We will consider the non-specific fever, inflammation, and phagocytosis as the secondary line of human body defense. When microbes break through the intact primary line of defense, the body responds in an attempt to destroy or inhibit growth of microbes. In 1884, Elie Metchnikoff saw that motile cells gathered around a splinter within a mass of cells. White blood cells called phagocytes migrate into tissues (diapedesis) and move toward the site of infection (chemotaxis). Cells from the liver, spleen, bone marrow, lymph nodes, brain, and connective tissues contribute to the secondary line of defense.

Inflammation is a secondary defense response to injury, chemicals, or exposure to a living organism such as a pathogen or parasite. The blood vessels dilate leading to increased activity. Four characteristics of inflammation are redness (rubor), warmth (calor), swelling (edema or tumor), and pain (dolor). Each of the four inflammatory signs indicates that the secondary line of defense is at work. It is important that you permit your body time for these activities to occur. The redness is caused by increased blood flow to the area; the swelling indicates increased fluid to assist in washing away microbes and/or diluting toxins; and the increased body temperature inhibits sensitive microbes, increases cellular metabolism, and reduces availability of iron to the microbes. Following phagocytosis, a mixture of dead phagocytes, dead tissue cells, and dead microbes accumulates at the site of infection. This product is called pus. Sometimes the infectious microbes are confined to the site, and an abcess or boil forms. Following the defensive response, the tissue repairs and heals itself. "Squeezing" the infected area before the body defenses have completed their work may increase the chance of spreading the pathogens that are not yet dead.

Sometimes during the secondary defense against microbes, fever or increased body temperature develops. These microbes also affect the hypothalamus and stimulate an increase in body temperature. This raised body temperature increases phagocytosis and cell metabolism for tissue repair as well as inhibits the growth of some microbes.

In addition, nonspecific cells called natural killer cells (NK) circulate throughout the body and destroy cancer cells and virus infected cells. Some pathogens (Staphylococcus, Streptococcus, and others) are called pyogenic because these microbes induce pus formation; and other microbes are called pyrogenic because these pathogens induce fever. Drugs like tylenol and aspirin (antipyretic drugs) are taken to reset hypothalamus and reduce the body temperature.