26.4 The non-specific system responds to infection with the inflammatory response and with fever.

Figure 26.12: An inflammatory response.
Figure 26.13: A mast cell.

While we don’t notice that our non-specific immune system is constantly on patrol for invaders, we definitely do notice when it responds at the site of an infection. A little response is quickly amplified into a noticeable one. Think about what happens when you get a splinter. Initially, you might feel only the pain of the splinter going into your finger. Within minutes, though, you feel pain and warmth, and see that the area around the splinter is red and swollen. The changes you are observing at the site of the splinter are the signs of an inflammatory response. The inflammatory response is a combination of events that leads to the recruitment of phagocytes and other immune cells to assist with pathogen destruction, followed by tissue healing. Whenever tissues are damaged by an invading pathogen such as a virus infecting throat cells, or by a physical injury such as a burn, bug bite, or other wound to the skin, the inflammatory response is triggered (FIGURE 26-12).

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In the first century A.D., the Romans first described the four signs of inflammation: redness, heat, swelling, and pain—hence the term used today, “inflammation,” which means, literally, “setting on fire.” Whether it is a sore throat or wounded skin, these hallmarks of inflammation are always the same.

Let’s imagine a scenario in which you cut your finger with a small knife while slicing a bagel. Three quick steps happen within a matter of minutes. First, invading pathogens from the knife and the skin surface are quickly engulfed by the macrophages that reside outside the blood vessels, in all tissues. Second, those macrophages release cytokines to recruit more phagocytes to the wound location. And, third, the cytokines also summon two other types of white blood cells, which initiate inflammation. Basophils, which circulate in the blood, and mast cells, found in the tissues (FIGURE 26-13), both release histamine, a molecule that produces inflammation by causing nearby non-injured blood vessels to (1) dilate (open up and become wider) and (2) become leaky.

When blood vessels dilate, the flow of blood increases and allows a faster, greater supply of defensive molecules and cells that can fight infection. The increased leakiness of the blood vessels makes it easier for neutrophils to exit the blood, enter tissue at the site of infection, and begin destroying any invading pathogens. The increased blood supply at the site of injury causes the redness and heat associated with inflammation. The leakiness is the reason for the swelling, because fluid leaking from the blood vessels accumulates in the tissue. And the increased pressure stimulates local pain receptors. Macrophages and neutrophils then begin an immediate response to destroy pathogens, and they also release cytokines that call more immune cells to the infection site (FIGURE 26-14).

Figure 26.14: Reacting to injury.

Complement proteins also play a role in inflammation. Just as cytokines (secreted by macrophages) trigger the inflammatory response, activated complement proteins can also trigger initial inflammatory reactions. Activated complement proteins at the site of an infection cause mast cells to release histamine and further amplify the inflammatory response by attracting additional phagocytes. As mentioned in Section 26-3, complement proteins also directly affect pathogens by attacking their membranes and making it easier for phagocytes to engulf them.

Figure 26.15: Turning up the thermostat. Fever slows the growth of pathogens.

So what about that cut on your finger? A scab—formed from dried, clotted blood and interstitial fluid—temporarily forms to cover the wound, much like a natural Band-Aid, and prevents more pathogens from entering. At the end of the inflammatory process, collagen fibers are secreted by nearby cells to close the wound in a more stable fashion, and the scab falls off. Skin begins to grow back, once again forming an impenetrable barrier. And you are more cautious about cutting bagels!

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Sometimes an infection is overcome quickly by the inflammatory response and is confined to the site of damage. However, if pathogens are not quickly destroyed, macrophages will be constantly stimulated and will continue to release cytokines. Some cytokines can cause a fever, an elevated body temperature, if their concentration is high enough—a situation that both stimulates the immune response and reduces the rate at which many pathogenic bacteria can divide. The fever-causing cytokines travel through the bloodstream and affect a region of the brain, called the hypothalamus, that functions as the body’s thermostat (see Section 23-17). Just as you can change the settings on your home thermostat, your body’s thermostat can also be set higher, thus leading to a fever (FIGURE 26-15).

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When your body’s thermostat is set higher with a fever, you feel cold and your body responds with rapid periods of muscle contractions and relaxations (shivers and chills). Chills are the body’s way of trying to warm up to the higher temperature setting of the thermostat. When your fever “breaks,” the thermostat is being reset to normal. You sweat because your body is now too hot, and sweating cools your body down. Anti-inflammatory medicines such as aspirin, acetaminophen, and ibuprofen help to lower a fever by blocking steps in the biochemical pathways promoted by the fever-producing cytokines. A very high fever (105° F or higher) is extremely dangerous and can be fatal. At such high temperatures, proteins can denature (unfold) and critical biochemical processes can malfunction, causing cellular stress and, in small children, seizures.

Q

Question 26.4

Why do chills and sweating sometimes occur together when you have a fever?

In the StreetBio at the end of Chapter 20, we described “Darwinian medicine,” a new perspective on when to treat and when not to treat symptoms. From this perspective, many protective responses that have evolved in organisms are recognized as having value in fighting illness. And consequently, treating symptoms such as fever, which is actually part of the immune system response to infection, can hinder our efforts at fighting infection. This idea was supported, for example, by the observation that chicken pox lasted longer, on average, in patients taking aspirin than in patients taking a non-fever-reducing placebo.

Q

Question 26.5

Is it always wise to treat a fever with aspirin or other medication?

TAKE-HOME MESSAGE 26.4

Inflammation is a major way in which pathogens are eliminated by the non-specific immune system. The four recognizable signs of the inflammatory response (redness, heat, swelling, and pain) are related to the changes in blood vessels that enhance the recruitment of phagocytes and complement proteins to the site of inflammation. Fever-promoting cytokines help the body fight infection by stimulating immune responses and inhibiting the growth of some pathogens.

Describe the events (beginning with a wound) that cause the signs of inflammation.

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