Immune system

Source: Wikipedia, the free encyclopedia.
(Redirected from
Immune systems
)

See caption
A scanning electron microscope image of a single neutrophil (yellow/right), engulfing anthrax bacteria (orange/left) – scale bar is 5 µm (false color)

The immune system is a network of

tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells
to perform their functions.

Nearly all organisms have some kind of immune system.

Jawed vertebrates, including humans, have even more sophisticated defense mechanisms, including the ability to adapt to recognize pathogens more efficiently. Adaptive (or acquired) immunity creates an immunological memory leading to an enhanced response to subsequent encounters with that same pathogen. This process of acquired immunity is the basis of vaccination
.

Dysfunction of the immune system can cause

covers the study of all aspects of the immune system.

Layered defense

The immune system protects its host from infection with layered defenses of increasing specificity. Physical barriers prevent pathogens such as bacteria and viruses from entering the organism.[1] If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response. Innate immune systems are found in all animals.[2] If pathogens successfully evade the innate response, vertebrates possess a second layer of protection, the adaptive immune system, which is activated by the innate response.[3] Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered.[4][5]

Components of the immune system
Innate immune system Adaptive immune system
Response is non-specific Pathogen and antigen specific response
Exposure leads to immediate maximal response Lag time between exposure and maximal response
humoral
components
humoral
components
No immunological memory Exposure leads to immunological memory
Found in nearly all forms of life Found only in jawed vertebrates

Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self molecules. In immunology, self molecules are components of an organism's body that can be distinguished from foreign substances by the immune system.[6] Conversely, non-self molecules are those recognized as foreign molecules. One class of non-self molecules are called antigens (originally named for being antibody generators) and are defined as substances that bind to specific immune receptors and elicit an immune response.[7]

Surface barriers

Several barriers protect organisms from infection, including mechanical, chemical, and biological barriers. The waxy

intestines, and the genitourinary tract. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the respiratory tract. The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.[9]

Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β-defensins.[10] Enzymes such as lysozyme and phospholipase A2 in saliva, tears, and breast milk are also antibacterials.[11][12] Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains defensins and zinc to kill pathogens.[13][14] In the stomach, gastric acid serves as a chemical defense against ingested pathogens.[15]

Within the genitourinary and gastrointestinal tracts,

flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, changing the conditions in their environment, such as pH or available iron. As a result, the probability that pathogens will reach sufficient numbers to cause illness is reduced.[16]

Innate immune system

Microorganisms or toxins that successfully enter an organism encounter the cells and mechanisms of the innate immune system. The innate response is usually triggered when microbes are identified by

immunity against a pathogen. The innate immune system is the dominant system of host defense in most organisms,[2] and the only one in plants.[20]

Immune sensing

Cells in the innate immune system use

damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or cell death.[23]

Recognition of extracellular or endosomal PAMPs is mediated by transmembrane proteins known as toll-like receptors (TLRs).[24] TLRs share a typical structural motif, the leucine rich repeats (LRRs), which give them a curved shape.[25] Toll-like receptors were first discovered in Drosophila and trigger the synthesis and secretion of cytokines and activation of other host defense programs that are necessary for both innate or adaptive immune responses. Ten toll-like receptors have been described in humans.[26]

Cells in the innate immune system have pattern recognition receptors, which detect infection or cell damage, inside. Three major classes of these "cytosolic" receptors are NOD–like receptors, RIG (retinoic acid-inducible gene)-like receptors, and cytosolic DNA sensors.[27]

Innate immune cells

See caption
A scanning electron microscope image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.

Some

basophils, and natural killer cells.[28]

vesicle called a phagosome, which subsequently fuses with another vesicle called a lysosome to form a phagolysosome. The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome.[30][31] Phagocytosis evolved as a means of acquiring nutrients, but this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism.[32] Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals.[33]

Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading pathogens.[34] Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, representing 50% to 60% of total circulating leukocytes.[35] During the acute phase of inflammation, neutrophils migrate toward the site of inflammation in a process called chemotaxis, and are usually the first cells to arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and produce an array of chemicals including enzymes, complement proteins, and cytokines, while they can also act as scavengers that rid the body of worn-out cells and other debris, and as antigen-presenting cells (APCs) that activate the adaptive immune system.[36]

Dendritic cells are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines.[37] They are named for their resemblance to neuronal dendrites, as both have many spine-like projections. Dendritic cells serve as a link between the bodily tissues and the innate and adaptive immune systems, as they present antigens to T cells, one of the key cell types of the adaptive immune system.[37]

Granulocytes are leukocytes that have granules in their cytoplasm. In this category are neutrophils, mast cells, basophils, and eosinophils. Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response.[38] They are most often associated with allergy and anaphylaxis.[35] Basophils and eosinophils are related to neutrophils. They secrete chemical mediators that are involved in defending against parasites and play a role in allergic reactions, such as asthma.[39]

Innate lymphoid cells (ILCs) are a group of

recombination activating gene. ILCs do not express myeloid or dendritic cell markers.[40]

Natural killer cells (NK cells) are lymphocytes and a component of the innate immune system which does not directly attack invading microbes.[41] Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by a condition known as "missing self". This term describes cells with low levels of a cell-surface marker called MHC I (major histocompatibility complex)—a situation that can arise in viral infections of host cells.[42] Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens are recognized by killer cell immunoglobulin receptors which essentially put the brakes on NK cells.[43]

Inflammation

Inflammation is one of the first responses of the immune system to infection.

dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes).[45][46] Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell.[47] Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.[48] The pattern-recognition receptors called inflammasomes are multiprotein complexes (consisting of an NLR, the adaptor protein ASC, and the effector molecule pro-caspase-1) that form in response to cytosolic PAMPs and DAMPs, whose function is to generate active forms of the inflammatory cytokines IL-1β and IL-18.[49]

Humoral defenses

The complement system is a

microbes. This recognition signal triggers a rapid killing response.[53] The speed of the response is a result of signal amplification that occurs after sequential proteolytic activation of complement molecules, which are also proteases. After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other complement proteases, and so on. This produces a catalytic cascade that amplifies the initial signal by controlled positive feedback.[54] The cascade results in the production of peptides that attract immune cells, increase vascular permeability, and opsonize (coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their plasma membrane via the formation of a membrane attack complex.[50]

Adaptive immune system

diagram showing the processes of activation, cell destruction and digestion, antibody production and proliferation, and response memory
Overview of the processes involved in the primary immune response

The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by a signature antigen.[55] The adaptive immune response is antigen-specific and requires the recognition of specific "non-self" antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.[56]

Recognition of antigen

The cells of the adaptive immune system are special types of leukocytes, called lymphocytes.

γδ T cells that recognize intact antigens that are not bound to MHC receptors.[58] The double-positive T cells are exposed to a wide variety of self-antigens in the thymus, in which iodine is necessary for its thymus development and activity.[59] In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface and recognizes native (unprocessed) antigen without any need for antigen processing. Such antigens may be large molecules found on the surfaces of pathogens, but can also be small haptens (such as penicillin) attached to carrier molecule.[60] Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.[57] When B or T cells encounter their related antigens they multiply and many "clones" of the cells are produced that target the same antigen. This is called clonal selection.[61]

Antigen presentation to T lymphocytes

Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a "non-self" target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a "self" receptor called a major histocompatibility complex (MHC) molecule.[62]

Cell mediated immunity

There are two major subtypes of T cells: the

regulatory T cells which have a role in modulating immune response.[63]

Killer T cells

granulysin (a protease) induces the target cell to undergo apoptosis.[65] T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T cells (see below).[65]

Helper T cells

Activation of macrophage or B cell by T helper cell

Helper T cells regulate both the innate and adaptive immune responses and help determine which immune responses the body makes to a particular pathogen.[66][67] These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the immune response by directing other cells to perform these tasks.[68]

Helper T cells express T cell receptors that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex is also recognized by the helper cell's CD4 co-receptor, which recruits molecules inside the T cell (such as Lck) that are responsible for the T cell's activation. Helper T cells have a weaker association with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200–300) on the helper T cell must be bound by an MHC:antigen to activate the helper cell, while killer T cells can be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell.[69] The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells.[70] In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell's surface, such as CD40 ligand (also called CD154), which provide extra stimulatory signals typically required to activate antibody-producing B cells.[71]

Gamma delta T cells

CD1d-restricted natural killer T cells, γδ T cells straddle the border between innate and adaptive immunity.[72] On one hand, γδ T cells are a component of adaptive immunity as they rearrange TCR genes to produce receptor diversity and can also develop a memory phenotype. On the other hand, the various subsets are also part of the innate immune system, as restricted TCR or NK receptors may be used as pattern recognition receptors. For example, large numbers of human Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted Vδ1+ T cells in epithelia respond to stressed epithelial cells.[58]

Humoral immune response

diagram showing the Y-shaped antibody. The variable region, including the antigen-binding site, is the top part of the two upper light chains. The remainder is the constant region.
An antibody is made up of two heavy chains and two light chains. The unique variable region allows an antibody to recognize its matching antigen.[73]

A

plasma cells) secrete millions of copies of the antibody that recognizes this antigen. These antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen and mark them for destruction by complement activation or for uptake and destruction by phagocytes. Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells.[76]

Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. During pregnancy, a particular type of antibody, called

transferred artificially from one individual to another.[79]

Immunological memory

When B cells and T cells are activated and begin to replicate, some of their offspring become long-lived memory cells. Throughout the lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again. T-cells recognize pathogens by small protein-based infection signals, called antigens, that bind to directly to T-cell surface receptors.[80] B-cells use the protein, immunoglobulin, to recognize pathogens by their antigens. [81] This is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges. Immunological memory can be in the form of either passive short-term memory or active long-term memory.[82]

Physiological regulation

The initial response involves antibody and effector T-cells. The resulting protective immunity lasts for weeks. Immunological memory often lasts for years.
The time-course of an immune response begins with the initial pathogen encounter, (or initial vaccination) and leads to the formation and maintenance of active immunological memory.

The immune system is involved in many aspects of physiological regulation in the body. The immune system interacts intimately with other systems, such as the

embryogenesis (development of the embryo), as well as in tissue repair and regeneration.[88]

Hormones

immunosuppressive.[91] Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D.[92][93]

Vitamin D

Although cellular studies indicate that vitamin D has receptors and probable functions in the immune system, there is no

autoimmune disorders, and infections ... could not be linked reliably with calcium or vitamin D intake and were often conflicting."[95]
: 5 

Sleep and rest

The immune system is affected by sleep and rest, and

REM) sleep.[97] Thus the immune response to infection may result in changes to the sleep cycle, including an increase in slow-wave sleep relative to REM sleep.[98]

In people with sleep deprivation, active immunizations may have a diminished effect and may result in lower antibody production, and a lower immune response, than would be noted in a well-rested individual.[99] Additionally, proteins such as NFIL3, which have been shown to be closely intertwined with both T-cell differentiation and circadian rhythms, can be affected through the disturbance of natural light and dark cycles through instances of sleep deprivation. These disruptions can lead to an increase in chronic conditions such as heart disease, chronic pain, and asthma.[100]

In addition to the negative consequences of sleep deprivation, sleep and the intertwined circadian system have been shown to have strong regulatory effects on immunological functions affecting both innate and adaptive immunity. First, during the early slow-wave-sleep stage, a sudden drop in blood levels of

Th1/Th2 cytokine balance towards one that supports Th1, an increase in overall Th cell proliferation, and naïve T cell migration to lymph nodes. This is also thought to support the formation of long-lasting immune memory through the initiation of Th1 immune responses.[101]

During wake periods, differentiated effector cells, such as cytotoxic natural killer cells and cytotoxic T lymphocytes, peak to elicit an effective response against any intruding pathogens. Anti-inflammatory molecules, such as cortisol and catecholamines, also peak during awake active times. Inflammation would cause serious cognitive and physical impairments if it were to occur during wake times, and inflammation may occur during sleep times due to the presence of melatonin. Inflammation causes a great deal of oxidative stress and the presence of melatonin during sleep times could actively counteract free radical production during this time.[101][102]

Physical exercise

Physical exercise has a positive effect on the immune system and depending on the frequency and intensity, the pathogenic effects of diseases caused by bacteria and viruses are moderated.[103] Immediately after intense exercise there is a transient immunodepression, where the number of circulating lymphocytes decreases and antibody production declines. This may give rise to a window of opportunity for infection and reactivation of latent virus infections,[104] but the evidence is inconclusive.[105][106]

Changes at the cellular level

Four neutrophils in a Giemsa-stained blood film

During exercise there is an increase in circulating

neutrophils in the blood increases and remains raised for up to six hours and immature forms are present. Although the increase in neutrophils ("neutrophilia") is similar to that seen during bacterial infections, after exercise the cell population returns to normal by around 24 hours.[104]

The number of circulating

natural killer cells) decreases during intense exercise but returns to normal after 4 to 6 hours. Although up to 2% of the cells die most migrate from the blood to the tissues, mainly the intestines and lungs, where pathogens are most likely to be encountered.[104]

Some monocytes leave the blood circulation and migrate to the muscles where they differentiate and become macrophages.[104] These cells differentiate into two types: proliferative macrophages, which are responsible for increasing the number of stem cells and restorative macrophages, which are involved their maturing to muscle cells.[107]

Repair and regeneration

The immune system, particularly the innate component, plays a decisive role in tissue repair after an insult. Key actors include macrophages and neutrophils, but other cellular actors, including γδ T cells, innate lymphoid cells (ILCs), and regulatory T cells (Tregs), are also important. The plasticity of immune cells and the balance between pro-inflammatory and anti-inflammatory signals are crucial aspects of efficient tissue repair. Immune components and pathways are involved in regeneration as well, for example in amphibians such as in axolotl limb regeneration. According to one hypothesis, organisms that can regenerate (e.g., axolotls) could be less immunocompetent than organisms that cannot regenerate.[108]

Disorders of human immunity

Failures of host defense occur and fall into three broad categories: immunodeficiencies,[109] autoimmunity,[110] and hypersensitivities.[111]

Immunodeficiencies

AIDS and some types of cancer cause acquired immunodeficiency.[117][118]

Autoimmunity

See caption
Joints of a hand swollen and deformed by rheumatoid arthritis, an autoimmune disorder

Overactive immune responses form the other end of immune dysfunction, particularly the

systemic lupus erythematosus.[123]

Hypersensitivity

basophils when cross-linked by antigen.[124]
Type II hypersensitivity occurs when antibodies bind to antigens on the individual's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies.[124] Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions.[124] Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis. These reactions are mediated by T cells, monocytes, and macrophages.[124]

Idiopathic inflammation

Inflammation is one of the first responses of the immune system to infection,[44] but it can appear without known cause.

Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes).[45][46] Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell.[47] Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.[48]

Manipulation in medicine

Skeletal structural formula of dexamethasone, C22 H29 F O5
Skeletal structural formula of the immunosuppressive drug dexamethasone

The immune response can be manipulated to suppress unwanted responses resulting from autoimmunity, allergy, and transplant rejection, and to stimulate protective responses against pathogens that largely elude the immune system (see immunization) or cancer.[125]

Immunosuppression

organ transplant.[126][127]

central obesity, hyperglycemia, and osteoporosis.[128] Their use is tightly controlled. Lower doses of anti-inflammatory drugs are often used in conjunction with cytotoxic or immunosuppressive drugs such as methotrexate or azathioprine
.

cyclosporin prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.[129]

Immunostimulation

Claims made by marketers of various products and alternative health providers, such as chiropractors, homeopaths, and acupuncturists to be able to stimulate or "boost" the immune system generally lack meaningful explanation and evidence of effectiveness.[130]

Vaccination

A child receiving drops of polio vaccine in her mouth
Polio vaccination in Egypt

Long-term active memory is acquired following infection by activation of B and T cells. Active immunity can also be generated artificially, through

specific immunity against that particular pathogen without causing disease associated with that organism.[131] This deliberate induction of an immune response is successful because it exploits the natural specificity of the immune system, as well as its inducibility. With infectious disease remaining one of the leading causes of death in the human population, vaccination represents the most effective manipulation of the immune system mankind has developed.[57][132]

Many vaccines are based on acellular components of micro-organisms, including harmless toxin components.[131] Since many antigens derived from acellular vaccines do not strongly induce the adaptive response, most bacterial vaccines are provided with additional adjuvants that activate the antigen-presenting cells of the innate immune system and maximize immunogenicity.[133]

Tumor immunology

Another important role of the immune system is to identify and eliminate

mouth, and throat,[136] while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells. One example is an enzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells (for example, melanocytes) into tumors called melanomas.[137][138] A third possible source of tumor antigens are proteins normally important for regulating cell growth and survival, that commonly mutate into cancer inducing molecules called oncogenes.[134][139][140]

See caption
Macrophages have identified a cancer cell (the large, spiky mass). Upon fusing with the cancer cell, the macrophages (smaller white cells) inject toxins that kill the tumor cell. Immunotherapy for the treatment of cancer is an active area of medical research.[141]

The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells.[138][142] Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to recognize the tumor cell as abnormal.[143] NK cells also kill tumorous cells in a similar way, especially if the tumor cells have fewer MHC class I molecules on their surface than normal; this is a common phenomenon with tumors.[144] Sometimes antibodies are generated against tumor cells allowing for their destruction by the complement system.[139]

Some tumors evade the immune system and go on to become cancers.

TGF-β, which suppresses the activity of macrophages and lymphocytes.[145][147] In addition, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells.[145][146]

Paradoxically, macrophages can promote tumor growth

tumor-necrosis factor alpha that nurture tumor development or promote stem-cell-like plasticity.[145] In addition, a combination of hypoxia in the tumor and a cytokine produced by macrophages induces tumor cells to decrease production of a protein that blocks metastasis and thereby assists spread of cancer cells.[145] Anti-tumor M1 macrophages are recruited in early phases to tumor development but are progressively differentiated to M2 with pro-tumor effect, an immunosuppressor switch. The hypoxia reduces the cytokine production for the anti-tumor response and progressively macrophages acquire pro-tumor M2 functions driven by the tumor microenvironment, including IL-4 and IL-10.[149] Cancer immunotherapy covers the medical ways to stimulate the immune system to attack cancer tumors.[150]

Predicting immunogenicity

Some drugs can cause a neutralizing immune response, meaning that the immune system produces

immunoinformatics.[155] Immunoproteomics is the study of large sets of proteins (proteomics) involved in the immune response.[156]

Evolution and other mechanisms

Evolution of the immune system

It is likely that a multicomponent, adaptive immune system arose with the first vertebrates, as invertebrates do not generate lymphocytes or an antibody-based humoral response.[157] Immune systems evolved in deuterostomes as shown in the cladogram.[157]

Deuterostomes
  
innate immunity
  

Many species, however, use mechanisms that appear to be precursors of these aspects of vertebrate immunity. Immune systems appear even in the structurally simplest forms of life, with bacteria using a unique defense mechanism, called the

archea) also possess acquired immunity, through a system that uses CRISPR sequences to retain fragments of the genomes of phage that they have come into contact with in the past, which allows them to block virus replication through a form of RNA interference.[159][160] Prokaryotes also possess other defense mechanisms.[161][162] Offensive elements of the immune systems are also present in unicellular eukaryotes, but studies of their roles in defense are few.[163]

Pattern recognition receptors are proteins used by nearly all organisms to identify molecules associated with pathogens. Antimicrobial peptides called defensins are an evolutionarily conserved component of the innate immune response found in all animals and plants, and represent the main form of invertebrate systemic immunity.[157] The complement system and phagocytic cells are also used by most forms of invertebrate life. Ribonucleases and the RNA interference pathway are conserved across all eukaryotes, and are thought to play a role in the immune response to viruses.[164]

Unlike animals, plants lack phagocytic cells, but many plant immune responses involve systemic chemical signals that are sent through a plant.

virus replication.[167]

Alternative adaptive immune system

immunoglobulins and T-cell receptors) exist only in jawed vertebrates. A distinct lymphocyte-derived molecule has been discovered in primitive jawless vertebrates, such as the lamprey and hagfish. These animals possess a large array of molecules called Variable lymphocyte receptors (VLRs) that, like the antigen receptors of jawed vertebrates, are produced from only a small number (one or two) of genes. These molecules are believed to bind pathogenic antigens in a similar way to antibodies, and with the same degree of specificity.[168]

Manipulation by pathogens

The success of any pathogen depends on its ability to elude host immune responses. Therefore, pathogens evolved several methods that allow them to successfully infect a host, while evading detection or destruction by the immune system.[169] Bacteria often overcome physical barriers by secreting enzymes that digest the barrier, for example, by using a type II secretion system.[170] Alternatively, using a type III secretion system, they may insert a hollow tube into the host cell, providing a direct route for proteins to move from the pathogen to the host. These proteins are often used to shut down host defenses.[171]

An evasion strategy used by several pathogens to avoid the innate immune system is to hide within the cells of their host (also called

intracellular pathogenesis). Here, a pathogen spends most of its life-cycle inside host cells, where it is shielded from direct contact with immune cells, antibodies and complement. Some examples of intracellular pathogens include viruses, the food poisoning bacterium Salmonella and the eukaryotic parasites that cause malaria (Plasmodium spp.) and leishmaniasis (Leishmania spp.). Other bacteria, such as Mycobacterium tuberculosis, live inside a protective capsule that prevents lysis by complement.[172] Many pathogens secrete compounds that diminish or misdirect the host's immune response.[169] Some bacteria form biofilms to protect themselves from the cells and proteins of the immune system. Such biofilms are present in many successful infections, such as the chronic Pseudomonas aeruginosa and Burkholderia cenocepacia infections characteristic of cystic fibrosis.[173] Other bacteria generate surface proteins that bind to antibodies, rendering them ineffective; examples include Streptococcus (protein G), Staphylococcus aureus (protein A), and Peptostreptococcus magnus (protein L).[174]

The mechanisms used to evade the adaptive immune system are more complicated. The simplest approach is to rapidly change non-essential epitopes (amino acids and/or sugars) on the surface of the pathogen, while keeping essential epitopes concealed. This is called antigenic variation. An example is HIV, which mutates rapidly, so the proteins on its viral envelope that are essential for entry into its host target cell are constantly changing. These frequent changes in antigens may explain the failures of vaccines directed at this virus.[175] The parasite Trypanosoma brucei uses a similar strategy, constantly switching one type of surface protein for another, allowing it to stay one step ahead of the antibody response.[176] Masking antigens with host molecules is another common strategy for avoiding detection by the immune system. In HIV, the envelope that covers the virion is formed from the outermost membrane of the host cell; such "self-cloaked" viruses make it difficult for the immune system to identify them as "non-self" structures.[177]

History of immunology

Portrait of an older, thin man with a beard wearing glasses and dressed in a suit and tie
Paul Ehrlich (1854–1915) was awarded a Nobel Prize in 1908 for his contributions to immunology.[178]

al-Razi (also known as Rhazes) wrote the first recorded theory of acquired immunity,[181][182] noting that a smallpox bout protected its survivors from future infections. Although he explained the immunity in terms of "excess moisture" being expelled from the blood—therefore preventing a second occurrence of the disease—this theory explained many observations about smallpox known during this time.[183]

These and other observations of acquired immunity were later exploited by

infectious disease.[185] Viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed.[186]

Immunology made a great advance towards the end of the 19th century, through rapid developments in the study of

Elie Metchnikoff.[178] In 1974, Niels Kaj Jerne developed the immune network theory; he shared a Nobel Prize in 1984 with Georges J. F. Köhler and César Milstein for theories related to the immune system.[188][189]

See also

References

Citations

  1. ^ Sompayrac 2019, p. 1.
  2. ^
    PMID 16261174
    .
  3. ^ Sompayrac 2019, p. 4.
  4. PMID 24148236
    .
  5. .
  6. ^ Sompayrac 2019, p. 11.
  7. ^ Sompayrac 2019, p. 146.
  8. ^ Alberts et al. 2002, sec. "Pathogens Cross Protective Barriers to Colonize the Host".
  9. PMID 11997295
    .
  10. .
  11. .
  12. .
  13. .
  14. .
  15. .
  16. .
  17. .
  18. .
  19. ^ a b Alberts et al. 2002, Chapter: "Innate Immunity".
  20. ^ Iriti 2019, p. xi.
  21. S2CID 42000671
    .
  22. .
  23. ^ Sompayrac 2019, p. 20.
  24. S2CID 20991617
    .
  25. .
  26. .
  27. .
  28. ^ Sompayrac 2019, pp. 1–4.
  29. ^ Alberts et al. 2002, sec. "Phagocytic Cells Seek, Engulf, and Destroy Pathogens".
  30. PMID 3910340
    .
  31. .
  32. PMID 11228151. Archived from the original
    on 31 March 2020. Retrieved 6 November 2009.
  33. S2CID 28520695. Archived from the original
    (PDF) on 31 March 2020.
  34. .
  35. ^ a b Stvrtinová, Jakubovský & Hulín 1995, Chapter: Inflammation and Fever.
  36. PMID 26162402
    .
  37. ^ .
  38. ^ Krishnaswamy, Ajitawi & Chi 2006, pp. 13–34.
  39. S2CID 260317790
    .
  40. .
  41. .
  42. ^ Bertok & Chow 2005, p. 17.
  43. ^ Rajalingam 2012, Chapter: Overview of the killer cell immunoglobulin-like receptor system.
  44. ^
    S2CID 9567407
    .
  45. ^ .
  46. ^ .
  47. ^ .
  48. ^ .
  49. .
  50. ^ .
  51. .
  52. ^ Bertok & Chow 2005, pp. 112–113.
  53. PMID 8834497
    .
  54. S2CID 24505041. Archived from the original
    (PDF) on 2 March 2019.
  55. .
  56. ^ Sompayrac 2019, p. 38.
  57. ^ a b c Janeway 2005.
  58. ^
    PMID 15976493
    .
  59. .
  60. ^ Janeway, Travers & Walport 2001, sec. 12-10.
  61. ^ Sompayrac 2019, pp. 5–6.
  62. ^ Sompayrac 2019, pp. 51–53.
  63. ^ Sompayrac 2019, pp. 7–8.
  64. PMID 10837060
    .
  65. ^ .
  66. .
  67. .
  68. ^ Sompayrac 2019, p. 8.
  69. PMID 12419850
    .
  70. ^ Alberts et al. 2002, Chapter. "Helper T Cells and Lymphocyte Activation".
  71. PMID 9597126
    .
  72. .
  73. ^ "Understanding the Immune System: How it Works" (PDF). National Institute of Allergy and Infectious Diseases (NIAID). Archived from the original (PDF) on 3 January 2007. Retrieved 1 January 2007.
  74. ^
    S2CID 6550357
    .
  75. .
  76. ^ Murphy & Weaver 2016, Chapter 10: The Humoral Immune Response.
  77. S2CID 31099552. Archived from the original
    (PDF) on 30 January 2021.
  78. .
  79. .
  80. ^ Sauls RS, McCausland C, Taylor BN. Histology, T-Cell Lymphocyte. In: StatPearls. StatPearls Publishing; 2023. Accessed November 15, 2023. http://www.ncbi.nlm.nih.gov/books/NBK535433/
  81. ^ Althwaiqeb SA, Bordoni B. Histology, B Cell Lymphocyte. In: StatPearls. StatPearls Publishing; 2023. Accessed November 15, 2023. http://www.ncbi.nlm.nih.gov/books/NBK560905/
  82. ^ Sompayrac 2019, p. 98.
  83. PMID 8262005
    .
  84. .
  85. .
  86. .
  87. .
  88. .
  89. ^ Wira, Crane-Godreau & Grant 2004, Chapter: Endocrine regulation of the mucosal immune system in the female reproductive tract.
  90. PMID 10655462
    .
  91. .
  92. .
  93. .
  94. ^ "Vitamin D - Fact Sheet for Health Professionals". Office of Dietary Supplements, US National Institutes of Health. 17 August 2021. Retrieved 31 March 2022.
  95. S2CID 58721779
    .
  96. .
  97. .
  98. .
  99. .
  100. .
  101. ^ .
  102. ^ "Can Better Sleep Mean Catching fewer Colds?". Archived from the original on 9 May 2014. Retrieved 28 April 2014.
  103. PMID 32728975
    .
  104. ^ .
  105. .
  106. .
  107. .
  108. .
  109. ^ Sompayrac 2019, pp. 120–24.
  110. ^ Sompayrac 2019, pp. 114–18.
  111. ^ Sompayrac 2019, pp. 111–14.
  112. PMID 17313487
    .
  113. ^ .
  114. .
  115. ^ Reece 2011, p. 967.
  116. PMID 21479529
    .
  117. .
  118. .
  119. .
  120. ^ Public Domain This article incorporates text from this source, which is in the public domain: "Hashimoto's disease". Office on Women's Health, U.S. Department of Health and Human Services. 12 June 2017. Archived from the original on 28 July 2017. Retrieved 17 July 2017.
  121. S2CID 37973054
    .
  122. .
  123. ^ "Handout on Health: Systemic Lupus Erythematosus". www.niams.nih.gov. February 2015. Archived from the original on 17 June 2016. Retrieved 12 June 2016.
  124. ^ a b c d Ghaffar A (2006). "Immunology – Chapter Seventeen: Hypersensitivity States". Microbiology and Immunology On-line. University of South Carolina School of Medicine. Retrieved 29 May 2016.
  125. ^ Sompayrac 2019, pp. 83–85.
  126. ^ Ciccone 2015, Chapter 37.
  127. ^
    PMID 16039869
    .
  128. .
  129. .
  130. ^ Hall H (July–August 2020). "How You Can Really Boost Your Immune System". Skeptical Inquirer. Amherst, New York: Center for Inquiry. Archived from the original on 21 January 2021. Retrieved 21 January 2021.
  131. ^ a b Reece 2011, p. 965.
  132. ^ Death and DALY estimates for 2002 by cause for WHO Member States. Archived 21 October 2008 at the Wayback Machine World Health Organization. Retrieved on 1 January 2007.
  133. S2CID 21346647
    .
  134. ^ .
  135. .
  136. .
  137. .
  138. ^ .
  139. ^ .
  140. .
  141. .
  142. .
  143. ^ .
  144. .
  145. ^ .
  146. ^ .
  147. .
  148. PMID 17695843. Archived from the original
    (PDF) on 16 July 2011.
  149. .
  150. .
  151. .
  152. .
  153. .
  154. .
  155. .
  156. .
  157. ^ .
  158. .
  159. .
  160. .
  161. .
  162. .
  163. .
  164. .
  165. ^ a b Schneider D. "Innate Immunity – Lecture 4: Plant immune responses" (PDF). Stanford University Department of Microbiology and Immunology. Retrieved 1 January 2007.
  166. PMID 17108957
    .
  167. .
  168. .
  169. ^ .
  170. .
  171. .
  172. .
  173. .
  174. S2CID 10322322. Archived from the original
    (PDF) on 2 March 2019.
  175. .
  176. .
  177. .
  178. ^ a b "The Nobel Prize in Physiology or Medicine 1908". The Nobel Prize. Retrieved 8 January 2007.
  179. PMID 9539938
    .
  180. .
  181. ^ Silverstein 1989, p. 6.
  182. ^ Silverstein 1989, p. 7.
  183. PMID 15812490
    .
  184. ^ The Nobel Prize in Physiology or Medicine 1905 Archived 10 December 2006 at the Wayback Machine Nobelprize.org Retrieved on 8 January 2009.
  185. ^ Major Walter Reed, Medical Corps, U.S. Army Walter Reed Army Medical Center. Retrieved on 8 January 2007.
  186. LCCN 68025143
    . history of humoral immunity.
  187. ^ "Niels K. Jerne". The Nobel Prize. Retrieved 27 November 2020.
  188. PMC 1326409
    .

General bibliography

Further reading

External links