adaptive immune system adaptive immune system the adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. the acquired immune system is one of the two main immunity strategies found in vertebrates (the other being the innate immune system). google ngram of "acquired immunity " vs. "adaptive immunity". the peak for "adaptive" in the 1960s reflects its introduction to immunology by robert a. good and use by colleagues; the explosive increase in the 1990s was correlated with the use of the phrase "innate immunity". a scanning electron microscope image of a single human lymphocyte like the innate system, the adaptive immune system includes both humoral immunity components and cell-mediated immunity components and destroys invading pathogens. unlike the innate immune system, which is pre-programmed to react to common broad categories of pathogen, the adaptive immune system is highly specific to each particular pathogen the body has encountered. adaptive immunity creates immunological memory after an initial response to a specific pathogen, and leads to an enhanced response to future encounters with that pathogen. antibodies are a critical part of the adaptive immune system. adaptive immunity can provide long-lasting protection, sometimes for the person's entire lifetime. for example, someone who recovers from measles is now protected against measles for their lifetime; in other cases it does not provide lifetime protection, as with chickenpox. this process of adaptive immunity is the basis of vaccination. the cells that carry out the adaptive immune response are white blood cells known as lymphocytes. b cells and t cells, two different types of lymphocytes, carry out the main activities: antibody responses, and cell-mediated immune response. in antibody responses, b cells are activated to secrete antibodies, which are proteins also known as immunoglobulins. antibodies travel through the bloodstream and bind to the foreign antigen causing it to inactivate, which does not allow the antigen to bind to the host. antigens are any substances that elicit the adaptive immune response. sometimes the adaptive system is unable to distinguish harmful from harmless foreign molecules; the effects of this may be hayfever, asthma, or any other allergy. in adaptive immunity, pathogen-specific receptors are "acquired" during the lifetime of the organism (whereas in innate immunity pathogen-specific receptors are already encoded in the genome). this acquired response is called "adaptive" because it prepares the body's immune system for future challenges (though it can actually also be maladaptive when it results in allergies or autoimmunity). the system is highly adaptable because of two factors. first, somatic hypermutation is a process of accelerated random genetic mutations in the antibody-coding genes, which allows antibodies with novel specificity to be created. second, v(d)j recombination randomly selects one variable (v), one diversity (d), and one joining (j) region for genetic recombination and discards the rest, which produces a highly unique combination of antigen-receptor gene segments in each lymphocyte. this mechanism allows a small number of genetic segments to generate a vast number of different antigen receptors, which are then uniquely expressed on each individual lymphocyte. since the gene rearrangement leads to an irreversible change in the dna of each cell, all progeny (offspring) of that cell inherit genes that encode the same receptor specificity, including the memory b cells and memory t cells that are the keys to long-lived specific immunity. naming the term "adaptive" was first used by robert good in reference to antibody responses in frogs as a synonym for "acquired immune response" in 1964. good acknowledged he used the terms as synonyms but explained only that he preferred to use the term "adaptive". he might have been thinking of the then not implausible theory of antibody formation in which antibodies were plastic and could adapt themselves to the molecular shape of antigens, and/or to the concept of "adaptive enzymes" as described by monod in bacteria, that is, enzymes whose expression could be induced by their substrates. the phrase was used almost exclusively by good and his students and a few other immunologists working with marginal organisms until the 1990s when it became widely used in tandem with the term "innate immunity" which became a popular subject after the discovery of the toll receptor system in drosophila, a previously marginal organism for the study of immunology. the term "adaptive" as used in immunology is problematic as acquired immune responses can be both adaptive and maladaptive in the physiological sense. indeed, both acquired and innate immune responses can be both adaptive and maladaptive in the evolutionary sense. most textbooks today, following the early use by janeway, use "adaptive" almost exclusively and noting in glossaries that the term is synonymous with "acquired". the classic sense of "acquired immunity" came to mean, since tonegawa's discovery, "antigen-specific immunity mediated by somatic gene rearrangements that create clone-defining antigen receptors". in the last decade, the term "adaptive" has been increasingly applied to another class of immune response not so-far associated with somatic gene rearrangements. these include expansion of natural killer (nk) cells with so-far unexplained specificity for antigens, expansion of nk cells expressing germ-line encoded receptors, and activation of other innate immune cells to an activated state that confers a short-term "immune memory". in this sense, "adaptive immunity" more closely resembles the concept of "activated state" or "heterostasis", thus returning in sense to the physiological sense of "adaptation" to environmental changes. functions overview of the processes involved in the primary immune response acquired immunity is triggered in vertebrates when a pathogen evades the innate immune system and (1) generates a threshold level of antigen and (2) generates "stranger" or "danger" signals activating dendritic cells. the major functions of the acquired immune system include: recognition of specific "non-self" antigens in the presence of "self", during the process of antigen presentation. generation of responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells. development of immunological memory, in which pathogens are "remembered" through memory b cells and memory t cells. in humans, it takes 4–7 days for the adaptive immune system to mount a significant response. lymphocytes main article: lymphocyte t and b lymphocytes are the cells of the adaptive immune system. the human body has about 2 trillion lymphocytes, which are 20–40% of white blood cells; their total mass is about the same as the brain or liver. the peripheral bloodstream contains only 2% of all circulating lymphocytes; the other 98% move within tissues and the lymphatic system, which includes the lymph nodes and spleen. in humans, approximately 1–2% of the lymphocyte pool recirculates each hour to increase the opportunity for the cells to encounter the specific pathogen and antigen that they react to. b cells and t cells are derived from the same multipotent hematopoietic stem cells, and look identical to one another until after they are activated. b cells play a large role in the humoral immune response, whereas t cells are intimately involved in cell-mediated immune responses. in all vertebrates except agnatha, b cells and t cells are produced by stem cells in the bone marrow. t cell progenitors then migrate from the bone marrow to the thymus, where they develop further. in an adult animal, the peripheral lymphoid organs contain a mixture of b and t cells in at least three stages of differentiation: naive b and naive t cells, which have left the bone marrow or thymus and entered the lymphatic system, but have yet to encounter their matching antigen effector cells that have been activated by their matching antigen, and are actively involved in eliminating a pathogen memory cells, the survivors of past infections antigen presentation main article: antigen presentation acquired immunity relies on the capacity of immune cells to distinguish between the body's own cells and unwanted invaders. the host's cells express "self" antigens. these antigens are different from those on the surface of bacteria or on the surface of virus-infected host cells ("non-self" or "foreign" antigens). the acquired immune response is triggered by recognizing foreign antigen in the cellular context of an activated dendritic cell. with the exception of non-nucleated cells (including erythrocytes), all cells are capable of presenting antigen through the function of major histocompatibility complex (mhc) molecules. some cells are specially equipped to present antigen, and to prime naive t cells. dendritic cells, b-cells, and macrophages are equipped with special "co-stimulatory" ligands recognized by co-stimulatory receptors on t cells, and are termed professional antigen-presenting cells (apcs). several t cells subgroups can be activated by professional apcs, and each type of t cell is specially equipped to deal with each unique toxin or microbial pathogen. the type of t cell activated, and the type of response generated, depends, in part, on the context in which the apc first encountered the antigen. exogenous antigens antigen presentation stimulates t cells to become either "cytotoxic" cd8+ cells or "helper" cd4+ cells. dendritic cells engulf exogenous pathogens, such as bacteria, parasites or toxins in the tissues and then migrate, via chemotactic signals, to the t cell-enriched lymph nodes. during migration, dendritic cells undergo a process of maturation in which they lose most of their ability to engulf other pathogens, and develop an ability to communicate with t-cells. the dendritic cell uses enzymes to chop the pathogen into smaller pieces, called antigens. in the lymph node, the dendritic cell displays these non-self antigens on its surface by coupling them to a receptor called the major histocompatibility complex, or mhc (also known in humans as human leukocyte antigen (hla)). this mhc-antigen complex is recognized by t-cells passing through the lymph node. exogenous antigens are usually displayed on mhc class ii molecules, which activate cd4+t helper cells. endogenous antigens endogenous antigens are produced by intracellular bacteria and viruses replicating within a host cell. the host cell uses enzymes to digest virally associated proteins and displays these pieces on its surface to t-cells by coupling them to mhc. endogenous antigens are typically displayed on mhc class i molecules, and activate cd8+ cytotoxic t-cells. with the exception of non-nucleated cells (including erythrocytes), mhc class i is expressed by all host cells. t lymphocytes main article: t cell cd8+ t lymphocytes and cytotoxicity main article: cytotoxic t cell cytotoxic t cells (also known as tc, killer t cell, or cytotoxic t-lymphocyte (ctl)) are a sub-group of t cells that induce the death of cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. naive cytotoxic t cells are activated when their t-cell receptor (tcr) strongly interacts with a peptide-bound mhc class i molecule. this affinity depends on the type and orientation of the antigen/mhc complex, and is what keeps the ctl and infected cell bound together. once activated, the ctl undergoes a process called clonal selection, in which it gains functions and divides rapidly to produce an army of "armed" effector cells. activated ctl then travels throughout the body searching for cells that bear that unique mhc class i + peptide. when exposed to these infected or dysfunctional somatic cells, effector ctl release perforin and granulysin: cytotoxins that form pores in the target cell's plasma membrane, allowing ions and water to flow into the infected cell, and causing it to burst or lyse. ctl release granzyme, a serine protease encapsulated in a granule that enters cells via pores to induce apoptosis (cell death). to limit extensive tissue damage during an infection, ctl activation is tightly controlled and in general requires a very strong mhc/antigen activation signal, or additional activation signals provided by "helper" t-cells (see below). on resolution of the infection, most effector cells die and phagocytes clear them away—but a few of these cells remain as memory cells. on a later encounter with the same antigen, these memory cells quickly differentiate into effector cells, dramatically shortening the time required to mount an effective response. helper t-cells main article: t helper cell the t lymphocyte activation pathway. t cells contribute to immune defenses in two major ways: some direct and regulate immune responses; others directly attack infected or cancerous cells. cd4+ lymphocytes, also called "helper" t cells, are immune response mediators, and play an important role in establishing and maximizing the capabilities of the acquired immune response. these cells have no cytotoxic or phagocytic activity; and cannot kill infected