26.10 Cytotoxic T cells and helper T cells serve different functions.

The specific immune response, as we saw in Section 26-7, has two parts: the humoral response (B cells) and the cell-mediated response (T cells). While antibodies operate in the realm of the blood and lymph, it is the role of the T cell-mediated response to fight pathogens that are already inside cells. We focus here on this T cell-mediated response, and begin by examining the two major types of T cells, both of which are lymphocytes.

1. Cytotoxic T cells are the effectors (the first responders) of the cell-mediated response; they directly kill cells infected with pathogens.

2. Helper T cells do not directly kill infected cells, but, instead, stimulate other immune cells. Helper T cells stimulate B cells to produce antibodies and cytotoxic T cells to kill infected cells.

We’ll follow a viral infection through the cell-mediated response to demonstrate one example of how T cells function (FIGURE 26-26).

When a pathogen enters the body, the phagocytes and NK cells of the non-specific system respond. At the same time, dendritic cells and macrophages call on the specific system by “advertising” the presence of antigens to circulating lymphocytes. Dendritic cells and macrophages (as well as B cells) that “present” digested particles of pathogens on their cell surfaces as a means of advertising are called antigen-presenting cells. Presenting cells are essential to all T cell functioning, because T cells can recognize infected cells only by the “non-self” antigens presented on their plasma membranes.

Circulating through a lymph node or the spleen, a macrophage may bump into helper T cells with specificity for the viral antigen being presented on the macrophage surface. The helper T cell receptor recognizes the antigen, and the T cell locks onto the antigen-presenting macrophage. Once this binding has taken place, the helper T cell has been activated. Activated helper T cells quickly ramp up an immune response by producing signaling molecules (cytokines) that activate the other type of T cell, the cytotoxic T cells. This is important because cytotoxic T cells are the only T cells that kill infected cells.

Both helper T cells and cytotoxic T cells then undergo clonal expansion, producing vast numbers of memory and effector cells with specificity for the viral antigen. Other cytokines produced by the activated helper T cells provide the final signals that make the cytotoxic T cells “mature” and ready to fight the pathogen at the site of infection. You may notice this process occurring when you’ve been sick: the rapid division of lymphocytes in the lymph nodes causes the nodes to swell (usually called “swollen glands”). The helper T cells and cytotoxic T cells then leave the lymph nodes or spleen and circulate throughout the body. (Helper T cells also are required to stimulate B cells to produce antibodies; B cell development occurs only in response to these signals from helper T cells.)

Mature cytotoxic effector cells are like newly trained soldiers, ready to fight the enemy, but first they need to detect where the enemy is hiding. Consider a cell in the throat that is infected with a respiratory virus. Is the cell revealing that it’s under attack? Yes! The infected cell displays some of the pathogen’s molecules on its surface receptors, advertising the infection to the now numerous cytotoxic T cells that can recognize that specific respiratory virus.

How do the cytotoxic effector cells fight the internal pathogen? They do something drastic—they kill the cell that is infected. The weapons that they use are proteins: some punch holes in the cell’s plasma membrane, and others promote the cell’s self-destruction, or apoptosis. This programmed cell death does not explode the cell—sending virus particles everywhere. Just the opposite: it is a neatly organized, well-orchestrated process carried out by enzymes that break down macromolecules inside the cell (including the pathogen), fragment the cell into smaller pieces, and package the pieces in vesicles (FIGURE 26-27). The vesicles are then engulfed and digested by phagocytes. So, while some body cells are lost in the battle, ultimately it is for the good of the entire organism.

Because memory helper T cells and memory cytotoxic T cells are also made during an infection, this same virus cannot cause illness again. Memory cells will leap into action to make more effector cells if the virus ever returns.