Innate immunity

From the discovery of antibodies in the late nineteenth century until very recently, the focus of most research in immunology has been the so-called adaptive immune response. Adaptive immune responses are highly specific for a given microorganism and it is the T and B lymphocytes of the adaptive immune response, and the antibodies produced by the B lymphocytes, that are responsible for lasting immunity after exposure to a pathogen. But an adaptive immune response takes up to a week to develop. The vast majority of infectious microorganisms are eliminated within hours by the cells and molecules of the innate immune system, which recognize common constituents of many microorganisms and are activated immediately on contact, irrespective of prior exposure. There are three arms to the innate defence system: phagocytic cells which ingest invading microorganisms and destroy them; soluble plasma proteins which bind to them and trigger the destructive armory of the complement cascade (see Primer: The complement system, Curr Biol 1998, 8:R259R261); and natural killer cells, which destroy cells infected with intracellular pathogens, most notably viruses. These cells and molecules share the crucial ability to distinguish the infectious (or infected) from the non-infectious (or uninfected), either through receptors that have evolved to recognize common constituents of microorganisms and activate their destruction, or through mechanisms for recognizing common constituents of body cells and inhibiting destruction. The adaptive immune system, which owes its extraordinary versatility to receptors and antibodies that vary at random, does not make this distinction and can in principle engage with any innocent cell or molecule. Harmless entities are usually ignored by the adaptive immune system only because the activation of adaptive immune responses largely depends upon activated cells and molecules of the innate system to trigger it. This has profound implications for the design of vaccines and is one of the reasons for the interest in innate immune recognition.