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 cells, organs, and processes that eliminate pathogens specifically. The acquired immune system is one of the two main immunity strategies found in vertebrates.
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. This acquired response is called "adaptive" because it prepares the body's immune system for future challenges.
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, VJ recombination randomly selects one variable, one diversity,
and one joining 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 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 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
Acquired immunity is triggered in vertebrates when a pathogen evades the innate immune system and generates a threshold level of antigen and 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.
Lymphocytes
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
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. 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, all cells are capable of presenting antigen through the function of major histocompatibility complex 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.
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.