The Innate Immune System

Innate immunity (also known as nonspecific immunity) is a very basic system for dealing with infections that evolved long ago in the ancestor of vertebrates and insects. The adaptive immune system evolved later and is much more sophisticated; it can learn to recognize a threat, mount a response, and remember it later. Innate immunity, in contrast, offers either/or protection: It recognizes and destroys an invader, or it does not. Its main actors are specialized kinds of white blood cells including mast cells, natural killer cells, and macrophages.

An innate immune response begins when the body notices that something is wrong. The alarm is usually sounded by complement proteins; about 20 types of these molecules patrol the bloodstream, looking for a foreign object to dock onto. Such binding has several effects. Some complement proteins act as alarm signals that call up white blood cells, which engulf foreign microbes or diseased cells through endocytosis, described in the previous chapter. A pocket forms in the membrane, and it deepens until the foreign organism is entirely surrounded. The invader is carried to a lysosome, where it is taken apart by enzymes. Sometimes destruction is accomplished by a "respiratory burst": The microbe is exposed to a high-energy form of oxygen that makes an organism's enzymes hyperactive, tearing them apart. Other complement proteins can crack open the membranes of invaders. The cells rupture and die when their contents spill out and molecules from the outside flood the cell.

A different response is triggered by cells that have been infected by a virus. They release proteins called interferons that bind to nearby cells. This activates systems in the neighbor that make it harder for the virus to enter and reproduce.

An additional line of defense involves white blood cell called natural killer cells. They recognize some cells that have been infected by viruses or taken over by cancer. They manage this because the diseased cells do not carry enough of a surface protein called major histocompatibility complex (MHC). Natural killer cells and MHCs are also involved in adaptive immunity and are discussed in more detail below.

Innate immune defenses are enhanced in tissues such as the skin, which comes into contact with the environment, by mast cells that react to damage by releasing histamine proteins. These molecules cause tiny capillaries to swell and leak blood into the surrounding tissue, which is why the site of an injury often undergoes painful swelling. When white blood cells arrive on the scene, they release other signaling proteins called "cytokines." One effect is to tell the brain to raise the body's temperature—a fever. This has an important immune effect because many microbes can only survive in a narrow temperature range; they are usually attuned to normal body temperature. Very high fevers may need to be treated. Suppressing milder fevers might make a person more comfortable, but at the same time it could make the body more hospitable to an invader.

Bacteria and some other infectious agents have evolved methods of slipping by innate immune defenses. The tuberculosis bacterium is enclosed in a shell-like capsule that protects it from being split open by complement proteins. Other parasites enter cells quickly, before they are discovered, then hide and grow inside them. Plasmodium, the one-celled parasite that causes malaria, escapes by growing inside red blood cells. It can only do so in properly formed cells, so people who suffer from sickle-cell anemia, in which red blood cells are improperly built, are at a lower risk of developing malaria.

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