Adaptive immune system
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The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the
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.[1]
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.[citation needed]
The cells that carry out the adaptive immune response are white blood cells known as
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
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".[citation needed]
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.[citation needed]
Functions
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
The major functions of the acquired immune system include:[citation needed]
- 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.[4]
Lymphocytes
T and B
B cells and T cells are derived from the same
In an adult animal, the peripheral lymphoid organs contain a mixture of B and T cells in at least three stages of differentiation:[citation needed]
- 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
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"
With the exception of non-nucleated cells (including
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.[3]
Exogenous antigens
Dendritic cells engulf
Endogenous antigens
T lymphocytes
CD8+ T lymphocytes and cytotoxicity
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.[3]
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.[3] 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.[citation needed]
When exposed to these infected or dysfunctional
On resolution of the infection, most effector cells die and phagocytes clear them away—but a few of these cells remain as memory cells.[6] 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.[citation needed]
Helper T-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.[3] These cells have no cytotoxic or phagocytic activity; and cannot kill infected cells or clear pathogens, but, in essence "manage" the immune response, by directing other cells to perform these tasks.[citation needed]
Helper T cells express T cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. The activation of a naive helper T-cell causes it to release cytokines, which influences the activity of many cell types, including the APC (Antigen-Presenting Cell) that activated it. Helper T-cells require a much milder activation stimulus than cytotoxic T cells. Helper T cells can provide extra signals that "help" activate cytotoxic cells.[6]
Th1 and Th2: helper T cell responses
Classically, two types of effector CD4+ T helper cell responses can be induced by a professional APC, designated Th1 and Th2, each designed to eliminate different types of pathogens. The factors that dictate whether an infection triggers a Th1 or Th2 type response are not fully understood, but the response generated does play an important role in the clearance of different pathogens.[3]
The Th1 response is characterized by the production of
The Th2 response is characterized by the release of
Like cytotoxic T cells, most of the CD4+ helper cells die on resolution of infection, with a few remaining as CD4+ memory cells.Increasingly, there is strong evidence from mouse and human-based scientific studies of a broader diversity in CD4+ effector T helper cell subsets.
The relevance of CD4+ T helper cells is highlighted during an HIV infection. HIV is able to subvert the immune system by specifically attacking the CD4+ T cells, precisely the cells that could drive the clearance of the virus, but also the cells that drive immunity against all other pathogens encountered during an organism's lifetime.[6]
Gamma delta T cells
B lymphocytes and antibody production
B Cells are the major cells involved in the creation of
Antigen and antibody binding would cause five different protective mechanisms:
- Agglutination: Reduces number of infectious units to be dealt with
- Activation of complement: Cause inflammation and cell lysis
- Opsonization: Coating antigen with antibody enhances phagocytosis
- Antibody-dependent cell-mediated cytotoxicity: Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells
- Neutralization: Blocks adhesion of bacteria and viruses to mucosa
Like the T cell, B cells express a unique B cell receptor (BCR), in this case, a membrane-bound antibody molecule. All the BCR of any one clone of B cells recognizes and binds to only one particular antigen. A critical difference between B cells and T cells is how each cell "sees" an antigen. T cells recognize their cognate antigen in a processed form – as a peptide in the context of an MHC molecule,
Alternative systems
In jawless vertebrates
Primitive
In insects
For a long time it was thought that
Immune memory in insects was discovered through the phenomenon of priming. When insects are exposed to non-lethal dose or heat killed bacteria they are able to develop a memory of that infection that allows them to withstand otherwise lethal dose of the same bacteria they were exposed to before.[15][16] Unlike in vertebrates, insects do not possess cells specific for adaptive immunity. Instead those mechanisms are mediated by hemocytes. Hemocytes function similarly to phagocytes and after priming they are able to more effectively recognize and engulf the pathogen.[17] It was also shown that it is possible to transfer the memory into offspring. For example, in honeybees if the queen is infected with bacteria then the newly born workers have enhanced abilities in fighting with the same bacteria.[18] Other experimental model based on red flour beetle also showed pathogen specific primed memory transfer into offspring from both mothers and fathers.[19]
Most commonly accepted theory of the specificity is based on Dscam gene. Dscam gene also known as Down syndrome cell adhesive molecule is a gene that contains 3 variable Ig domains. Those domains can be alternatively spliced reaching high numbers of variations.[20] It was shown that after exposure to different pathogens there are different splice forms of dscam produced. After the animals with different splice forms are exposed to the same pathogen only the individuals with the splice form specific for that pathogen survive.[20]
Other mechanisms supporting the specificity of insect immunity is
Immunological memory
When B cells and T cells are activated some become memory B cells and some memory T cells. Throughout the lifetime of an animal these memory cells form a database of effective B and T lymphocytes. Upon interaction with a previously encountered antigen, the appropriate memory cells are selected and activated. In this manner, the second and subsequent exposures to an antigen produce a stronger and faster immune response. This is "adaptive" in the sense that the body's immune system prepares itself for future challenges, but is "maladaptive" of course if the receptors are autoimmune. Immunological memory can be in the form of either passive short-term memory or active long-term memory.[citation needed]
Passive memory
Passive memory is usually short-term, lasting between a few days and several months. Newborn
This is
Active memory
In general, active immunity is long-term and can be acquired by infection followed by B cell and T cell activation, or artificially acquired by vaccines, in a process called immunization.
Immunization
Historically, infectious disease has been the leading cause of death in the human population. Over the last century, two important factors have been developed to combat their spread: sanitation and immunization.[6] Immunization (commonly referred to as vaccination) is the deliberate induction of an immune response, and represents the single most effective manipulation of the immune system that scientists have developed.[6] Immunizations are successful because they utilize the immune system's natural specificity as well as its inducibility.[citation needed]
The principle behind immunization is to introduce an antigen, derived from a disease-causing organism, that stimulates the immune system to develop protective immunity against that organism, but that does not itself cause the pathogenic effects of that organism. An antigen (short for antibody generator), is defined as any substance that binds to a specific antibody and elicits an adaptive immune response.[2]
Most viral
Immunological diversity
Most large molecules, including virtually all proteins and many polysaccharides, can serve as antigens.[3] The parts of an antigen that interact with an antibody molecule or a lymphocyte receptor, are called epitopes, or antigenic determinants. Most antigens contain a variety of epitopes and can stimulate the production of antibodies, specific T cell responses, or both.[3] A very small proportion (less than 0.01%) of the total lymphocytes are able to bind to a particular antigen, which suggests that only a few cells respond to each antigen.[6]
For the acquired response to "remember" and eliminate a large number of pathogens the immune system must be able to distinguish between many different antigens,[2] and the receptors that recognize antigens must be produced in a huge variety of configurations, in essence one receptor (at least) for each different pathogen that might ever be encountered. Even in the absence of antigen stimulation, a human can produce more than 1 trillion different antibody molecules.[6] Millions of genes would be required to store the genetic information that produces these receptors, but, the entire human genome contains fewer than 25,000 genes.[23]
Myriad receptors are produced through a process known as clonal selection.[2][3] According to the clonal selection theory, at birth, an animal randomly generates a vast diversity of lymphocytes (each bearing a unique antigen receptor) from information encoded in a small family of genes. To generate each unique antigen receptor, these genes have undergone a process called V(D)J recombination, or combinatorial diversification, in which one gene segment recombines with other gene segments to form a single unique gene. This assembly process generates the enormous diversity of receptors and antibodies, before the body ever encounters antigens, and enables the immune system to respond to an almost unlimited diversity of antigens.[3] Throughout an animal's lifetime, lymphocytes that can react against the antigens an animal actually encounters are selected for action—directed against anything that expresses that antigen.[citation needed]
The innate and acquired portions of the immune system work together, not in spite of each other. The acquired arm, B, and T cells could not function without the innate system input. T cells are useless without antigen-presenting cells to activate them, and B cells are disabled without T cell help. On the other hand, the innate system would likely be overrun with pathogens without the specialized action of the adaptive immune response.
Acquired immunity during pregnancy
The cornerstone of the immune system is the recognition of "self" versus "non-self". Therefore, the mechanisms that protect the human
During pregnancy in
The
Immune network theory
A theoretical framework explaining the workings of the acquired immune system is provided by
Stimulation of adaptive immunity
One of the most interesting developments in biomedical science during the past few decades has been elucidation of mechanisms mediating innate immunity. One set of innate immune mechanisms is humoral, such as complement activation. Another set comprises pattern recognition receptors such as toll-like receptors, which induce the production of interferons and other cytokines increasing resistance of cells such as monocytes to infections.[27] Cytokines produced during innate immune responses are among the activators of adaptive immune responses.[27] Antibodies exert additive or synergistic effects with mechanisms of innate immunity. Unstable HbS clusters Band-3, a major integral red cell protein;[28] antibodies recognize these clusters and accelerate their removal by phagocytic cells. Clustered Band 3 proteins with attached antibodies activate complement, and complement C3 fragments are opsonins recognized by the CR1 complement receptor on phagocytic cells.[29]
A population study has shown that the protective effect of the sickle-cell trait against falciparum malaria involves the augmentation of acquired as well as innate immune responses to the malaria parasite, illustrating the expected transition from innate to acquired immunity.[30]
Repeated malaria infections strengthen acquired immunity and broaden its effects against parasites expressing different surface antigens. By school age most children have developed efficacious adaptive immunity against malaria. These observations raise questions about mechanisms that favor the survival of most children in Africa while allowing some to develop potentially lethal infections.
In malaria, as in other infections,[27] innate immune responses lead into, and stimulate, adaptive immune responses. The genetic control of innate and acquired immunity is now a large and flourishing discipline.
Humoral and cell-mediated immune responses limit malaria parasite multiplication, and many cytokines contribute to the pathogenesis of malaria as well as to the resolution of infections.[31]
Evolution
The acquired immune system, which has been best-studied in mammals, originated in jawed fish approximately 500 million years ago. Most of the molecules, cells, tissues, and associated mechanisms of this system of defense are found in
Lymphoid cells can be identified in some pre-vertebrate
The evolution of the AIS, based on Ig, TCR, and MHC molecules, is thought to have arisen from two major evolutionary events: the transfer of the
Types of acquired immunity
Immunity can be acquired either actively or passively. Immunity is acquired actively when a person is exposed to foreign substances and the immune system responds. Passive immunity is when antibodies are transferred from one host to another. Both actively acquired and passively acquired immunity can be obtained by natural or artificial means.
- Naturally Acquired Active Immunity – when a person is naturally exposed to antigens, becomes ill, then recovers.
- Naturally Acquired Passive Immunity – involves a natural transfer of antibodies from a mother to her infant. The antibodies cross the woman's placenta to the fetus. Antibodies can also be transferred through breast milk with the secretions of colostrum.
- Artificially Acquired Active Immunity – is done by vaccination (introducing dead or weakened antigen to the host's cell).
- Artificially Acquired Passive Immunity – This involves the introduction of antibodies rather than antigens to the human body. These antibodies are from an animal or person who is already immune to the disease.
Naturally acquired | Artificially acquired |
---|---|
Active – Antigen enters the body naturally | Active – Antigens are introduced in vaccines. |
Passive – Antibodies pass from mother to fetus via placenta or infant via the mother's milk. | Passive – Preformed antibodies in immune serum are introduced by injection. |
See also
- Affinity maturation
- Allelic exclusion
- Anergy
- Immune response
- Immune tolerance
- Immunosuppression
- Original antigenic sin
- Somatic hypermutation
- Polyclonal response
Notes and references
- Notes
- References
- ^ The innate and adaptive immune systems. Institute for Quality and Efficiency in Health Care (IQWiG). 4 August 2016.
- ^ ISBN 0-8153-3218-1.
- ^ ISBN 0-8153-4101-6.
- ^ Charles A Janeway, Jr; Travers, Paul; Walport, Mark; Shlomchik, Mark J. (2001). "Principles of innate and adaptive immunity". Immunobiology: The Immune System in Health and Disease. 5th Edition.
- ^ "Microbiology and Immunology On-Line Textbook". University of South Carolina School of Medicine. Archived from the original on 2 September 2008.
- ^ ISBN 0-443-07310-4.
- ^ a b c "Understanding the Immune System How It Works" (PDF). NIH Publication No. 03-5423. National Institute of Allergy and Infectious Diseases National Cancer Institute, U.S. Department of Health and Human Services National Institutes of Health. September 2003. Archived from the original (PDF) on 2007-01-03.
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- ^ Villarreal LP. "The Viruses That Make Us: A Role For Endogenous Retrovirus In The Evolution Of Placental Species". University of California, Irvine (lecture notes). Archived from the original on 2007-07-15. Retrieved 2008-02-03.
- ^ Villarreal LP (Oct 2001). "Persisting Viruses Could Play Role in Driving Host Evolution". ASM News. Archived from the original on 2009-05-08.
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