Alert! Some bacteria have penetrated your skin and have taken up residence in an underlying tissue. They're beginning to feed off the goodies in your body fluids and, since they divide hourly, will soon pose a threat if their presence goes unchecked. Embedded in the attacked tissue are macrophages which, using the receptors described previously, have detected the invaders. Their response is complex. They begin by changing their nature. The receptors on their surface have signaled to the nucleus to begin to synthesize proteins that cause the cell to grow, produce poisons that kill bacteria, secrete cytokines, and increase their ability to phagocytose microbes. Your immune system has begun to fight.
Here are some of things I've learned about phagocytosis. After detecting the invader, the macrophage surrounds it with its membrane much like an amoeba engulfing its prey. The membrane pinches off, forming a vesicle, a membrane bound vessel that encloses the bacterium. This body then fuses with another membrane bound structure (a "lysosome", if you must know) that is already present in the cell. These vesicles contain more than 60 different enzymes, acids, and noxious chemicals that act in concert to kill and digest the bacterium. The cartoon at the right copied from the Wikipedia entry on "phagocytosis" may help to illustrate the phenomenon. Lots more is known about the process but I decided that that's all I needed to know for now.
While all this destruction is going on, the macrophage sends for additional help. It secretes cytokines, mentioned above and in the last post, small proteins that act as signals to other cells. Another group of white blood cells circulating in the blood, monocytes, respond and, upon exit from blood vessels, turn into additional macrophages. Other cytokines released from alerted macrophages interact with the walls of surrounding blood vessels increasing their flow to the affected tissues. The blood vessels also contact, releasing fluid, causing swelling. The upshot of all this is the inflammatory response that we experience upon infection.
Macrophage cells are excellent sentinels and reasonably good phagocytes. But the premier phagocytic cells are waiting in the wings to respond if the intrusion of foreign microbes is more serious than the macrophages can handle. It is the neutrophils, the innate systems' heavy infantry that bring big artillery to the fight. Unlike macrophages, which are resident in solid tissues, neutrophils reside in the blood. In fact, they make up about half of all the white blood cells in circulation. That comes to 20 billion cells in case you're counting. They're more plentiful and more powerful than macrophages, capable of not only phagocytosis, but the secretion of a host of destruction chemicals into their surroundings. They're highly motile and quickly move to the sites where they're needed, hungrily feeding on invaders and throwing chemical bombs when they reach their destination. But they're short lived, with a lifespan shorter than macrophages, carrying out their functions and then dying. What we call "pus" are the remnants of neutrophils who have accomplished their mission.
Besides phagocytosis and chemical warfare, there's another way that neutrophils kill, a way that was a complete shock to me. For many years I had been telling numerous classes that DNA doesn't do anything. I explained that DNA acts as a set of instructions, as a foreman or boss, directing others, never actually getting its hands dirty. But now I find out that neutrophils make use of DNA to form physical traps. They release a complex mixture of DNA and enzymes into a site of bacterial invasion that immobilizes pathogens, preventing them from moving, and killing them with a mixture of various proteins.
After reading about how neutrophils perform their function, I had two questions. First, how do circulating neutrophils know where to go? And second, what prevents neutrophils from running amok? They're certainly powerful warriors but after the fight is over, how do you stop the destruction? I'll tackle both questions in the next post.