Search This Blog

Tuesday, May 12, 2020

Quarantine

From Wikipedia, the free encyclopedia
US President Nixon greeting the Apollo 11 astronauts in NASA's mobile quarantine facility
 
Signal flag "Lima", called the "Yellow Jack", which when flown in harbour means the ship is under quarantine
 
A quarantine is a restriction on the movement of people and goods which is intended to prevent the spread of disease or pests. It is often used in connection to disease and illness, preventing the movement of those who may have been exposed to a communicable disease, but do not have a confirmed medical diagnosis. It is distinct from medical isolation, in which those confirmed to be infected with a communicable disease are isolated from the healthy population. Quarantine considerations are often one aspect of border control.

The concept of quarantine has been known since biblical times, and is known to have been practised through history in various places. Notable quarantines in modern history include that of the village of Eyam in 1665 during the bubonic plague outbreak in England; East Samoa during the 1918 flu pandemic; the 1972 Yugoslav smallpox outbreak, and extensive quarantines applied throughout the world during the COVID-19 pandemic.

Ethical and practical considerations need to be considered when applying quarantine to people. Practice differs from country to country. In some countries, quarantine is just one of many measures governed by legislation relating to the broader concept of biosecurity; for example Australian biosecurity is governed by the single overarching Biosecurity Act 2015.

Etymology and terminology

The word quarantine comes from quarantena, meaning "forty days", used in the 14th–15th-centuries Venetian language and designating the period that all ships were required to be isolated before passengers and crew could go ashore during the Black Death plague epidemic; it followed the trentino, or thirty-day isolation period, first imposed in 1347 in the Republic of Ragusa, Dalmatia (modern Dubrovnik in Croatia).

Merriam-Webster gives various meanings to the noun form, including "a period of 40 days", several relating to ships, "a state of enforced isolation", and as "a restriction on the movement of people and goods which is intended to prevent the spread of disease or pests". The word is also used as a verb.

Quarantine is distinct from medical isolation, in which those confirmed to be infected with a communicable disease are isolated from the healthy population.

Quarantine may be used interchangeably with cordon sanitaire, and although the terms are related, cordon sanitaire refers to the restriction of movement of people into or out of a defined geographic area, such as a community, in order to prevent an infection from spreading.

History

Ancient

An early mention of isolation occurs in the Biblical book of Leviticus, written in the seventh century BC or perhaps earlier, which describes the procedure for separating out infected people to prevent spread of disease under the Mosaic Law:
"If the shiny spot on the skin is white but does not appear to be more than skin deep and the hair in it has not turned white, the priest is to isolate the affected person for seven days. On the seventh day the priest is to examine him, and if he sees that the sore is unchanged and has not spread in the skin, he is to isolate him for another seven days."

Medieval Islamic world

The Islamic prophet Muhammad advised quarantine: "Those with contagious diseases should be kept away from those who are healthy." Ibn Sina also recommended quarantine for patients with infectious diseases, especially tuberculosis.

The mandatory hospital quarantine of special groups of patients, including those with leprosy, started early in Islamic history. Between 706 and 707 the sixth Umayyad caliph Al-Walid I built the first hospital in Damascus and issued an order to isolate those infected with leprosy from other patients in the hospital. The practice of mandatory quarantine of leprosy in general hospitals continued until the year 1431, when the Ottomans built a leprosy hospital in Edirne. Incidents of quarantine occurred throughout the Muslim world, with evidence of voluntary community quarantine in some of these reported incidents. The first documented involuntary community quarantine was established by the Ottoman quarantine reform in 1838.

Medieval Europe

The word "quarantine" originates from quarantena, the Venetian language form, meaning "forty days". This is due to the 40-day isolation of ships and people practised as a measure of disease prevention related to the plague. Between 1348 and 1359, the Black Death wiped out an estimated 30% of Europe's population, and a significant percentage of Asia's population. Such a disaster led governments to establish measures of containment to handle recurrent epidemics. A document from 1377 states that before entering the city-state of Ragusa in Dalmatia (modern Dubrovnik in Croatia), newcomers had to spend 30 days (a trentine) in a restricted place (originally nearby islands) waiting to see whether the symptoms of Black Death would develop. In 1448 the Venetian Senate prolonged the waiting period to 40 days, thus giving birth to the term "quarantine". The forty-day quarantine proved to be an effective formula for handling outbreaks of the plague. Dubrovnik was the first city in Europe to set up quarantine sites such as the Lazzarettos of Dubrovnik where arriving ship personnel were held for up to 40 days. According to current estimates, the bubonic plague had a 37-day period from infection to death; therefore, the European quarantines would have been highly successful in determining the health of crews from potential trading and supply ships.

Other diseases lent themselves to the practice of quarantine before and after the devastation of the plague. Those afflicted with leprosy were historically isolated long-term from society, and attempts were made to check the spread of syphilis in northern Europe after 1492, the advent of yellow fever in Spain at the beginning of the 19th century, and the arrival of Asiatic cholera in 1831.

Venice took the lead in measures to check the spread of plague, having appointed three guardians of public health in the first years of the Black Death (1348). The next record of preventive measures comes from Reggio/Modena in 1374. Venice founded the first lazaret (on a small island adjoining the city) in 1403. In 1467 Genoa followed the example of Venice, and in 1476 the old leper hospital of Marseille was converted into a plague hospital. The great lazaret of Marseille, perhaps the most complete of its kind, was founded in 1526 on the island of Pomègues. The practice at all the Mediterranean lazarets did not differ from the English procedure in the Levantine and North African trade. On the arrival of cholera in 1831 some new lazarets were set up at western ports, notably a very extensive establishment near Bordeaux, afterwards turned to another use.

Modern history

The quarantine ship Rhin, at large in Sheerness. Source: National Maritime Museum of Greenwich, London
 
Epidemics of yellow fever ravaged urban communities in North America throughout the late-eighteenth and early-nineteenth centuries, the best-known examples being the 1793 Philadelphia yellow fever epidemic and outbreaks in Georgia (1856) and Florida (1888). Cholera and smallpox epidemics continued throughout the nineteenth century, and plague epidemics affected Honolulu and San Francisco from 1899 until 1901. State governments generally relied on the cordon sanitaire as a geographic quarantine measure to control the movement of people into and out of affected communities. During the 1918 influenza pandemic, some communities instituted protective sequestration (sometimes referred to as "reverse quarantine") to keep the infected from introducing influenza into healthy populations.

Isolating a village in Romania whose inhabitants believe that doctors poison those suspected of cholera (1911)
 
By the middle of the 19th century, the Ottoman Empire had established quarantine stations, including in Anatolia and the Balkans. For example, at the port of Izmir, all ships and their cargo would be inspected and those suspected of carrying the plague would be towed to separate docks and their personnel housed in separate buildings for a determined period of time. In Thessaly, along the Greek-Turkish border, all travellers entering and exiting the Ottoman Empire would be quarantined for 9–15 days. Upon appearance of the plague, the quarantine stations would be militarised and the Ottoman army would be involved in border control and disease monitoring.

International conventions 1852–1927

Since 1852 several conferences were held involving European powers, with a view to uniform action in keeping out infection from the East and preventing its spread within Europe. All but that of 1897 were concerned with cholera. No result came of those at Paris (1852), Constantinople (1866), Vienna (1874), and Rome (1885), but each of the subsequent ones doctrine of constructive infection of a ship as coming from a scheduled port, and an approximation to the principles advocated by Great Britain for many years. The principal countries which retained the old system at the time were Spain, Portugal, Turkey, Greece and Russia (the British possessions at the time, Gibraltar, Malta and Cyprus, being under the same influence). The aim of each international sanitary convention had been to bind the governments to a uniform minimum of preventive action, with further restrictions permissible to individual countries. The minimum specified by international conventions was very nearly the same as the British practice, which had been in turn adapted to continental opinion in the matter of the importation of rags.




The Venice convention of 30 January 1892 dealt with cholera by the Suez Canal route; that of Dresden of 15 April 1893, with cholera within European countries; that of Paris of 3 April 1894, with cholera by the pilgrim traffic; and that of Venice, on 19 March 1897, was in connection with the outbreak of plague in the East, and the conference met to settle on an international basis the steps to be taken to prevent, if possible, its spread into Europe. An additional convention was signed in Paris on 3 December 1903.


A multilateral international sanitary convention was concluded at Paris on 17 January 1912. This convention was most comprehensive and was designated to replace all previous conventions on that matter. It was signed by 40 countries, and consisted of 160 articles. Ratifications by 16 of the signatories were exchanged in Paris on 7 October 1920. Another multilateral convention was signed in Paris on 21 June 1926, to replace that of 1912. It was signed by 58 countries worldwide, and consisted of 172 articles.

In Latin America, a series of regional sanitary conventions were concluded. Such a convention was concluded in Rio de Janeiro on 12 June 1904. A sanitary convention between the governments of Argentina, Brazil, Paraguay and Uruguay was concluded in Montevideo on 21 April 1914. The convention covers cases of Asiatic cholera, oriental plague and yellow fever. It was ratified by the Uruguayan government on 13 October 1914, by the Paraguayan government on 27 September 1917 and by the Brazilian government on 18 January 1921.

Sanitary conventions were also concluded between European states. A Soviet-Latvian sanitary convention was signed on 24 June 1922, for which ratifications were exchanged on 18 October 1923. A bilateral sanitary convention was concluded between the governments of Latvia and Poland on 7 July 1922, for which ratifications were exchanged on 7 April 1925. Another was concluded between the governments of Germany and Poland in Dresden on 18 December 1922, and entered into effect on 15 February 1923. Another one was signed between the governments of Poland and Romania on 20 December 1922. Ratifications were exchanged on 11 July 1923. The Polish government also concluded such a convention with the Soviet government on 7 February 1923, for which ratifications were exchanged on 8 January 1924. A sanitary convention was also concluded between the governments of Poland and Czechoslovakia on 5 September 1925, for which ratifications were exchanged on 22 October 1926. A convention was signed between the governments of Germany and Latvia on 9 July 1926, for which ratifications were exchanged on 6 July 1927.

One of the first points to be dealt with in 1897 was to settle the incubation period for this disease, and the period to be adopted for administrative purposes. It was admitted that the incubation period was, as a rule, a comparatively short one, namely, of some three or four days. After much discussion ten days was accepted by a very large majority. The principle of disease notification was unanimously adopted. Each government had to notify to other governments on the existence of plague within their several jurisdictions, and at the same time state the measures of prevention which are being carried out to prevent its diffusion. The area deemed to be infected was limited to the actual district or village where the disease prevailed, and no locality was deemed to be infected merely because of the importation into it of a few cases of plague while there has been no diffusion of the malady. As regards the precautions to be taken on land frontiers, it was decided that during the prevalence of plague every country had the inherent right to close its land frontiers against traffic. As regards the Red Sea, it was decided after discussion that a healthy vessel could pass through the Suez Canal, and continue its voyage in the Mediterranean during the period of incubation of the disease the prevention of which is in question. It was also agreed that vessels passing through the Canal in quarantine might, subject to the use of the electric light, coal in quarantine at Port Said by night as well as by day, and that passengers might embark in quarantine at that port. Infected vessels, if these carry a doctor and are provided with a disinfecting stove, have a right to navigate the Canal, in quarantine, subject only to the landing of those who were suffering from plague.

21st century

In the 21st century, people suspected of carrying infectious diseases have been quarantined, as in the cases of Andrew Speaker (multi-drug-resistant tuberculosis, 2007) and Kaci Hickox (Ebola, 2014). Moving infected patients to isolation wards and home-based self-quarantine of people potentially exposed was the main way the Western African Ebola virus epidemic was ended in 2016; members of the 8th WHO Emergency Committee criticised international travel restrictions imposed during the epidemic as ineffective due to difficulty of enforcement, and counterproductive as they slowed down aid efforts. The People's Republic of China has employed mass quarantines – firstly of the city of Wuhan and subsequently of all of Hubei province (population 55.5 million) – in the COVID-19 pandemic. After few weeks, the Italian government imposed lockdowns in all the country (more than 60 million people) to stop the coronavirus pandemic. During the COVID-19 pandemic, India quarantined itself from the world for a period of one month.

Signals and flags

Signal flag "Quebec, " also called the "Yellow Jack" is a simple yellow flag that was historically used to signal quarantine (it stands for Q), but in modern use indicates the opposite, as a signal of a ship free of disease that requests boarding and inspection.

Plain yellow, green, and even black flags have been used to symbolise disease in both ships and ports, with the colour yellow having a longer historical precedent, as a colour of marking for houses of infection, previous to its use as a maritime marking colour for disease. The present flag used for the purpose is the "Lima" (L) flag, which is a mixture of yellow and black flags previously used. It is sometimes called the "yellow jack" but this was also a name for yellow fever, which probably derives its common name from the flag, not the colour of the victims (cholera ships also used a yellow flag). The plain yellow flag ("Quebec" or Q in international maritime signal flags) probably derives its letter symbol for its initial use in quarantine, but this flag in modern times indicates the opposite—a ship that 'requests free pratique', i.e. that declares itself free of quarantinable disease, and requests boarding and routine port inspection.

Ethical and practical considerations

The quarantining of people often raises questions of civil rights, especially in cases of long confinement or segregation from society, such as that of Mary Mallon (also known as Typhoid Mary), a typhoid fever carrier who was arrested and quarantined in 1907 and later spent the last 23 years and 7 months of her life in medical isolation at Riverside Hospital on North Brother Island.

The United Nations and the Siracusa Principles

Guidance on when and how human rights can be restricted to prevent the spread of infectious disease is found in The Siracusa Principles, a non-binding document developed by the Siracusa International Institute for Criminal Justice and Human Rights and adopted by the United Nations Economic and Social Council in 1984. The Siracusa Principles state that restrictions on human rights under the International Covenant on Civil and Political Rights must meet standards of legality, evidence-based necessity, proportionality, and gradualism, noting that public health can be used as grounds for limiting certain rights if the state needs to take measures 'aimed at preventing disease or injury or providing care for the sick and injured.' Limitations on rights (such as quarantine) must be 'strictly necessary,' meaning that they must:
  • respond to a pressing public or social need (health)
  • proportionately pursue a legitimate aim (prevent the spread of infectious disease)
  • be the least restrictive means required for achieving the purpose of the limitation
  • be provided for and carried out in accordance with the law
  • be neither arbitrary nor discriminatory
  • only limit rights that are within the jurisdiction of the state seeking to impose the limitation.
In addition, when quarantine is imposed, public health ethics specify that:
  • all restrictive actions must be well-supported by data and scientific evidence
  • all information must be made available to the public
  • all actions must be explained clearly to those whose rights are restricted and to the public
  • all actions must be subject to regular review and reconsideration.
Finally, the state is ethically obligated to offer certain guarantees:
  • Infected people will not be threatened or abused.
  • Basic needs such as food, water, medical care, and preventive care will be provided.
  • Communication with loved ones and with caretakers will be permitted.
  • Constraints on freedom will be applied equally, regardless of social considerations.
  • Patients will be compensated fairly for economic and material losses, including salary.[46]

Psychological impact

Quarantine can have negative psychological effects on those that are quarantined. These include post-traumatic stress, confusion and anger. According to a "Rapid Review" published in The Lancet in response to the COVID-19 pandemic, "Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable."

Short-term quarantines, e.g. for decontamination

Quarantine periods can be very short, such as in the case of a suspected anthrax attack, in which people are allowed to leave as soon as they shed their potentially contaminated garments and undergo a decontamination shower. For example, an article entitled "Daily News workers quarantined" describes a brief quarantine that lasted until people could be showered in a decontamination tent.

The February/March 2003 issue of HazMat Magazine suggests that people be "locked in a room until proper decon could be performed", in the event of "suspect anthrax".

Standard-Times senior correspondent Steve Urbon (14 February 2003) describes such temporary quarantine powers:
Civil rights activists in some cases have objected to people being rounded up, stripped and showered against their will. But Capt. Chmiel said local health authorities have "certain powers to quarantine people".
The purpose of such quarantine-for-decontamination is to prevent the spread of contamination and to contain the contamination such that others are not put at risk from a person fleeing a scene where contamination is suspect. It can also be used to limit exposure, as well as eliminate a vector.

New developments for quarantine include new concepts in quarantine vehicles such as the ambulance bus, mobile hospitals, and lockdown/invacuation (inverse evacuation) procedures, as well as docking stations for an ambulance bus to dock to a facility under lockdown.

Standard quarantine practices in different countries

Australia

Biosecurity in Australia is governed by the Biosecurity Act 2015. The Australian Quarantine and Inspection Service (AQIS) is responsible for border inspection of products brought into Australia, and assesses the risks the products might harm Australian environment. No person, goods and vessels are permitted into Australia without clearance from AQIS. Visitors are required to fill in the information card on arriving in Australia. Besides other risk factors, visitors are required to declare what food and products made of wood and other natural materials they have. Visitors who fail to do so may be subject to a fine of A$220, or may face criminal prosecution and be fined up to A$100,000 or imprisonment of up to 10 years.

Australia has very strict quarantine standards. Quarantine in northern Australia is especially important because of its proximity to South-East Asia and the Pacific, which have many pests and diseases not present in Australia. For this reason, the region from Cairns to Broome—including the Torres Strait—is the focus for quarantine activities that protect all Australians. As Australia has been geographically isolated from other major continents for millions of years, there is an endemically unique ecosystem free of several severe pests and diseases that are present in many parts of the world. If other products are brought inside along with pests and diseases, it would damage the ecosystem seriously and add millions of costs in the local agricultural businesses.

Canada

There are three quarantine Acts of Parliament in Canada: Quarantine Act (humans) and Health of Animals Act (animals) and Plant Protection Act (vegetations). The first legislation is enforced by the Canada Border Services Agency after a complete rewrite in 2005. The second and third legislations are enforced by the Canadian Food Inspection Agency. If a health emergency exists, the Governor in Council can prohibit importation of anything that it deems necessary under the Quarantine Act.

Under the Quarantine Act, all travellers must submit to screening and if they believe they might have come into contact with communicable diseases or vectors, they must disclose their whereabouts to a Border Services Officer. If the officer has reasonable grounds to believe that the traveller is or might have been infected with a communicable disease or refused to provide answers, a quarantine officer (QO) must be called and the person is to be isolated. If a person refuses to be isolated, any peace officer may arrest without warrant.




A QO who has reasonable grounds to believe that the traveller has or might have a communicable disease or is infested with vectors, after the medical examination of a traveller, can order him/her into treatment or measures to prevent the person from spreading the disease. QO can detain any traveller who refuses to comply with his/her orders or undergo health assessments as required by law. 




Under the Health of Animals Act and Plant Protection Act, inspectors can prohibit access to an infected area, dispose or treat any infected or suspected to be infected animals or plants. The Minister can order for compensation to be given if animals/plants were destroyed pursuant to these acts.
Each province also enacts its own quarantine/environmental health legislation.

Hong Kong

Under the Prevention and Control of Disease Ordinance (HK Laws. Chap 599), a health officer may seize articles they believe to be infectious or containing infectious agents. All travellers, if requested, must submit themselves to a health officer. Failure to do so is against the law and is subject to arrest and prosecution.

The law allows for a health officer who have reasonable grounds to detain, isolate, quarantine anyone or anything believed to be infected and to restrict any articles from leaving a designated quarantine area. He/she may also order the Civil Aviation Department to prohibit the landing or leaving, embarking or disembarking of an aircraft. This power also extends to land, sea or air crossings.

Under the same ordinance, any police officer, health officer, member of the Civil Aid Service, or member of the Auxiliary Medical Service can arrest a person who obstructs or escapes from detention.

United Kingdom

To reduce the risk of introducing rabies from continental Europe, the United Kingdom used to require that dogs, and most other animals introduced to the country, spend six months in quarantine at an HM Customs and Excise pound; this policy was abolished in 2000 in favour of a scheme generally known as Pet Passports, where animals can avoid quarantine if they have documentation showing they are up to date on their appropriate vaccinations.

British maritime quarantine rules 1711–1896

The plague had disappeared from England for more than thirty years before the practice of quarantine against it was definitely established by the Quarantine Act 1710 (9 Ann.) The first act was called for due to fears that the plague might be imported from Poland and the Baltic states. The second act of 1721 was due to the prevalence of plague at Marseille and other places in Provence, France. It was renewed in 1733 after a new outbreak in continental Europe, and again in 1743, due to an epidemic in Messina. In 1752 a rigorous quarantine clause was introduced into an act regulating trade with the Levant, and various arbitrary orders were issued during the next twenty years to meet the supposed danger of infection from the Baltic states. Although no plague cases ever came to England during that period, the restrictions on traffic became more stringent, and in 1788 a very strict Quarantine Act was passed, with provisions affecting cargoes in particular. The act was revised in 1801 and 1805, and in 1823–24 an elaborate inquiry was followed by an act making quarantine only at discretion of the privy council, which recognised yellow fever or other highly infectious diseases as calling for quarantine, along with plague. The threat of cholera in 1831 was the last occasion in England of the use of quarantine restrictions. Cholera affected every country in Europe despite all efforts to keep it out. When cholera returned to England in 1849, 1853 and 1865–66, no attempt was made to seal the ports. In 1847 the privy council ordered all arrivals with a clean bill of health from the Black Sea and the Levant to be admitted, provided there had been no case of plague during the voyage, and afterwards the practice of quarantine was discontinued.

After the passing of the first Quarantine Act (1710) the protective practices in England were haphazard and arbitrary. In 1721 two vessels carrying cotton goods from Cyprus, then affected by the plague, were ordered to be burned with their cargoes, the owners receiving an indemnity. By the clause in the Levant Trade Act of 1752, ships arriving in the United Kingdom with a "foul bill" (i.e. coming from a country where plague existed) had to return to the lazarets of Malta, Venice, Messina, Livorno, Genoa or Marseille, to complete a quarantine or to have their cargoes opened and aired. Since 1741 Stangate Creek (on the Medway) had been the quarantine station but it was available only for vessels with clean bills of health. In 1755 lazarets in the form of floating hulks were established in England for the first time, the cleansing of cargo (particularly by exposure to dews) having been done previously on the ship's deck. No medical inspections were conducted, but control was the responsibility of the Officers of Royal Customs and quarantine. In 1780, when plague was in Poland, even vessels with grain from the Baltic had to spend forty days in quarantine, and unpack and air their cargoes, but due to complaints mainly from Edinburgh and Leith, an exception was made for grain after that date. About 1788 an order of the council required every ship liable to quarantine to hoist a yellow flag in the daytime and show a light at the main topmast head at night, in case of meeting any vessel at sea, or upon arriving within four leagues of the coast of Great Britain or Ireland.

After 1800, ships from plague-affected countries (or with foul bills) were permitted to complete their quarantine in the Medway instead of at a Mediterranean port on the way, and an extensive lazaret was built on Chetney Hill near Chatham (although it was later demolished). The use of floating hulks as lazarets continued as before. In 1800 two ships with hides from Mogador in Morocco were ordered to be sunk with their cargoes at the Nore, the owners receiving an indemnity. Animal hides were suspected of harbouring infections, along with a long list of other items, and these had to be exposed on the ship's deck for twenty-one days or less (six days for each instalment of the cargo), and then transported to the lazaret, where they were opened and aired for another forty days. The whole detention of the vessel was from sixty to sixty-five days, including the time for reshipment of her cargo. Pilots had to pass fifteen days on board a convalescent ship. From 1846 onwards the quarantine establishments in the United Kingdom were gradually reduced, while the last vestige of the British quarantine law was removed by the Public Health Act of 1896, which repealed the Quarantine Act of 1825 (with dependent clauses of other acts), and transferred from the privy council to the Local Government Board the powers to deal with ships arriving infected with yellow fever or plague. The powers to deal with cholera ships had been already transferred by the Public Health Act 1875.

British regulations of 9 November 1896 applied to yellow fever, plague and cholera. Officers of the Customs, as well as of Royal Coast Guard and the Board of Trade (for signalling), were empowered to take the initial steps. They certified in writing the master of a supposedly infected ship, and detained the vessel provisionally for not more than twelve hours, giving notice meanwhile to the port sanitary authority. The medical officer of the port boarded the ship and examined every person in it. Every person found infected was taken to a hospital and quarantined under the orders of the medical officer, and the vessel remained under his orders. Every person suspected could be detained on board for 48 hours or removed to the hospital for a similar period. All others were free to land upon giving the addresses of their destinations to be sent to the respective local authorities, so that the dispersed passengers and crew could be kept individually under observation for a few days. The ship was then disinfected, dead bodies buried at sea, infected clothing, bedding, etc., destroyed or disinfected, and bilge-water and water-ballast pumped out at a suitable distance before the ship entered a dock or basin. Mail was subject to no detention. A stricken ship within 3 miles of the shore had to fly a yellow and black flag at the main mast from sunrise to sunset.

United States

In the United States, authority to quarantine people with infectious diseases is split between the state and federal governments. States (and tribal governments recognised by the federal government) have primary authority to quarantine people within their boundaries. Federal jurisdiction only applies to people moving across state or national borders, or people on federal property.

Federal rules

Communicable diseases for which apprehension, detention, or conditional release of people are authorised must be specified in Executive Orders of the President. As of 2014, these include Executive Orders 13295 13375, and 13674; the latest executive order specifies the following infectious diseases: cholera, diphtheria, infectious tuberculosis, plague, smallpox, yellow fever, viral haemorrhagic fevers (Lassa, Marburg, Ebola, Crimean-Congo, South American, and others not yet isolated or named), severe acute respiratory syndromes (SARS), and influenza from a novel or re-emergent source.

The Department of Health and Human Services is responsible for quarantine decisions, specifically the Centers for Disease Control and Prevention's Division of Global Migration and Quarantine. As of 21 March 2017, Centers for Disease Control and Prevention (CDC) regulations specify:
  • All commercial passenger flights must report deaths or illnesses to the CDC.
  • Individuals must apply for a travel permit if they are under a Federal quarantine, isolation, or conditional release order.
  • When an individual who is moving between U.S. states is "reasonably believed to be infected" with a quarantinable communicable disease in a "qualifying stage", the CDC may apprehend or examine that individual for potential infection.
  • This includes new regulatory authority permitting the CDC Director to prohibit the importation of animals or products that pose a threat to public health.
The rules:
  • Do not authorise compulsory medical testing, vaccination, or medical treatment without prior informed consent.
  • Require CDC to advise individuals subject to medical examinations that they will be conducted by an authorised health worker and with prior informed consent.
  • Include strong due process protections for individuals subject to public health orders, including a right to counsel for indigent individuals.
  • Limit to 72 hours the amount of time that an individual may be apprehended pending the issuance of a federal order for isolation, quarantine, or conditional release.

US quarantine facilities

The Division of Global Migration and Quarantine (DGMQ) of the US Center for Disease Control (CDC) operates small quarantine facilities at a number of US ports of entry. As of 2014, these included one land crossing (in El Paso, Texas) and 19 international airports. Besides the port of entry where it is located, each station is also responsible for quarantining potentially infected travellers entering through any ports of entry in its assigned region. These facilities are fairly small; each one is operated by a few staff members and capable of accommodating 1–2 travellers for a short observation period. Cost estimates for setting up a temporary larger facility, capable of accommodating 100 to 200 travellers for several weeks, have been published by the Airport Cooperative Research Program (ACRP) in 2008 of the Transportation Research Board.

US quarantine of imported goods

The United States puts immediate quarantines on imported products if a contagious disease is identified and can be traced back to a certain shipment or product. All imports will also be quarantined if the disease appears in other countries. According to Title 42 U.S.C. §§264 and 266, these statutes provide the Secretary of Health and Human Services peacetime and wartime authority to control the movement of people into and within the United States to prevent the spread of communicable disease.

History of quarantine laws in the US

Public Health Service Quarantine Station, New Orleans, Louisiana, 1957
 
Quarantine law began in Colonial America in 1663, when in an attempt to curb an outbreak of smallpox, the city of New York established a quarantine. In the 1730s, the city built a quarantine station on the Bedloe's Island. The Philadelphia Lazaretto was the first quarantine hospital in the United States, built in 1799, in Tinicum Township, Delaware County, Pennsylvania. There are similar national landmarks such as Swinburne Island and Angel Island. The Pest House in Concord, Massachusetts was used as early as 1752 to quarantine those suffering from cholera, tuberculosis and smallpox.

In early June 1832, during the cholera epidemic in New York, Governor Enos Throop called a special session of the Legislature for 21 June, to pass a Public Health Act by both Houses of the State Legislature. It included to a strict quarantine along the Upper and Lower New York-Canadian frontier. In addition, New York City Mayor Walter Browne established a quarantine against all peoples and products of Europe and Asia, which prohibited ships from approaching closer than 300 yards to the city, and all vehicles were ordered to stop 1.5 miles away.

The Immigrant Inspection Station on Ellis Island, built in 1892, is often mistakenly assumed to have been a quarantine station, however its marine hospital (Ellis Island Immigrant Hospital) only qualified as a contagious disease facility to handle less virulent diseases like measles, trachoma and less advanced stages of tuberculosis and diphtheria; those afflicted with smallpox, yellow fever, cholera, leprosy or typhoid fever, could neither be received nor treated there.

Mary Mallon was quarantined in 1907 under the Greater New York Charter, Sections 1169–1170, which permitted the New York City Board of Health to "remove to a proper place…any person sick with any contagious, pestilential or infectious disease."

During the 1918 flu pandemic, people were also quarantined. Most commonly suspect cases of infectious diseases are requested to voluntarily quarantine themselves, and Federal and local quarantine statutes only have been uncommonly invoked since then, including for a suspected smallpox case in 1963.

The 1944 Public Health Service Act "to apprehend, detain, and examine certain infected persons who are peculiarly likely to cause the interstate spread of disease" clearly established the federal government's quarantine authority for the first time. It gave the United States Public Health Service responsibility for preventing the introduction, transmission and spread of communicable diseases from foreign countries into the United States, and expanded quarantine authority to include incoming aircraft. The act states that "...any individual reasonably believed to be infected with a communicable disease in a qualifying stage and...if found to be infected, may be detained for such time and in such manner as may be reasonably necessary."

No federal quarantine orders were issued from 1963 until 2020, as American citizens were evacuated from China during the COVID-19 pandemic.

List of quarantine services in the world

Notable quarantines

Eyam village, 1665 (plague)

Eyam was a village in Britain that imposed protective sequestration on itself to stop the spread of the bubonic plague in 1665. The plague ran its course over 14 months and one account states that it killed at least 260 villagers. The church in Eyam has a record of 273 individuals who were victims of the plague.

Convict ship Surry, Sydney Harbour, 1814 (typhoid)

Quarantine of the convict ship Surry on the North Shore of Sydney Harbour in 1814, the first quarantine in Australia
 
On 28 July 1814, the convict ship Surry arrived in Sydney Harbour from England. Forty-six people had died of typhoid during the voyage, including 36 convicts, and the ship was placed in quarantine on the North Shore. Convicts were landed, and a camp was established in the immediate vicinity of what is now Jeffrey Street in Kirribilli. This was the first site in Australia to be used for quarantine purposes.

'Typhoid Mary' (US), 1907–1910 and 1915–1938

Mary Mallon was a cook who was found to be a carrier of Salmonella enterica subsp. enterica, the cause of typhoid fever, and was forcibly isolated from 1907 to 1910. At least 53 cases of the infection were traced to her, and three deaths. Subsequently she spent a further 23 years in isolation prior to her death in 1938. The presence of the bacteria in her gallbladder was confirmed on autopsy.

East Samoa, 1918 (flu pandemic)

During the 1918 flu pandemic, the then Governor of American Samoa, John Martin Poyer, imposed a full quarantine of the islands from all incoming ships, successfully achieving zero deaths within the territory. In contrast, the neighbouring New Zealand-controlled Western Samoa was among the hardest hit, with a 90% infection rate and over 20% of its adults dying from the disease. This failure by the New Zealand government to prevent and contain the Spanish Flu subsequently rekindled Samoan anti-colonial sentiments that led to its eventual independence.

Gruinard Island, 1942–1990 (anthrax)

In 1942, during World War II, British forces tested out their biological weapons program on Gruinard Island and infected it with anthrax. Subsequently a quarantine order was placed on the island. The quarantine was lifted in 1990, when the island was declared safe, and a flock of sheep was released onto the island.

Apollo series space explorers, 1969–1971

Between 24 July 1969 and 9 February 1971, the astronauts of Apollo 11, Apollo 12, and Apollo 14, were quarantined (in each case for a total of 21 days) after returning to Earth, initially where they were recovered and then being transferred to the Lunar Receiving Laboratory, to prevent possible interplanetary contamination by microorganisms from the Moon. All lunar samples were also held in the biosecure environment of the Lunar Receiving Laboratory for initial assay.

Yugoslavia, 1972 (smallpox)

The 1972 Yugoslav smallpox outbreak was the final outbreak of smallpox in Europe. The World Health Organization fought the outbreak with extensive quarantine, and the government instituted martial law.

Case of Kaci Hickox' return to US, 2014 (Ebola)

In 2014, Kaci Hickox, a Doctors Without Borders nurse from Maine, legally battled 21-day quarantines imposed by the states of New Jersey and Maine after returning home from treating Ebola patients in Sierra Leone. "Hickox was sequestered in a medical tent for days because New Jersey announced new Ebola regulations the day she arrived. She eventually was allowed to travel to Maine, where the state sought to impose a 'voluntary quarantine' before trying and failing to create a buffer between her and others. A state judge rejected attempts to restrict her movements, saying she posed no threat as long as she wasn't demonstrating any symptoms of Ebola. Hickox said health care professionals like those at the U.S. Centers for Disease Control and Prevention – not politicians like New Jersey Gov. Chris Christie and Maine Gov. Paul LePage – should be in charge of making decisions that are grounded in science, not fear."

COVID-19 pandemic

During the COVID-19 pandemic, multiple governmental actors enacted quarantines in an effort to curb the rapid spread of the virus. 

On 26 March, 1.7 billion people worldwide were under some form of lockdown, which increased to 2.6 billion people two days later—around a third of the world's population.

Hubei

In Hubei, the origin of the epidemic, a cordon sanitaire was imposed on Wuhan and other major cities in China, affecting around 500 million people, which is unprecedented in scale in human history, to limit the rate of spread of the disease. The 'lockdown' of Wuhan, and subsequently a wider-scale 'lockdown' throughout Hubei province, began on 23 January 2020. At this stage, the spread of the virus in mainland China was running at approximately 50% growth in cases per day. On 8 February, the daily rate of spread fell below 10%.

Italy

As the outbreak spread there, beginning 22 February 2020, a cordon sanitaire was imposed on a group of at least 10 different municipalities in Northern Italy, effectively quarantining more than 50,000 people. This followed a second day when the declared detected cases leapt enormously (the period from 21 to 23 February saw daily increases of 567%, 295% and 90% respectively). A week later the rate of increase of cases in Italy was significantly reduced (the period from 29 February to 4 March saw daily increases of 27%, 50%, 20%, 23% and 23%).

On 8 March 2020, a much wider region of Northern Italy was placed under quarantine restrictions, involving around 16 million people. On the next day, the quarantine was extended to the whole of Italy, effective on 10 March 2020, placing roughly 60 million people under quarantine.

A team of Chinese experts, together with some 31 tonnes of supplies, arrived in Rome on 13 March 2020 to help Italy fight the virus.

On 22 March 2020, Russia sent nine Ilyushin 76 planes with expert virologists, epidemiologists, medical equipment and pharmaceuticals in a humanitarian aid operation that Italian media dubbed "From Russia With Love".

Rest of Europe

Slovakia closed borders to non-residents because of the coronavirus pandemic.
 
As cases of the virus spread to and took hold in more European countries, many followed the earlier examples of China and Italy and began instituting policies of lockdown. Notable among these were Ireland (where schools have been closed for the rest of March and limits set on sizes of meetings), Spain (where a lockdown was announced on 14 March), Czech Republic, Norway, Denmark, Iceland, Poland, Turkey and France, while the United Kingdom noticeably lagged behind in adopting such measures.

As of 18 March, more than 250 million people are in lockdown across Europe.

Rest of the world

In the immediate context of the start of the pandemic in Wuhan, countries neighbouring or close to China adopted a cautious approach. For example, Sri Lanka, Macau, Hong Kong, Vietnam, Japan and South Korea had all imposed some degree of lockdown by 19 February. As countries across the world reported escalating case numbers and deaths, more and more countries began to announce travel restrictions and lockdowns. Africa and Latin America were relatively delayed in the spread of the virus, but even on these continents, countries began to impose travel bans and lockdowns. Brazil and Mexico began lockdowns in late February and much of the rest of Latin America followed suit in early March. Much of Africa was on lockdown by the start of April. Kenya, for example, blocked certain international flights and subsequently placed a ban on 'global' meetings.

As of 1 April, more than 280 million people, or about 86% of the population, are under some form of lockdown in the United States, 59 million people are in lockdown in South Africa, and 1.3 billion people are in lockdown in India.

Self quarantine

Self quarantine (or self-isolation) is a popular term that emerged during the COVID-19 pandemic, which spread to most countries in 2020. Citizens able to do so were encouraged to stay home to curb the spread of the disease.

Other uses

U.S. President John F. Kennedy euphemistically referred to the U.S. Navy's interdiction of shipping en route to Cuba during the Cuban Missile Crisis as a "quarantine" rather than a blockade, because a quarantine is a legal act in peacetime, whereas a blockade is defined as an act of aggression under the U.N. Charter.

In computer science, "quarantining" describes putting files infected by computer viruses into a special directory, so as to eliminate the threat they pose, without irreversibly deleting them.

The Spanish term for quarantine, (la) cuarentena, refers also to the period of postpartum confinement in which a new mother and her baby are sheltered from the outside world.

Adaptive immune system

From Wikipedia, the free encyclopedia
 
A scanning electron microscope image of a single human lymphocyte
 
The adaptive immune system, also referred as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminates pathogens by preventing their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates (the other being the innate immune system). 

Acquired immunity creates immunological memory after an initial response to a specific pathogen, and leads to an enhanced response to subsequent encounters with that pathogen. This process of acquired immunity is the basis of vaccination. Like the innate system, the acquired system includes both humoral immunity components and cell-mediated immunity components.





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".
 
Unlike the innate immune system, the acquired immune system is highly specific to a particular pathogen. Acquired immunity can also provide long-lasting protection; for example, someone who recovers from measles is now protected against measles for their lifetime. In other cases it does not provide lifetime protection; for example, chickenpox. The acquired system response destroys invading pathogens and any toxic molecules they produce. Sometimes the acquired system is unable to distinguish harmful from harmless foreign molecules; the effects of this may be hayfever, asthma or any other allergy

Antigens are any substances that elicit the acquired immune response (whether adaptive or maladaptive to the organism).

The cells that carry out the acquired immune response are white blood cells known as lymphocytes. Two main activities—antibody responses and cell mediated immune response—are also carried out by two different lymphocytes (B cells and T cells). 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.

In acquired immunity, pathogen-specific receptors are "acquired" during the lifetime of the organism (whereas in innate immunity pathogen-specific receptors are already encoded in the germline). The 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 autoimmunity).

The system is highly adaptable because of somatic hypermutation (a process of accelerated somatic mutations), and V(D)J recombination (an irreversible genetic recombination of antigen receptor gene segments). This mechanism allows a small number of genes 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.

A theoretical framework explaining the workings of the acquired immune system is provided by immune network theory. This theory, which builds on established concepts of clonal selection, is being applied in the search for an HIV vaccine.

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 Tonegawas'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

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

The cells of the acquired immune system are T and B lymphocytes; lymphocytes are a subset of leukocyte. B cells and T cells are the major types of lymphocytes. The human body has about 2 trillion lymphocytes, constituting 20–40% of white blood cells (WBCs); their total mass is about the same as the brain or liver. The peripheral blood contains 2% of circulating lymphocytes; the rest move within the tissues and lymphatic system.

B cells and T cells are derived from the same multipotent hematopoietic stem cells, and are morphologically indistinguishable from 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 progenitors migrate from the bone marrow to the thymus where they are called thymocytes and where they develop into T cells. In humans, approximately 1–2% of the lymphocyte pool recirculates each hour to optimize the opportunities for antigen-specific lymphocytes to find their specific antigen within the secondary lymphoid tissues. 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 (cells that have not matured), left the bone marrow or thymus, have entered the lymphatic system, but have yet to encounter their cognate antigen,
  • effector cells that have been activated by their cognate 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" 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

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.

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

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 cells or clear pathogens, but, in essence "manage" the immune response, by directing other cells to perform these tasks.




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.


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.

The Th1 response is characterized by the production of Interferon-gamma, which activates the bactericidal activities of macrophages, and induces B cells to make opsonizing (marking for phagocytosis) and complement-fixing antibodies, and leads to cell-mediated immunity. In general, Th1 responses are more effective against intracellular pathogens (viruses and bacteria that are inside host cells). 

The Th2 response is characterized by the release of Interleukin 5, which induces eosinophils in the clearance of parasites. Th2 also produce Interleukin 4, which facilitates B cell isotype switching. In general, Th2 responses are more effective against extracellular bacteria, parasites including helminths and toxins. 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. Regulatory T (Treg) cells, have been identified as important negative regulators of adaptive immunity as they limit and suppresses the immune system to control aberrant immune responses to self-antigens; an important mechanism in controlling the development of autoimmune diseases. Follicular helper T (Tfh) cells are another distinct population of effector CD4+ T cells that develop from naive T cells post-antigen activation. Tfh cells are specialized in helping B cell humoral immunity as they are uniquely capable of migrating to follicular B cells in secondary lymphoid organs and provide them positive paracrine signals to enable the generation and recall production of high-quality affinity-matured antibodies. Similar to Tregs, Tfh cells also play a role in immunological tolerance as an abnormal expansion of Tfh cell numbers can lead to unrestricted autoreactive antibody production causing severe systemic autoimmune disorders.

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.

Gamma delta T cells

Gamma delta T cells (γδ T cells) possess an alternative T cell receptor (TCR) as opposed to CD4+ and CD8+ αβ T cells and share characteristics of helper T cells, cytotoxic T cells and natural killer cells. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted natural killer T cells, γδ T cells exhibit characteristics that place them at the border between innate and acquired immunity. On one hand, γδ T cells may be considered a component of adaptive immunity in that they rearrange TCR genes via V(D)J recombination, which also produces junctional diversity, and develop a memory phenotype. On the other hand, however, the various subsets may also be considered part of the innate immune system where a restricted TCR or NK receptors may be used as a pattern recognition receptor. For example, according to this paradigm, large numbers of Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted intraepithelial Vδ1 T cells respond to stressed epithelial cells.

B lymphocytes and antibody production

The B lymphocyte activation pathway. B cells function to protect the host by producing antibodies that identify and neutralize foreign objects like bacteria and viruses.
 
B Cells are the major cells involved in the creation of antibodies that circulate in blood plasma and lymph, known as humoral immunity. Antibodies (also known as immunoglobulin, Ig), are large Y-shaped proteins used by the immune system to identify and neutralize foreign objects. In mammals, there are five types of antibody: IgA, IgD, IgE, IgG, and IgM, differing in biological properties; each has evolved to handle different kinds of antigens. Upon activation, B cells produce antibodies, each of which recognize a unique antigen, and neutralizing specific pathogens.

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, whereas B cells recognize antigens in their native form. Once a B cell encounters its cognate (or specific) antigen (and receives additional signals from a helper T cell (predominately Th2 type)), it further differentiates into an effector cell, known as a plasma cell.

Plasma cells are short-lived cells (2–3 days) that secrete antibodies. These antibodies bind to antigens, making them easier targets for phagocytes, and trigger the complement cascade. About 10% of plasma cells survive to become long-lived antigen-specific memory B cells. Already primed to produce specific antibodies, these cells can be called upon to respond quickly if the same pathogen re-infects the host, while the host experiences few, if any, symptoms.

Alternative systems

In jawless vertebrates

Primitive jawless vertebrates, such as the lamprey and hagfish, have an adaptive immune system that shows 3 different cell lineages, each sharing a common origin with B cells, αβ T cells, and innate-like γΔ T cells. Instead of the classical antibodies and T cell receptors, these animals possess a large array of molecules called variable lymphocyte receptors (VLRs for short) 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.

In insects

For a long time it was thought that insects and other invertebrates possess only innate immune system. However, in recent years some of the basic hallmarks of adaptive immunity have been discovered in insects. Those traits are immune memory and specificity. Although the hallmarks are present the mechanisms are different from those in vertebrates

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. 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. 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. Other experimental model based on red flour beetle also showed pathogen specific primed memory transfer into offspring from both mothers and fathers.

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. 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.

Other mechanisms supporting the specificity of insect immunity is RNA interference (RNAi). RNAi is a form of antiviral immunity with high specificity. It has several different pathways that all end with the virus being unable to replicate. One of the pathways is siRNA in which long double stranded RNA is cut into pieces that serve as templates for protein complex Ago2-RISC that finds and degrades complementary RNA of the virus. MiRNA pathway in cytoplasm binds to Ago1-RISC complex and functions as a template for viral RNA degradation. Last one is piRNA where small RNA binds to the Piwi protein family and controls transposones and other mobile elements. Despite the research the exact mechanisms responsible for immune priming and specificity in insects are not well described.

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.

Passive memory

Passive memory is usually short-term, lasting between a few days and several months. Newborn infants have had no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. In utero, maternal IgG is transported directly across the placenta, so that, at birth, human babies have high levels of antibodies, with the same range of antigen specificities as their mother. Breast milk contains antibodies (mainly IgA) that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies.

This is passive immunity because the fetus does not actually make any memory cells or antibodies: It only borrows them. Short-term passive immunity can also be transferred artificially from one individual to another via antibody-rich serum.

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. 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. Immunizations are successful because they utilize the immune system's natural specificity as well as its inducibility.

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.

Most viral vaccines are based on live attenuated viruses, whereas many bacterial vaccines are based on acellular components of microorganisms, including harmless toxin components. Many antigens derived from acellular vaccines do not strongly induce an adaptive response, and most bacterial vaccines require the addition of adjuvants that activate the antigen-presenting cells of the innate immune system to enhance immunogenicity.

Immunological diversity

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.
 
Most large molecules, including virtually all proteins and many polysaccharides, can serve as antigens. 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. 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.

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, 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. 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.

Myriad receptors are produced through a process known as clonal selection. 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. 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.

Note that the innate and acquired portions of the immune system work together, not in spite of each other. The acquired arm, B, and T cells couldn't function without the innate system' input. T cells are useless without antigen-presenting cells to activate them, and B cells are crippled 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 fetus (which is considered "non-self") from attack by the immune system, are particularly interesting. Although no comprehensive explanation has emerged to explain this mysterious, and often repeated, lack of rejection, two classical reasons may explain how the fetus is tolerated. The first is that the fetus occupies a portion of the body protected by a non-immunological barrier, the uterus, which the immune system does not routinely patrol. The second is that the fetus itself may promote local immunosuppression in the mother, perhaps by a process of active nutrient depletion. A more modern explanation for this induction of tolerance is that specific glycoproteins expressed in the uterus during pregnancy suppress the uterine immune response (see eu-FEDS). 

During pregnancy in viviparous mammals (all mammals except Monotremes), endogenous retroviruses (ERVs) are activated and produced in high quantities during the implantation of the embryo. They are currently known to possess immunosuppressive properties, suggesting a role in protecting the embryo from its mother's immune system. Also, viral fusion proteins cause the formation of the placental syncytium to limit exchange of migratory cells between the developing embryo and the body of the mother (something an epithelium can't do sufficiently, as certain blood cells specialize to insert themselves between adjacent epithelial cells). The immunodepressive action was the initial normal behavior of the virus, similar to HIV. The fusion proteins were a way to spread the infection to other cells by simply merging them with the infected one (HIV does this too). It is believed that the ancestors of modern viviparous mammals evolved after an infection by this virus, enabling the fetus to survive the immune system of the mother.

The human genome project found several thousand ERVs classified into 24 families.

Immune network theory

A theoretical framework explaining the workings of the acquired immune system is provided by immune network theory, based on interactions between idiotypes (unique molecular features of one clonotype, i.e. the unique set of antigenic determinants of the variable portion of an antibody) and 'anti-idiotypes' (antigen receptors that react with the idiotype as if it were a foreign antigen). This theory, which builds on the existing clonal selection hypothesis and since 1974 has been developed mainly by Niels Jerne and Geoffrey W. Hoffmann, is seen as being relevant to the understanding of the HIV pathogenesis and the search for an HIV vaccine.

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. Cytokines produced during innate immune responses are among the activators of adaptive immune responses. Antibodies exert additive or synergistic effects with mechanisms of innate immunity. Unstable HbS clusters Band-3, a major integral red cell protein; 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.

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.

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, 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.

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 cartilaginous fishes. Lymphocyte receptors, Ig and TCR, are found in all jawed vertebrates. The most ancient Ig class, IgM, is membrane-bound and then secreted upon stimulation of cartilaginous fish B cells. Another isotype, shark IgW, is related to mammalian IgD. TCRs, both α/β and γ/δ, are found in all animals from gnathostomes to mammals. The organization of gene segments that undergo gene rearrangement differs in cartilaginous fishes, which have a cluster form as compared to the translocon form in bony fish to mammals. Like TCR and Ig, the MHC is found only in jawed vertebrates. Genes involved in antigen processing and presentation, as well as the class I and class II genes, are closely linked within the MHC of almost all studied species.

Lymphoid cells can be identified in some pre-vertebrate deuterostomes (i.e., sea urchins). These bind antigen with pattern recognition receptors (PRRs) of the innate immune system. In jawless fishes, two subsets of lymphocytes use variable lymphocyte receptors (VLRs) for antigen binding. Diversity is generated by a cytosine deaminase-mediated rearrangement of LRR-based DNA segments. There is no evidence for the recombination-activating genes (RAGs) that rearrange Ig and TCR gene segments in jawed vertebrates. 

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 RAG transposon (possibly of viral origin) and two whole genome duplications. Though the molecules of the AIS are well-conserved, they are also rapidly evolving. Yet, a comparative approach finds that many features are quite uniform across taxa. All the major features of the AIS arose early and quickly. Jawless fishes have a different AIS that relies on gene rearrangement to generate diverse immune receptors with a functional dichotomy that parallels Ig and TCR molecules. The innate immune system, which has an important role in AIS activation, is the most important defense system of invertebrates and plants.

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 crosses 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.

Cooperative

From Wikipedia, the free encyclopedia ...