to lyse. Second, the CTL may also release various enzymes that pass through the polyperforin channels, causing target cell damage. Third, the CTL may release lymphokines and/or cytokines that interact with specific receptors on the target cell surface, causing internal responses that lead to destruction of the target cell. CTLs principally act to eliminate endogenous antigens. Click here for more information.