A specific response against infection by potential pathogens, such as the production of antibodies against a particular pathogen, is known as adaptive immunity, because it develops during the lifetime of an individual as an adaptation to infection with that pathogen. Adaptive immunity is distinguished from innate immunity, which was already known at the time von Behring was developing serum therapy for diphtheria chiefly through the work of the great Russian immunologist Elie Metchnikoff, who discovered that many microorganisms could be engulfed and digested by phagocytic cells, which thus provide defenses against infection that are nonspecific. Whereas these cells— which Metchnikoff called 'macrophages'—are always present and ready to act, adaptive immunity requires time to develop but is highly specific.
It was soon clear that specific antibodies could be induced against a vast range of substances, called antigens because they could stimulate antibody generation. Paul Ehrlich advanced the development of an antiserum as a treatment for diphtheria and developed methods to standardize therapeutic serums. Today the term antigen refers to any substance recognized by the adaptive immune system. Typically antigens are common proteins, glycoproteins, and polysaccharides of pathogens, but they can include a much wider range of chemical structures, for example, metals such as nickel, drugs such as penicillin, and organic chemicals such as the urushiol (a mix of pentadecylcatechols) in the leaves of poison ivy. Metchnikoff and Ehrlich shared the 1908 Nobel Prize for their respective work on immunity.
This chapter introduces the principles of innate and adaptive immunity, the cells of the immune system, the tissues in which they develop, and the tissues through which they circulate. We then outline the specialized functions of the different types of cells by which they eliminate infection.
The origins of vertebrate immune cells.
The body is protected from infectious agents, their toxins, and the damage they cause by a variety of effector cells and molecules that together make up the immune system. Both innate and adaptive immune responses depend upon the activities of white blood cells or leukocytes. Most cells of the immune system arise from the bone marrow, where many of them develop and mature. But some, particularly certain tissue-resident macrophage populations (for example, the microglia of the central nervous system), originate from the yolk sack or fetal liver during embryonic development. They seed tissues before birth and are maintained throughout life as independent, self-renewing populations. Once mature, immune cells reside within peripheral tissues, circulate in the bloodstream, or circulate in a specialized system of vessels called
Principles of innate immunity.
the lymphatic system. The lymphatic system drains extracellular fluid and immune cells from tissues and transports them as lymph that is eventually emptied back into the blood system.
All the cellular elements of blood, including the red blood cells that transport oxygen, the platelets that trigger blood clotting in damaged tissues, and the white blood cells of the immune system, ultimately derive from the hematopoietic stem cells (HSCs) of the bone marrow. Because these can give rise to all the different types of blood cells, they are often known as pluripotent hematopoietic stem cells. The hematopoietic stem cells give rise to cells of more limited developmental potential, which are the immediate progenitors of red blood cells, platelets, and the two main categories of white blood cells, the lymphoid and myeloid lineages. The different types of blood cells and their lineage relationships are summarized in Fig. 1.3.
Principles of innate immunity.
In this part of the chapter we will outline the principles of innate immunity and describe the molecules and cells that provide continuous defense against invasion by pathogens. Although the white blood cells known as lymphocytes possess the most powerful ability to recognize and target pathogenic microorganisms, they need the participation of the innate immune system to initiate and mount their offensive. Indeed, the adaptive immune response and innate immunity use many of the same destructive mechanisms to eliminate invading microorganisms.