The features that protect the body against disease are usually considered as successive “lines of defense,” beginning with the relatively simple or outer barriers and proceeding through progressively more complicated responses until the ultimate defense mechanism immunity is reached.
Chemical and Mechanical Barriers
Part of the first line of defense against invaders is the skin, which serves as a mechanical barrier as long as it remains intact. A serious danger to burn victims, for example, is the risk of infection as a result of skin destruction. The mucous membranes that line the passageways leading into the body also act as barriers, trapping foreign material in their sticky secretions. The cilia in membranes in the upper respiratory tract help to sweep impurities out of the body. Body secretions, such as tears, perspiration, and saliva, wash away microorganisms and may contain acids, enzymes, or other chemicals that destroy invaders. Digestive juices destroy many ingested bacteria and their toxins. Certain reflexes aid in the removal of pathogens. Sneezing and coughing, for instance, tend to remove foreign matter, including microorganisms, from the upper respiratory tract. Vomiting and diarrhea are ways in which toxins and bacteria may be expelled.
Phagocytosis is part of the second line of defense against invaders. In the process of phagocytosis, white blood cells take in and destroy waste and foreign material (see Fig. 9-6). Neutrophils and macrophages are the main phagocytic white blood cells. Neutrophils are a type of granular leukocyte. Macrophages are derived from monocytes, a type of agranular leukocyte. Both types of cells travel in the blood to infection sites. Some of the macrophages remain fixed in the tissues, for example, in the skin, liver, lungs, lymphoid tissue, and bone marrow, to fight infection and remove debris.
Figure 9-6 Phagocytosis. (A) A phagocytic leukocyte (white blood cell) squeezes through a capillary wall in the region of an infection and engulfs a bacterium. (B) The bacterium is enclosed in a vesicle and digested by a lysosome.
Natural Killer Cells
The natural killer (NK) cell is a type of lymphocyte different from those active in specific immunity, which are described later. NK cells can recognize body cells with abnormal membranes, such as tumor cells and cells infected with virus, and, as their name indicates, can destroy them on contact. NK cells are found in the lymph nodes, spleen, bone marrow, and blood. They destroy abnormal cells by secreting a protein that breaks down the cell membrane, but the way in which they find their targets is not yet completely understood.
Inflammation is the body’s effort to get rid of anything that irritates it or, if this is not possible, to limit the harmful effects of the irritant. Inflammation can occur as a result of any irritant, not only microorganisms. Friction, fire, chemicals, x-rays, and cuts or blows all can be classified as irritants. If irritation is caused by pathogenic invasion, the resulting inflammation is termed an infection. With the entrance of pathogens and their subsequent multiplication, a whole series of defensive processes begins. This inflammatory reaction is accompanied by four classic symptoms: heat, redness, swelling, and pain, as described below.
When tissues are injured, histamine and other substances are released from the damaged cells, causing the small blood vessels to dilate (widen). More blood then flows into the area, resulting in heat, redness, and swelling. With the increased blood flow come a vast number of leukocytes. Then a new phenomenon occurs: the walls of the tiny blood vessels become “coarsened” in texture (as does a piece of cloth when it is stretched). Blood flow slows down, and the leukocytes move through these altered walls and into the tissue, where they can reach the irritant directly. Fluid from the blood plasma also leaks out of the vessels into the tissues and begins to clot. When this response occurs in a local area, it helps prevent the spread of the foreign agent. The mixture of leukocytes and fluid, the inflammatory exudate, causes pressure on the nerve endings, which combined with the increased amount of blood in the vessels, causes the pain of inflammation.
As the phagocytes do their work, large numbers of them are destroyed, so that eventually the area becomes filled with dead leukocytes. The mixture of exudate, living and dead white blood cells, pathogens, and destroyed tissue cells is pus. Meanwhile, the lymphatic vessels begin to drain fluid from the inflamed area and carry it toward the lymph nodes for filtration. The regional lymph nodes become enlarged and tender, a sign that they are performing their protective function by working overtime to produce phagocytic cells that “clean” the lymph flowing through them.
An increase in body temperature above the normal range can be a sign that body defenses are at work. When phagocytes are exposed to infecting organisms, they release substances that raise body temperature. Fever boosts the immune system in several ways. It stimulates phagocytes, increases metabolism, and decreases certain organisms’ ability to multiply. A common misperception is that fever is a dangerous symptom that should always be eliminated. Control of fever in itself does little to alter the course of an illness. Healthcare workers, however, should always be alert to fever development as a possible sign of a serious disorder and should recognize that an increased metabolic rate may have adverse effects on the hearts of weak patients.
Certain cells infected with a virus release a substance that prevents nearby cells from producing more virus. This substance was first found in cells infected with influenza virus, and it was called interferon because it “interferes” with multiplication and spread of the virus. Interferon is now known to be a group of substances. Each is abbreviated IFN with a Greek letter, alpha, beta, or gamma to indicate the category of interferon and additional letters or numbers to indicate more specific types. Pure interferons are now available in adequate quantities for treatment because they are produced by genetic engineering in microorganisms. They are used to treat certain viral infections, such as hepatitis. Interferons are also of interest because they act nonspecifically on cells of the immune system. They have been used with varying success to boost the immune response in the treatment of malignancies, such as melanoma, leukemia, and Kaposi sarcoma, a cancer associated with AIDS. Interestingly, interferon b is used to treat the autoimmune disorder multiple sclerosis (MS), because it stimulates cells that depress the immune response.