Inbiology,immunity is the state of being insusceptible or resistant to a noxious agent or process, especially apathogen orinfectious disease. Immunity may occur naturally or be produced by prior exposure orimmunization.
Theimmune system hasinnate andadaptive components. Innate immunity is present in allmetazoans,[1] immune responses:inflammatory responses andphagocytosis.[2] The adaptive component, on the other hand, involves more advancedlymphatic cells that can distinguish between specific "non-self" substances in the presence of "self". The reaction to foreign substances is etymologically described asinflammation while the non-reaction to self substances is described as immunity. The two components of the immune system create a dynamic biological environment where "health" can be seen as a physical state where the self is immunologically spared, and what is foreign is inflammatorily and immunologically eliminated. "Disease" can arise when what is foreign cannot be eliminated or what is self is not spared.[3]
Innate immunity, also known as native immunity, is a semi-specific and widely distributed form of immunity. It is defined as the first line of defense against pathogens, representing a critical systemic response to preventinfection and maintain homeostasis, contributing to the activation of an adaptive immune response.[4] It does not adapt to specific external stimulus or a prior infection, but relies on genetically encoded recognition of particular patterns.[5]
Adaptive or acquired immunity is the active component of the host immune response, mediated by antigen-specificlymphocytes. Unlike the innate immunity, the acquired immunity is highly specific to a particular pathogen, including the development ofimmunological memory.[6] Like the innate system, the acquired system includes both humoral immunity components and cell-mediated immunity components.[citation needed]
Adaptive immunity can be acquired either 'naturally' (by infection) or 'artificially' (throughdeliberate actions such as vaccination). Adaptive immunity can also be classified as 'active' or 'passive'. Active immunity is acquired through the exposure to a pathogen, which triggers the production of antibodies by the immune system.[7] Passive immunity is acquired through the transfer of antibodies or activated T-cells derived from an immune host either artificially or through the placenta; it is short-lived, requiringbooster doses for continued immunity.
The diagram below summarizes these divisions of immunity. Adaptive immunity recognizes more diverse patterns. Unlike innate immunity it is associated with memory of the pathogen.[5]
For thousands of years mankind has been intrigued with the causes of disease and the concept of immunity. The prehistoric view was that disease was caused by supernatural forces, and that illness was a form oftheurgic punishment for "bad deeds" or "evil thoughts" visited upon the soul by the gods or by one's enemies.[8] In Classical Greek times,Hippocrates, who is regarded as the Father of Medicine, attributed diseases to an alteration or imbalance in one of thefour humors (blood, phlegm, yellow bile or black bile).[9] The first written descriptions of the concept of immunity may have been made by the AthenianThucydides who, in 430 BC, described that when the plague hitAthens: "the sick and the dying were tended by the pitying care of those who had recovered, because they knew the course of the disease and were themselves free from apprehensions. For no one was ever attacked a second time, or not with a fatal result".[10]
Active immunotherapy may have begun withMithridates VI of Pontus (120-63 BC)[11] who, to induce active immunity for snake venom, recommended using a method similar to moderntoxoidserum therapy, by drinking the blood of animals which fed on venomous snakes.[11] He is thought to have assumed that those animals acquired some detoxifying property, so that their blood would contain transformed components of the snake venom that could induce resistance to it instead of exerting a toxic effect. Mithridates reasoned that, by drinking the blood of these animals, he could acquire a similar resistance.[11] Fearing assassination by poison, he took daily sub-lethal doses of venom to build tolerance. He is also said to have sought to create a 'universal antidote' to protect him from all poisons.[9][12] For nearly 2000 years, poisons were thought to be theproximate cause of disease, and a complicated mixture of ingredients, calledMithridate, was used to cure poisoning during theRenaissance.[13][9] An updated version of this cure,Theriacum Andromachi, was used well into the 19th century. The term "immunes" is also found in the epic poem "Pharsalia" written around 60 BC by the poetMarcus Annaeus Lucanus to describe a North African tribe's resistance tosnake venom.[9]
The first clinical description of immunity which arose from a specific disease-causing organism is probablyA Treatise on Smallpox and Measles ("Kitab fi al-jadari wa-al-hasbah″, translated 1848[14][15]) written by theIslamic physicianAl-Razi in the 9th century. In the treatise, Al Razi describes the clinical presentation of smallpox and measles and goes on to indicate that exposure to these specific agents confers lasting immunity (although he does not use this term).[9]
Until the 19th century, themiasma theory was also widely accepted. The theory viewed diseases such ascholera or theBlack Plague as being caused by a miasma, a noxious form of "bad air".[8] If someone was exposed to the miasma in a swamp, in evening air, or breathing air in a sickroom or hospital ward, they could catch a disease. Since the 19th century, communicable diseases came to be viewed as being caused by germs/microbes.
The modern word "immunity" derives from theLatin immunis, meaning exemption from military service, tax payments or other public services.[10]
The first scientist who developed a full theory of immunity was Ilya Mechnikov[16] who revealedphagocytosis in 1882. WithLouis Pasteur'sgerm theory of disease, the fledgling science ofimmunology began to explain how bacteria caused disease, and how, following infection, the human body gained the ability to resist further infections.[10]
InEurope, the induction of active immunity emerged in an attempt to containsmallpox. Immunization has existed in various forms for at least a thousand years, without the terminology.[10] The earliest use of immunization is unknown, but, about 1000 AD, theChinese began practicing a form of immunization by drying and inhaling powders derived from the crusts of smallpox lesions.[10] Around the 15th century inIndia, theOttoman Empire, andeast Africa, the practice ofinoculation (poking the skin with powdered material derived from smallpox crusts) was quite common.[10] This practice was first introduced into the west in 1721 byLady Mary Wortley Montagu.[10] In 1798,Edward Jenner introduced the far safer method of deliberate infection withcowpox virus, (smallpox vaccine), which caused a mild infection that also induced immunity to smallpox. By 1800, the procedure was referred to asvaccination. To avoid confusion, smallpox inoculation was increasingly referred to asvariolation, and it became common practice to use this term without regard for chronology. The success and general acceptance of Jenner's procedure would later drive the general nature of vaccination developed by Pasteur and others towards the end of the 19th century.[9] In 1891, Pasteur widened the definition ofvaccine in honour of Jenner, and it then became essential to qualify the term by referring topolio vaccine,measles vaccine etc.
Passive immunity is the immunity acquired by the transfer of ready-madeantibodies from one individual to another. Passive immunity can occur naturally, such as when maternal antibodies are transferred to the foetus through the placenta, and can also be induced artificially, when high levels ofhuman (orhorse) antibodies specific for apathogen ortoxin are transferred to non-immune individuals. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing orimmunosuppressive diseases.[17] Passive immunity provides immediate protection, but the body does not develop memory, therefore the patient is at risk of being infected by the same pathogen later.[18]
Afetus naturally acquires passive immunity from its mother during pregnancy. Maternal passive immunity isantibody-mediated immunity. The mother's antibodies (MatAb) are passed through theplacenta to the fetus by anFcRn receptor on placental cells. This occurs around the third month ofgestation. IgG is the only antibodyisotype that can pass through the placenta.
Passive immunity is also provided through the transfer ofIgA antibodies found inbreast milk that are transferred to the gut of a nursing infant, protecting against bacterial infections, until the newborn can synthesize its antibodies.Colostrum present in mothers milk is an example of passive immunity.[18]
One of the first bottles ofdiphtheria antitoxin produced (dated 1895)
Artificially acquired passive immunity is a short-term immunization induced by the transfer of antibodies, which can be administered in several forms; as human or animal blood plasma, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, and in the form ofmonoclonal antibodies (MAb). Passive transfer is usedprophylactically in the case ofimmunodeficiency diseases, such ashypogammaglobulinemia.[19] It is also used in the treatment of several types of acute infection, and to treatpoisoning.[17] Immunity derived from passive immunization lasts for only a short period of time, and there is also a potential risk forhypersensitivity reactions, andserum sickness, especially fromgamma globulin of non-human origin.[18]
The artificial induction of passive immunity has been used for over a century to treat infectious disease, and before the advent ofantibiotics, was often the only specific treatment for certain infections. Immunoglobulin therapy continued to be a first line therapy in the treatment of severerespiratory diseases until the 1930s, even aftersulfonamide lot antibiotics were introduced.[19]
Passive or "adoptive transfer" of cell-mediated immunity, is conferred by the transfer of "sensitized" or activated T-cells from one individual into another. It is rarely used in humans because it requireshistocompatible (matched) donors, which are often difficult to find. In unmatched donors this type of transfer carries severe risks ofgraft versus host disease.[17] It has, however, been used to treat certain diseases including some types ofcancer andimmunodeficiency. This type of transfer differs from abone marrow transplant, in which (undifferentiated)hematopoietic stem cells are transferred.[citation needed]
The time course of an immune response. Due to the formation ofimmunological memory, reinfection at later time points leads to a rapid increase in antibody production and effector T cell activity. These later infections can be mild or even unapparent.
WhenB cells andT cells are activated by a pathogen, memory B-cells and T- cells develop, and the primary immune response results. Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and can mount a strong secondary response if the pathogen is detected again. The primary and secondary responses were first described in 1921 by English immunologist Alexander Glenny[20] although the mechanism involved was not discovered until later. This type of immunity is both active and adaptive because the body's immune system prepares itself for future challenges. Active immunity often involves both the cell-mediated and humoral aspects of immunity as well as input from theinnate immune system.
Naturally acquired active immunity occurs as the result of surviving an infection. When a person is exposed to a live pathogen and develops a primaryimmune response, this leads to immunological memory.[17] Many disorders of immune system function can affect the formation of active immunity, such asimmunodeficiency[21] (both acquired and congenital forms) andimmunosuppression.
Artificially acquired active immunity can be induced by avaccine, a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease.[17] The term vaccination was coined by Richard Dunning, a colleague ofEdward Jenner, and adapted byLouis Pasteur for his pioneering work in vaccination. The method Pasteur used entailed treating the infectious agents for those diseases, so they lost the ability to cause serious disease. Pasteur adopted the name vaccine as a generic term in honor of Jenner's discovery, which Pasteur's work built upon.
Poster from before the 1979 eradication of smallpox, promoting vaccination
In 1807,Bavaria became the first group to require their military recruits to be vaccinated against smallpox, as the spread of smallpox was linked to combat.[22] Subsequently, the practice of vaccination would increase with the spread of war.
Inactivated vaccines are composed of micro-organisms that have been killed with chemicals and/or heat and are no longer infectious. Examples are vaccines againstflu,cholera,plague, andhepatitis A. Most vaccines of this type are likely to require booster shots.
Live,attenuated vaccines are composed of micro-organisms that have been cultivated under conditions which disable their ability to induce disease. These responses are more durable, however, they may require booster shots. Examples includeyellow fever,measles,rubella, andmumps.
Toxoids are inactivated toxic compounds from micro-organisms in cases where these (rather than the micro-organism itself) cause illness, used prior to an encounter with the toxin of the micro-organism. Examples of toxoid-based vaccines includetetanus anddiphtheria.
In addition, there are some newer types of vaccines in use:
Outer Membrane Vesicle (OMV) vaccines contain the outer membrane of a bacterium without any of its internal components or genetic material. Thus, ideally, they stimulate an immune response effective against the original bacteria without the risk of an infection.[25]
Most vaccines are given byhypodermic orintramuscular injection as they are not absorbed reliably through the gut. Live attenuatedpolio and sometyphoid andcholera vaccines are givenorally in order to produce immunity based in thebowel.
Hybrid immunity is the combination of natural immunity and artificial immunity. Studies of hybrid-immune people found that their blood was better able to neutralize the Beta and other variants ofSARS-CoV-2 than never-infected, vaccinated people.[30] Moreover, on 29 October 2021, theCenters for Disease Control and Prevention (CDC) concluded that "Multiple studies in different settings have consistently shown that infection with SARS-CoV-2 and vaccination each result in a low risk of subsequent infection with antigenically similar variants for at least 6 months. Numerous immunologic studies and a growing number of epidemiologic studies have shown that vaccinating previously infected individuals significantly enhances their immune response and effectively reduces the risk of subsequent infection, including in the setting of increased circulation of more infectious variants. ..."[31]
Immunity is determined genetically.Genomes in humans andanimals encode theantibodies and numerous other immune response genes. While many of these genes are generally required for active and passive immune responses (see sections above), there are also manygenes that appear to be required for very specific immune responses. For instance,Tumor Necrosis Factor (TNF) is required for defense oftuberculosis in humans. Individuals with genetic defects in TNF may get recurrent and life-threatening infections with tuberculosis bacteria (Mycobacterium tuberculosis) but are otherwise healthy. They also seem to respond to other infections more or less normally. The condition is therefore calledMendelian susceptibility to mycobacterial disease (MSMD) and variants of it can be caused by other genes related tointerferon production or signaling (e.g. by mutations in the genesIFNG,IL12B,IL12RB1,IL12RB2,IL23R,ISG15,MCTS1,RORC,TBX21,TYK2,CYBB,JAK1,IFNGR1,IFNGR2,STAT1,USP18,IRF1,IRF8,NEMO,SPPL2A).[32]
^Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Innate Immunity. Available from:https://www.ncbi.nlm.nih.gov/books/NBK26846/
^Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Glossary. Available from:https://www.ncbi.nlm.nih.gov/books/NBK10759/
^"Immunity types".cdc.gov. Centers for Disease Control and Prevention (CDC). 2 November 2021.
