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| The Central Role of Helper T Cells |
Helper T (TH) cells are critical to coordinating the activity of the immune response. The chemical messages they secrete (cytokines) stimulate the non-specific immune response to continue, and strengthen and boost appropriate specific responses. Helper T cells have sometimes been called the "conductors" of the immune system because they coordinate activity like the conductor of a symphony. They have also been called the "generals" of the immune system because they call up troops of B cells, cytotoxic T cells, and other helper T cells to go into battle against invading pathogens (Fig. 1).
Macrophages alert helper T cells to the presence of pathogens. These phagocytic macrophages engulf bacteria and viruses, and can display foreign antigens - the identifying proteins of the bacteria or viruses - on the surface of their cell membrane. Embedded within the macrophage cell membrane is a molecule produced by the human leukocyte antigen (HLA) complex. (See the Human Evolution unit.) The helper T cells bind simultaneously to the foreign antigen and the HLA molecule. Only TH cells with receptors that match those of the foreign antigen on the activated macrophage are able to bind and respond to the call to action. Once bound, the helper T cell proliferates to form a clone of cells, each capable of recognizing the same antigen. The members of the helper T clone, the generals, generate the chemical signals that call up the troops.
Some signals sent by helper T cells stimulate cytotoxic T cells (TC). Cytotoxic T cells (also known as killer T cells) bind cells that have been altered, such as by viral infection; they avoid healthy cells. Surface antigens on the altered cell perform the binding. These antigens are specific to the offending agent, and match receptors in the membrane of the specific TC cell. In addition, the TC cell simultaneously binds an MHC molecule on the surface of the infected cell. Once bound by both the foreign antigen and the HLA molecule, the cytotoxic T cell secretes a chemical called "perforin," which destroys the offending cell (Fig. 2).
Helper T cells also stimulate the production of antibodies. Chemical signals from helper T cells stimulate the production of B cells specific to an infecting pathogen, and then stimulate the B cells to differentiate into plasma cells. The plasma cells are factories for the production of antibodies, which are specific to given pathogens circulating in blood or lymph. Antibodies work by blocking the receptors that allow pathogens to attach to target cells, or by creating clumps of bacteria. Clumping makes the job of phagocytes easier, as they will more readily engulf bacteria in clumps. Bound antibodies sometimes serve as tags, called opsonins, enhancing phagocytosis. Antibody binding can also initiate a cascade of biochemical reactions, activating a set of chemicals known as complement. Activated complement components can form holes in bacterial membranes and enhance inflammation.
Helper T cells are clearly critical to the operation of the immune system. If they are destroyed because of an HIV infection, the whole system is crippled. The immune system is described as having two "arms": the cellular arm, which depends on T cells to mediate attacks on virally infected or cancerous cells; and the humoral arm, which depends on antibodies to clear antigens circulating in blood and lymph. As an HIV infection progresses, destroying helper T cells, both arms of immunity are impaired.