26.3 The non-specific division of the immune system recognizes and fights pathogens and signals for additional defenses.

Sometimes security measures fail. When intruders break through a defensive wall, the building’s security guards need to (1) locate the security breach, (2) call for backup, and (3) attack and remove as many of the invaders as possible. Similarly, your body recognizes any security breaches, such as a wound to the skin or some spoiled food you’ve eaten, and then responds instantly to prevent an infection (FIGURE 26-8). Chemical signals are put out to call for backup cells, and cellular and molecular weapons are used to destroy both the pathogens and any cells they’ve infected.

In this section, we examine the cells that perform these duties and the tools that they use to combat infection. White blood cells (introduced in Section 21-8) are specialized cells that play roles in specific and non-specific immunity, but we focus here on non-specific immunity. These cells are made in the bone marrow and released into the bloodstream, where they patrol the body’s tissues and search for invaders.

Patrolling white blood cells are able to distinguish the body’s own cells (“self”) from invaders (“non-self”) because of unique molecules found on the surface of pathogens. The immune cell surface receptors recognize these distinctive molecules, usually proteins, and bind to them. Because your own cells do not contain these molecules, a cell that possesses any of them can be identified as an invader (non-self) by the cells of the non-specific part of the immune system.

This type of recognition is considered non-specific because immune cell receptors recognize and bind to classes of molecules shared by a wide array of organisms. For example, one receptor recognizes a protein contained in all bacterial flagella. Another receptor recognizes a molecule found in the cell walls of many types of fungi.

Once the immune system cells recognize these molecules and bind to them, the cells of the non-specific immune system begin to attack. There are four types of white blood cells that mount the non-specific defense (FIGURE 26-9).

1. Neutrophils circulate in the blood and exit blood vessels at sites of injury and infection in tissues. These cells are phagocytes, ingesting harmful particles or pathogens, primarily bacteria. Neutrophils normally make up between 50% and 70% of all white blood cells circulating in the bloodstream, and their numbers increase dramatically and rapidly during the first few days of some infections. Neutrophils destroy themselves as they ingest pathogens and live only 3–5 days, on average.

After self-destruction, the dead neutrophils become a major part of pus, the thick yellowish fluid we often notice at the site of infection. (Other components of pus include damaged cell debris from the invaded tissue and both live and dead pathogens.) Often, our bodies can clear infections on their own or with some help from an antiseptic, a solution used on a body surface to kill or discourage growth of microorganisms, such as rubbing alcohol or hydrogen peroxide. But when there is excessive pus, combined with signs of a more serious infection, antibiotics might be needed to kill bacteria inside the body.

2. Macrophages are large (“macro”) phagocytic white blood cells that reside in and patrol the tissues (outside the blood vessels). They engulf and digest small pathogens whole. Macrophages also remove any pathogen and neutrophil debris that remains after the neutrophils have done their job. Unlike neutrophils, however, macrophages do not destroy themselves. Once macrophages have ingested a pathogen, they “present” digested pieces of the pathogen on their cell surface, “advertising” the infection to cells of the specific system. We’ll learn more about the role of these “presenting cells” when we examine specific immunity (see Section 26-10).

Neutrophils and macrophages employ chemical warfare to destroy pathogens. For example, both types of cells can produce hydrogen peroxide and hypochlorous acid (also components of household bleach), two chemicals that are effective in killing bacteria and fungi.

3. Dendritic cells are phagocytes that link the non-specific and specific divisions of the immune system by “presenting” the cells of the specific system with foreign matter. Present in skin and mucous membranes, such as those lining the nose, lungs, stomach, and intestines, these phagocytic cells, once activated, migrate to the lymph nodes, where they interact with cells of the specific immune system.

4. Natural killer (NK) cells are the first line of resistance to viruses. They kill viruses, not by ingesting the virus by phagocytosis, but by killing a virus-infected cell by poking holes in it, thereby killing both the virus and the cell. The initial response of the NK cells may eliminate a viral infection, or at least slow it down until the specific system can respond to the virus in a more specific manner. NK cells also play a role in recognizing and killing cancer cells (FIGURE 26-10).

Although the cells of the non-specific system are the initial responders to a pathogen, there are never enough of them at the initial site of infection to ingest and kill all the invading pathogens. Thus, after recognizing the security breach and starting the response, the patrolling cells of the non-specific system sound the alarm and call for backup.

Additional support for the non-specific immune response is provided by several types of proteins. The chief way that cells of the immune system—both the specific and non-specific divisions—talk to one another is by secreting signaling proteins called cytokines in response to pathogens in the body. Cytokines secreted by one immune cell can bind to receptors on other immune cells and signal them to respond in various ways. For example, cytokine binding can cause immune cells to move closer to the site where the cytokines are being produced (cyto = cell; kine = to move).

Interferons are an important type of cytokine produced by cells infected by a virus. An interferon alerts nearby healthy cells to turn on protective measures that help them resist viruses. These alerted cells take on an “antiviral state” in which they transcribe specific genes and translate them into proteins that can inhibit viral replication and can degrade viral RNA.

In addition to using the cells we’ve learned about here, the non-specific system can also make use of some circulating defensive proteins, collectively called complement proteins, to quickly recognize and destroy invaders. These proteins “complement” (work with) the activities of cells in the non-specific and specific immune systems and can link the two systems. Foreign molecules, such as the components of bacterial cell walls, activate the complement proteins (FIGURE 26-11). Once activated, the complement proteins fight pathogens in several ways. For example, a particular combination of complement proteins can blast holes in the cell membranes of pathogenic organisms, allowing water and ions, but not larger molecules such as proteins, to pass through. As a result, water rushes inward and the pathogen swells and bursts. Other complement proteins help destroy pathogens by sticking to them and forming a coating that enhances the ability of phagocytes to bind and engulf them.