Swine influenza is an infection caused by any of several types of swine influenza viruses . Swine influenza virus ( SIV ) or swine-origin influenza virus ( S-OIV ) refers to any strain of the influenza family of viruses that is endemic in pigs . As of 2009, identified SIV strains include influenza C and the subtypes of influenza A known as H1N1 , H1N2 , H2N1, H3N1 , H3N2 , and H2N3 .
171-407: The swine influenza virus is common throughout pig populations worldwide. Transmission of the virus from pigs to humans is rare and does not always lead to human illness, often resulting only in the production of antibodies in the blood. If transmission causes human illness, it is called a zoonotic swine flu. People with regular exposure to pigs are at increased risk of swine flu infections. Around
342-448: A public health emergency , and several U.S. states then indicated that they may follow suit. Secretary of Homeland Security Janet Napolitano noted that this declaration was standard operating procedure, which was also done for the 2009 presidential inauguration and for flooding. After many days of deliberation the WHO declared that the current influenza had become a true pandemic, raising
513-472: A "sandwich" shape, the immunoglobulin fold , held together by a disulfide bond. Secreted antibodies can occur as a single Y-shaped unit, a monomer . However, some antibody classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six units). IgG can also form hexamers, though no J chain
684-465: A 30 percent spike in flu visits. As pediatric cases were increasing, the Dept. of Health and Human Services released 300,000 courses of children's liquid Tamiflu from the national pandemic stockpile in late September, with the first batches sent to Texas and Colorado. In late September, the disease centers reported that 936 had died of flu symptoms or of flu-associated pneumonia since August 30, when it began
855-520: A B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a " naive B lymphocyte ." The naive B lymphocyte expresses both surface IgM and IgD. The co-expression of both of these immunoglobulin isotypes renders the B cell ready to respond to antigen. B cell activation follows engagement of
1026-600: A Y shape. In humans and most other mammals , an antibody unit consists of four polypeptide chains ; two identical heavy chains and two identical light chains connected by disulfide bonds . Each chain is a series of domains : somewhat similar sequences of about 110 amino acids each. These domains are usually represented in simplified schematics as rectangles. Light chains consist of one variable domain V L and one constant domain C L , while heavy chains contain one variable domain V H and three to four constant domains C H 1, C H 2, ... Structurally an antibody
1197-441: A distinct epitope of an antigen. Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited by the size of the human genome. Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes. The chromosomal region that encodes an antibody
1368-542: A given microbe – that is, the ability of the microbe to enter the body and begin to replicate (not necessarily to cause disease) – depends on sustained production of large quantities of antibodies, meaning that effective vaccines ideally elicit persistent high levels of antibody, which relies on long-lived plasma cells. At the same time, many microbes of medical importance have the ability to mutate to escape antibodies elicited by prior infections, and long-lived plasma cells cannot undergo affinity maturation or class switching. This
1539-425: A hospital focuses on controlling fevers, relieving pain and maintaining fluid balance, as well as identifying and treating any secondary infections or other medical problems. The U.S. Centers for Disease Control and Prevention recommends the use of oseltamivir (Tamiflu) or zanamivir (Relenza) for the treatment and/or prevention of infection with swine influenza viruses; however, the majority of people infected with
1710-408: A huge number of antibodies, each with different paratopes , and thus different antigen specificities. The rearrangement of several subgenes (i.e. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells. RAG proteins play an important role with V(D)J recombination in cutting DNA at a particular region. Without
1881-627: A large study in China, reported in the New England Journal of Medicine , covering close to 100 million doses of H1N1 flu vaccine, found only 11 cases of GBS, which is lower than the normal rate of the disease in China: "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination." In September 1988, a swine flu virus killed one woman and infected others. A 32-year-old woman, Barbara Ann Wieners,
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#17333735056992052-1214: A link exists is still not clear, this syndrome may be a side effect of influenza vaccines. As a result, Di Justo writes, "the public refused to trust a government-operated health program that killed old people and crippled young people." In total, 48,161,019 Americans, or just over 22% of the population, had been immunized by the time the National Influenza Immunization Program was effectively halted on December 16, 1976. Overall, there were 1098 cases of GBS recorded nationwide by CDC surveillance, 532 of which occurred after vaccination and 543 before vaccination. About one to two cases per 100,000 people of GBS occur every year, whether or not people have been vaccinated. The vaccination program seems to have increased this normal risk of developing GBS by about to one extra case per 100,000 vaccinations. Recompensation charges were filed for over 4,000 cases of severe vaccination damage, including 25 deaths, totaling US$ 3.5 billion, by 1979. The CDC stated most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations,
2223-575: A majority of H3N2 viruses. The United States Department of Agriculture researchers say while pig vaccination keeps pigs from getting sick, it does not block infection or shedding of the virus. Facility management includes using disinfectants and ambient temperature to control viruses in the environment. They are unlikely to survive outside living cells for more than two weeks, except in cold (but above freezing) conditions, and are readily inactivated by disinfectants. Herd management includes not adding pigs carrying influenza to herds that have not been exposed to
2394-440: A manifestation of immunological memory. In the course of an immune response, B cells can progressively differentiate into antibody-secreting cells or into memory B cells. Antibody-secreting cells comprise plasmablasts and plasma cells , which differ mainly in the degree to which they secrete antibody, their lifespan, metabolic adaptations, and surface markers. Plasmablasts are rapidly proliferating, short-lived cells produced in
2565-400: A mast cell, triggering its degranulation : the release of molecules stored in its granules. Binds to allergens and triggers histamine release from mast cells and basophils , and is involved in allergy . Humans and other animals evolved IgE to protect against parasitic worms , though in the present, IgE is primarily related to allergies and asthma. Although The antibody isotype of
2736-525: A naval research facility studying a special diagnostic test, where influenza sample from the child from Imperial County was tested. By April 21, enhanced surveillance was established to search for additional cases in both California and Texas and the CDC determined that the virus strain was genetically similar to the previously known A(H1N1) swine flu circulating among pigs in the United States since about 1999. It
2907-617: A new count of deaths, including some without laboratory-confirmed swine flu. The Agriculture Department reported on October 16 that three pigs at the Minnesota State Fair, in St. Paul, were tested positive in late August for H1N1 virus, which were the first cases in the country, although infected pigs had been found in eight other countries. There were 103 pigs tested at the Fair, including the three infected, though all appeared healthy. Scientists said
3078-444: A part of a virus that is essential for its invasion). More narrowly, an antibody ( Ab ) can refer to the free (secreted) form of these proteins, as opposed to the membrane-bound form found in a B cell receptor. The term immunoglobulin can then refer to both forms. Since they are, broadly speaking, the same protein, the terms are often treated as synonymous. To allow the immune system to recognize millions of different antigens,
3249-487: A population of human hosts in which zoonosis and reassortment can co-occur. Vaccination of these workers against influenza and surveillance for new influenza strains among this population may therefore be an important public health measure. Transmission of influenza from swine to humans who work with swine was documented in a small surveillance study performed in 2004 at the University of Iowa. This study, among others, forms
3420-428: A second infection causes death, usually pneumonia (of which 48,657 of 55,477 official deaths in 2006 occurred in people aged 65 years and older). The final estimate was of over 12,000 deaths throughout the pandemic (April 2009 – April 2010). The CDC reported that during the outbreak about half of all influenza viruses being detected through laboratory reports were 2009 H1N1 viruses, with the other half being those of
3591-462: A secondary immune response, undergoing class switching, affinity maturation, and differentiating into antibody-secreting cells. Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. herpes zoster ). Durable protection from infections caused by
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#17333735056993762-432: A specific antigen is present in the body and triggers B cell activation. The BCR is composed of surface-bound IgD or IgM antibodies and associated Ig-α and Ig-β heterodimers , which are capable of signal transduction . A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface. Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate
3933-439: A strain of H4N6 crossed the species barrier from birds to pigs, but was contained on a single farm. The H1N1 form of swine flu is one of the descendants of the strain that caused the 1918 flu pandemic . As well as persisting in pigs, the descendants of the 1918 virus have also circulated in humans through the 20th century, contributing to the normal seasonal epidemics of influenza. However, direct transmission from pigs to humans
4104-429: A strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis . Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival allowing the average affinity of antibodies to increase over time. The process of generating antibodies with increased binding affinities
4275-449: A substantial number of cases where the strain could not be subtyped. The proportion of US deaths due to pneumonia and influenza climbed above the epidemic threshold in the 2007–2008 winter flu season but not in the 2008–2009 season. Although the 2009 H1N1 outbreak reached epidemic levels of infection early in 2009, it did not contribute to epidemic levels of pneumonia and influenza related deaths until October 2009. In early October 2009,
4446-478: A sudden fever, cough, or muscle aches, should stay away from work or public transportation and should contact a doctor for advice. Social distancing can be another infection control tactic. Individuals should avoid other people who might be infected or if infected themselves isolate from others for the duration of the infection. During active outbreaks, avoiding large gatherings, increasing physical distance in public places, or if possible remaining at home as much as
4617-496: A widespread distribution. Outbreaks in swine are common and cause significant economic losses in industry, primarily by causing stunting and extended time to market. For example, this disease costs the British meat industry about £65 million every year. The 1918 flu pandemic in humans was associated with H1N1 and influenza appearing in pigs; this may reflect a zoonosis either from swine to humans, or from humans to swine. Although it
4788-503: Is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. H3N2 evolved from H2N2 by antigenic shift . In August 2004, researchers in China found H5N1 in pigs. These H5N1 infections may be common. In a survey of 10 apparently healthy pigs housed near poultry farms in West Java , where avian flu had broken out, five of
4959-459: Is respiratory failure . Other causes of death are pneumonia (leading to sepsis ), high fever (leading to neurological problems), dehydration (from excessive vomiting and diarrhea ), electrolyte imbalance and kidney failure . Fatalities are more likely in young children and the elderly. Influenza is common in pigs. About half of breeding pigs in the USA have been exposed to the virus. Antibodies to
5130-418: Is a major method of limiting swine-to-human transmission. Risk factors that may contribute to the swine-to-human transmission include smoking and, especially, not wearing gloves when working with sick animals, thereby increasing the likelihood of subsequent hand-to-eye, hand-to-nose, or hand-to-mouth transmission. Influenza spreads between humans when infected people cough or sneeze, then other people breathe in
5301-522: Is also partitioned into two antigen-binding fragments (Fab), containing one V L , V H , C L , and C H 1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape. In between them is a hinge region of the heavy chains, whose flexibility allows antibodies to bind to pairs of epitopes at various distances, to form complexes ( dimers , trimers, etc.), and to bind effector molecules more easily. In an electrophoresis test of blood proteins , antibodies mostly migrate to
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5472-490: Is also reduced by disinfecting household surfaces, which can be done effectively with a diluted chlorine bleach solution. Influenza can spread in coughs or sneezes, but an increasing body of evidence shows small droplets containing the virus can linger on tabletops, telephones, and other surfaces and be transferred via the fingers to the eyes, nose, or mouth. Alcohol-based gel or foam hand sanitizers work well to destroy viruses and bacteria. Anyone with flu-like symptoms, such as
5643-429: Is approximately the number that usually dies in an entire flu season. Nineteen of the forty-three were teenagers while sixteen were between ages five to eleven. The rest were under five. It is reported that the severity of the disease was not increasing. About fifteen to twenty percent of the patients hospitalized for the flu were placed in the intensive care unit, a level similar to that for seasonal flu. Projections of
5814-469: Is broken by the activity of a series of enzymes at two selected S-regions. The variable domain exon is rejoined through a process called non-homologous end joining (NHEJ) to the desired constant region (γ, α or ε). This process results in an immunoglobulin gene that encodes an antibody of a different isotype. 2009 swine flu outbreak in the United States The 2009 flu pandemic in
5985-415: Is called affinity maturation . Affinity maturation occurs in mature B cells after V(D)J recombination, and is dependent on help from helper T cells . Isotype or class switching is a biological process occurring after activation of the B cell, which allows the cell to produce different classes of antibody (IgA, IgE, or IgG). The different classes of antibody, and thus effector functions, are defined by
6156-448: Is closer to human IgG2 than human IgG1 in terms of its function. The term humoral immunity is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from cell-mediated immunity , which generally describes the responses of T cells (especially cytotoxic T cells). In general, antibodies are considered part of
6327-544: Is compensated for through memory B cells: novel variants of a microbe that still retain structural features of previously encountered antigens can elicit memory B cell responses that adapt to those changes. It has been suggested that long-lived plasma cells secrete B cell receptors with higher affinity than those on the surfaces of memory B cells, but findings are not entirely consistent on this point. Antibodies are heavy (~150 k Da ) proteins of about 10 nm in size, arranged in three globular regions that roughly form
6498-488: Is estimated that, in the 2009 flu pandemic , 11–21% of the then global population (of about 6.8 billion), equivalent to around 700 million to 1.4 billion people, contracted the illness—more, in absolute terms, than the Spanish flu pandemic . There were 18,449 confirmed fatalities. However, in a 2012 study, the CDC estimated more than 284,000 possible fatalities worldwide, with numbers ranging from 150,000 to 575,000. In August 2010,
6669-422: Is feasible can prevent further spread of disease. Public health and other responsible authorities have action plans which may request or require social distancing actions, depending on the severity of the outbreak. Vaccines are available for different kinds of swine flu. The U.S. Food and Drug Administration (FDA) approved the new swine flu vaccine for use in the United States on September 15, 2009. Studies by
6840-507: Is large and contains several distinct gene loci for each domain of the antibody—the chromosome region containing heavy chain genes ( IGH@ ) is found on chromosome 14 , and the loci containing lambda and kappa light chain genes ( IGL@ and IGK@ ) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences between
7011-405: Is no formal national surveillance system in the United States to determine what viruses are circulating in pigs, an informal surveillance network in the United States is part of a world surveillance network. As swine influenza is rarely fatal to pigs, little treatment beyond rest and supportive care is required. Instead, veterinary efforts are focused on preventing the spread of the virus throughout
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7182-416: Is not certain in which direction the virus was transferred, some evidence suggests that in this case pigs caught the disease from humans. For instance, swine influenza was only noted as a new disease of pigs in 1918 after the first large outbreaks of influenza amongst people. Although a recent phylogenetic analysis of more recent strains of influenza in humans, birds, and other animals including swine suggests
7353-427: Is obviously a cause for concern ... but it is not a cause for alarm." Obama suggested that U.S. schools should consider shutting down, as a future possibility, if their students were to become infected. White House Press Secretary Robert Gibbs said the effort to get a team in place to respond to the health scare had not been hindered by the lack of a secretary of Health and Human Services or appointees in any of
7524-522: Is part of Department of Health and Human Services.) The FDA stated it was also responding to this threat by: On May 6, 2009, the FDA announced that it had approved a new manufacturing facility for seasonal flu vaccine, owned by Sanofi Pasteur, which could also be used for manufacturing a vaccine for the new H1N1 flu strain. The FDA also issued a warning for consumers to be wary of products claiming to cure or prevent swine flu. Secretary Napolitano stated that DHS
7695-458: Is present, ensuring that antibody levels to the antigen in question do not fall to 0, provided the plasma cell stays alive. The rate of antibody secretion, however, can be regulated, for example, by the presence of adjuvant molecules that stimulate the immune response such as TLR ligands. Long-lived plasma cells can live for potentially the entire lifetime of the organism. Classically, the survival niches that house long-lived plasma cells reside in
7866-448: Is rare, with only 12 recorded cases in the U.S. since 2005. Nevertheless, the retention of influenza strains in pigs after these strains have disappeared from the human population might make pigs a reservoir where influenza viruses could persist, later emerging to reinfect humans once human immunity to these strains has waned. Swine flu has been reported numerous times as a zoonosis in humans, usually with limited distribution, rarely with
8037-430: Is required. IgA tetramers and pentamers have also been reported. Antibodies also form complexes by binding to antigen: this is called an antigen-antibody complex or immune complex . Small antigens can cross-link two antibodies, also leading to the formation of antibody dimers, trimers, tetramers, etc. Multivalent antigens (e.g., cells with multiple epitopes) can form larger complexes with antibodies. An extreme example
8208-625: Is reversible, and the antibody's affinity towards an antigen is relative rather than absolute. Relatively weak binding also means it is possible for an antibody to cross-react with different antigens of different relative affinities. The main categories of antibody action include the following: More indirectly, an antibody can signal immune cells to present antibody fragments to T cells , or downregulate other immune cells to avoid autoimmunity . Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in
8379-410: Is the clumping, or agglutination , of red blood cells with antibodies in blood typing to determine blood groups : the large clumps become insoluble, leading to visually apparent precipitation . The membrane-bound form of an antibody may be called a surface immunoglobulin (sIg) or a membrane immunoglobulin (mIg). It is part of the B cell receptor (BCR), which allows a B cell to detect when
8550-513: Is the most frequent. Since 2009 another subtype, pdmH1N1(2009), emerged globally and also in European pig population. The prevalence varies from country to country but all of the subtypes are continuously circulating in swine herds. In the EU region whole-virus vaccines are available which are inactivated and adjuvanted. Vaccination of sows is common practice and reveals also a benefit to young pigs by prolonging
8721-463: Is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking
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#17333735056998892-529: Is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue. Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens. It has been estimated that humans generate about 10 billion different antibodies, each capable of binding
9063-451: Is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment. Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called switch (S) regions , found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand
9234-526: The Centers for Disease Control and Prevention (CDC) activated its Emergency Operations Center and declared a public health emergency. On April 25, the World Health Organization (WHO) declared a public health emergency of international concern. WHO declared H1N1 a pandemic on June 11. By the end of May, the flu had infected people in all 50 states. As of June 16, the total number of confirmed cases
9405-463: The National Institutes of Health show a single dose creates enough antibodies to protect against the virus within about 10 days. In the aftermath of the 2009 pandemic, several studies were conducted to see which population groups were most likely to have received an influenza vaccine. These studies demonstrated that caucasians are much more likely to be vaccinated for seasonal influenza and for
9576-532: The World Health Organization declared a public health emergency, followed concurringly by the Obama administration on April 26. The U.S. Centers for Disease Control and Prevention (CDC) reported that during the outbreak about half of all influenza viruses being reported were 2009 H1N1 viruses, with the other half being those of the regular seasonal influenza. Unique to this particular strain, about 60% of
9747-470: The World Health Organization declared the swine flu pandemic officially over. Subsequent cases of swine flu were reported in India in 2015, with over 31,156 positive test cases and 1,841 deaths . In pigs, a swine influenza infection produces fever , lethargy , discharge from the nose or eyes, sneezing , coughing , difficulty breathing , eye redness or inflammation, and decreased appetite. In some cases,
9918-416: The adaptive immune system , though this classification can become complicated. For example, natural IgM, which are made by B-1 lineage cells that have properties more similar to innate immune cells than adaptive, refers to IgM antibodies made independently of an immune response that demonstrate polyreactivity- they recognize multiple distinct (unrelated) antigens. These can work with the complement system in
10089-461: The antigenic shifts can occur that create new influenza strains. The transmission from swine to humans is believed to occur mainly in swine farms, where farmers are in close contact with live pigs. Although strains of swine influenza are usually not able to infect humans, it may occasionally happen, so farmers and veterinarians are encouraged to use face masks when dealing with infected animals. The use of vaccines on swine to prevent their infection
10260-639: The antiviral adamantanes amantadine and rimantadine . Of the three genera of influenza viruses that cause human flu , two also cause influenza in pigs, with influenza A being common in pigs and influenza C being rare. Influenza B has not been reported in pigs. Within influenza A and influenza C, the strains found in pigs and humans are largely distinct, although because of reassortment there have been transfers of genes among strains crossing swine, avian, and human species boundaries. Influenza viruses infect both humans and pigs, but do not infect birds. Transmission between pigs and humans have occurred in
10431-736: The iota (ι) chain, are found in other vertebrates like sharks ( Chondrichthyes ) and bony fishes ( Teleostei ). In most placental mammals , the structure of antibodies is generally the same. Jawed fish appear to be the most primitive animals that are able to make antibodies similar to those of mammals, although many features of their adaptive immunity appeared somewhat earlier. Cartilaginous fish (such as sharks) produce heavy-chain-only antibodies (i.e., lacking light chains) which moreover feature longer chain pentamers (with five constant units per molecule). Camelids (such as camels, llamas, alpacas) are also notable for producing heavy-chain-only antibodies. The antibody's paratope interacts with
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#173337350569910602-437: The "classical" complement system. This results in the killing of bacteria in two ways. First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization ; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement system components form a membrane attack complex to assist antibodies to kill
10773-562: The 1918 outbreak in humans followed a reassortment event within a mammal, the exact origin of the 1918 strain remains elusive. It is estimated that anywhere from 50 to 100 million people were killed worldwide. The swine flu was initially seen in the US in April 2009, where the strain of the particular virus was a mixture from 3 types of strains. Six of the genes are very similar to the H1N2 influenza virus that
10944-501: The 2009 H1N1 influenza cases were occurring among people between 5 years and 24 years of age, and 40% of the hospitalizations were occurring among children and young adults. About 80% of the deaths were in people younger than 65 years of age. The CDC noted that this differed greatly from typical seasonal influenza epidemics, during which about 70% to 90% of deaths are estimated to occur in people 65 years and older. Antibody studies showed that children had no existing cross-reactive antibody to
11115-502: The 2009 H1N1 influenza virus, while about one-third of adults older than 60 years of age had cross-reactive antibody. By April 21, 2009, CDC had begun working to develop a virus that could be used to make a vaccine to protect against the new virus. Following preparation for distribution beginning in June, the first doses were administered in October 2009. On August 10, 2010, WHO declared an end to
11286-459: The 2009 outbreak, an elevated percentage of patients reporting diarrhea and vomiting . Because these symptoms are not specific to swine flu, a differential diagnosis of probable swine flu requires not only symptoms, but also a high likelihood of swine flu due to the person's recent and past medical history. For example, during the 2009 swine flu outbreak in the United States , the CDC advised physicians to "consider swine influenza infection in
11457-427: The 97 recent H3N2 isolates examined, only 41 isolates had strong serologic cross-reactions with antiserum to three commercial SIV vaccines. Since the protective ability of influenza vaccines depends primarily on the closeness of the match between the vaccine virus and the epidemic virus, the presence of nonreactive H3N2 SIV variants suggests current commercial vaccines might not effectively protect pigs from infection with
11628-610: The BCRs from most other cell signaling receptors. These patches may improve the efficiency of the cellular immune response . In humans, the cell surface is bare around the B cell receptors for several hundred nanometers, which further isolates the BCRs from competing influences. Antibodies can come in different varieties known as isotypes or classes . In humans there are five antibody classes known as IgA, IgD, IgE, IgG, and IgM, which are further subdivided into subclasses such as IgA1, IgA2. The prefix "Ig" stands for immunoglobulin , while
11799-535: The CDC reported 57 million Americans had been sickened, 257,000 had been hospitalized and 11,690 people had died (including 1,180 children) due to flu from April through to mid-January. The Centers for Disease Control and Prevention (CDC) identified the first two A/09(H1N1) swine flu cases in California on April 17, 2009, via the Border Infectious Disease Program, for a San Diego County child, and
11970-528: The CDC reported one death, 286 confirmed cases of H1N1 flu across 36 states, 35 hospitalizations, and expected H1N1 to eventually spread to all states. A large number of cases, according to medics, have happened in the days that preceded the launch of the alert and came out only in these days due to a massive backlog. By May 5, 2009, the number had risen to 403 and a second death was reported in Texas. The CDC and government officials had expressed cautious optimism about
12141-709: The Center for Disease Control and Prevention confirmed 145 human cases (113 in Indiana, 30 in Ohio, one in Hawaii and one in Illinois) of H3N2v since July 2012. The death of a 61-year-old Madison County, Ohio woman is the first in the USA associated with a new swine flu strain. She contracted the illness after having contact with hogs at the Ross County Fair. The CDC recommends real-time PCR as
12312-450: The Centers for Disease Control and Prevention announced that swine flu was widespread across the country. It also said there was significant flu activity in virtually all states, which was considered to be quite unusual for this time of year. There was particular worry about pregnant women. As of late August, 100 had been hospitalized in intensive care units and 28 had died since the beginning of
12483-513: The F V region. It is the subregion of Fab that binds to an antigen. More specifically, each variable domain contains three hypervariable regions – the amino acids seen there vary the most from antibody to antibody. When the protein folds, these regions give rise to three loops of β-strands , localized near one another on the surface of the antibody. These loops are referred to as the complementarity-determining regions (CDRs), since their shape complements that of an antigen. Three CDRs from each of
12654-455: The Fc region and influence interactions with effector molecules. The N-terminus of each chain is situated at the tip. Each immunoglobulin domain has a similar structure, characteristic of all the members of the immunoglobulin superfamily : it is composed of between 7 (for constant domains) and 9 (for variable domains) β-strands , forming two beta sheets in a Greek key motif . The sheets create
12825-486: The Fc region of an antibody, while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway . Another role of the Fc region is to selectively distribute different antibody classes across the body. In particular, the neonatal Fc receptor (FcRn) binds to the Fc region of IgG antibodies to transport it across
12996-768: The H1N1 strain than African Americans. This could be due to several factors. Historically, there has been mistrust of vaccines and of the medical community from African Americans. Many African Americans do not believe vaccines or doctors to be effective. This mistrust stems from the exploitation of the African American communities during studies like the Tuskegee study . Additionally, vaccines are typically administered in clinics, hospitals, or doctor's offices. Many people of lower socioeconomic status are less likely to receive vaccinations because they do not have health insurance. Although there
13167-710: The Incident Commander, to augment the ongoing investigation of human cases of swine influenza A (H1N1). More than 250 CDC professionals worked from the CDC EOC as part of the agency's response. As of May 4, 2009, the CDC reported that it had deployed 25% of the supplies and medicines in the Strategic National Stockpile to the various states. As of April 29, only the CDC could confirm U.S. swine flu cases. Besser stated during an April 30 press briefing that California and New York had diagnostic test kits, and that
13338-603: The Pandemic Alert level to Phase 6, the highest on the WHO scale and congruent with U.S. Federal Government Response Stages 3–6. An official for the White House said on April 24 that "the White House is taking the situation seriously and monitoring for any new developments. The president has been fully briefed." President Barack Obama stated that "We are closely monitoring the emerging cases of swine flu." He also noted, "This
13509-531: The Senate on April 28, 2009, with a vote of 65–31. On October 24, President Obama declared the 2009 H1N1 swine flu a national emergency. The declaration made it easier for U.S. medical facilities to handle a surge in flu patients by allowing the waiver of some requirements of Medicare , Medicaid and other federal health insurance programs as needed. During the week of April 19, 2009, the CDC activated its Emergency Operations Center (EOC), with RADM Stephen Redd as
13680-539: The State Department did recommend US citizens avoid non-essential travel to Mexico. The Department of Agriculture (USDA) reported no swine in the US have been infected so far, but the USDA is monitoring swine across the US for signs of infection. The Department of Commerce sent a letter to Russia and China requesting that those countries lift their ban on American pork products. The Department of Defense (DOD) monitored
13851-438: The U.S. due to normal influenza, which is higher than the 150 total deaths worldwide from the swine flu up to that time. As of May 28, 2010, the official U.S. death toll attributed directly to the novel H1N1 and seasonal influenza was 2,117. This total exceeds the 849 U.S. deaths directly attributed to seasonal influenza in 2006. Many of the other deaths commonly attributed to influenza are caused by complicated influenza, where
14022-474: The United States was caused by a novel strain of the Influenza A/H1N1 virus, commonly referred to as " swine flu ", that was first detected on 15 April 2009. While the 2009 H1N1 virus strain was commonly referred to as "swine flu", there is no evidence that it is endemic to pigs (i.e. actually a swine flu) or of transmission from pigs to people; instead, the virus spreads from person to person. On April 25,
14193-491: The V, D and J gene segments exist, and are tandemly arranged in the genomes of mammals . In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates
14364-595: The WHO's decision to raise its pandemic alert to level 5, saying: I don't agree with (the WHO) because I think it's a panic metre, not a pandemic metre. [...] If that flu-like illness is not deadly, I don't know what the cause for alarm is for people who are not really sickened by this virus. [...] I'm really eager to know how much worse this is than seasonal flu. So far it's looking like it's not that serious. CNN noted on April 28, 2009, that in any individual week between January 1 and April 18, there had been at least 800 deaths in
14535-450: The adaptive immune system is regulated by interactions between idiotypes. The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen. Effector cells (such as macrophages or natural killer cells ) bind via their Fc receptors (FcR) to
14706-495: The aerosols produced by pigs coughing or sneezing are also an important means of infection. The virus usually spreads quickly through a herd, infecting all the pigs within just a few days. Transmission may also occur through wild animals, such as wild boar , which can spread the disease between farms. People who work with poultry and swine, especially those with intense exposures, are at increased risk of zoonotic infection with influenza virus endemic in these animals, and constitute
14877-410: The antibody (also known as effector functions), in addition to some other structural features. Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response. Between species, while classes and subclasses of antibodies may be shared (at least in name), their functions and distribution throughout the body may be different. For example, mouse IgG1
15048-683: The antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination discussed below. Somatic recombination of immunoglobulins, also known as V(D)J recombination , involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments. V, D and J segments are found in Ig heavy chains , but only V and J segments are found in Ig light chains . Multiple copies of
15219-556: The antigen's epitope. An antigen usually contains different epitopes along its surface arranged discontinuously, and dominant epitopes on a given antigen are called determinants. Antibody and antigen interact by spatial complementarity (lock and key). The molecular forces involved in the Fab-epitope interaction are weak and non-specific – for example electrostatic forces , hydrogen bonds , hydrophobic interactions , and van der Waals forces . This means binding between antibody and antigen
15390-421: The antigen-binding sites at both tips of the antibody come in an equally wide variety. The rest of the antibody structure is much less variable; in humans, antibodies occur in five classes , sometimes called isotypes : IgA , IgD , IgE , IgG , and IgM . Human IgG and IgA antibodies are also divided into discrete subclasses (IgG1, IgG2, IgG3, IgG4; IgA1 and IgA2). The class refers to the functions triggered by
15561-401: The bacterium directly (bacteriolysis). To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate . Since an antibody has at least two paratopes, it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against
15732-576: The basis of a recommendation that people whose jobs involve handling poultry and swine be the focus of increased public health surveillance. Other professions at particular risk of infection are veterinarians and meat processing workers, although the risk of infection for both of these groups is lower than that of farm workers. Pigs are unusual because they can be infected with influenza strains that usually infect three different species: pigs, birds, and humans. Within pigs, influenza viruses may exchange genes and produce novel strains. Avian influenza virus H3N2
15903-434: The bloodstream, they are said to be part of the humoral immune system . Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Antibodies contribute to immunity in three ways: They prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating
16074-424: The body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures. At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in
16245-477: The bone marrow, though it cannot be assumed that any given plasma cell in the bone marrow will be long-lived. However, other work indicates that survival niches can readily be established within the mucosal tissues- though the classes of antibodies involved show a different hierarchy from those in the bone marrow. B cells can also differentiate into memory B cells which can persist for decades similarly to long-lived plasma cells. These cells can be rapidly recalled in
16416-430: The cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell . In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane -bound form. Some daughter cells of the activated B cells undergo isotype switching , a mechanism that causes the production of antibodies to change from IgM or IgD to
16587-423: The classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Antibodies are produced exclusively by B cells in response to antigens where initially, antibodies are formed as membrane-bound receptors, but upon activation by antigens and helper T cells, B cells differentiate to produce soluble antibodies. Many natural antibodies are directed against
16758-471: The common cold) accounting for 5.5% of doctors visits, down sharply from 8% in late October, the peak of the second wave. However, taking the vaccine is still urged by the CDC, as a third wave of the disease may sweep across the US, possibly in January/February 2010. As of December 24, the second wave of H1N1 has clearly peaked, with pneumonia and influenza deaths falling below the epidemic threshold for
16929-403: The constant (C) regions of the immunoglobulin heavy chain. Initially, naive B cells express only cell-surface IgM and IgD with identical antigen binding regions. Each isotype is adapted for a distinct function; therefore, after activation, an antibody with an IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from
17100-637: The department's 19 key posts. The president's nominee, Kansas Gov. Kathleen Sebelius , was still awaiting confirmation from the U.S. Senate until passing on April 28. The President had not yet made appointments to either the Commissioner of the Food and Drug Administration , the Surgeon General , or the Director of the Centers for Disease Control and Prevention . The current acting Surgeon General, Steven K. Galson ,
17271-499: The differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the seven days preceding their illness onset." A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab). The most common cause of death
17442-410: The disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut. These antibodies undergo quality checks in the endoplasmic reticulum (ER), which contains proteins that assist in proper folding and assembly. Rejection of xenotransplantated organs
17613-407: The disease. The vaccination program was plagued by delays and public relations problems. On October 1, 1976, immunizations began, and three senior citizens died soon after receiving their injections. This resulted in a media outcry that linked these deaths to the immunizations, despite the lack of any proof the vaccine was the cause. According to science writer Patrick Di Justo, however, by the time
17784-414: The diversity of the antibody pool and impacts the antibody's antigen-binding affinity . Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a stronger interaction (high affinity). B cells that express high affinity antibodies on their surface will receive
17955-583: The earliest phases of an immune response to help facilitate clearance of the offending antigen and delivery of the resulting immune complexes to the lymph nodes or spleen for initiation of an immune response. Hence in this capacity, the function of antibodies is more akin to that of innate immunity than adaptive. Nonetheless, in general antibodies are regarded as part of the adaptive immune system because they demonstrate exceptional specificity (with some exception), are produced through genetic rearrangements (rather than being encoded directly in germline ), and are
18126-602: The early phases of the immune response (classically described as arising extrafollicularly rather than from the germinal center ) which have the potential to differentiate further into plasma cells. The literature is sloppy at times and often describes plasmablasts as just short-lived plasma cells- formally this is incorrect. Plasma cells, in contrast, do not divide (they are terminally differentiated ), and rely on survival niches comprising specific cell types and cytokines to persist. Plasma cells will secrete huge quantities of antibody regardless of whether or not their cognate antigen
18297-569: The eight viral gene segments in the 2009 flu outbreak. Antibody An antibody ( Ab ) or immunoglobulin ( Ig ) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses , including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens . Antigen literally means "antibody generator", as it
18468-472: The evolution of strains that can be passed on to other mammals, such as humans. Direct transmission of a swine flu virus from pigs to humans is possible ( zoonotic swine flu). Fifty cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia , one had Hodgkin's lymphoma , and two were known to be previously healthy. No medical history
18639-461: The farm or to other farms. Vaccination and animal management techniques are most important in these efforts. Antibiotics are also used to treat the disease, which, although they have no effect against the influenza virus, do help prevent bacterial pneumonia and other secondary infections in influenza-weakened herds. In Europe the avian-like H1N1 and the human-like H3N2 and H1N2 are the most common influenza subtypes in swine, of which avian-like H1N1
18810-644: The first time in 11 weeks, and the proportion of doctors visits due to influenza-like illness falling to baseline (2.3%), down from 5.5% 1 month before, on November 20. However, it was reported that influenza activity was beginning to increase in West Virginia, with 5.2% of patients treated by West Virginia health care providers having influenza-like illness, a major increase from 2% of patients treated by West Virginia health care providers having influenza-like illness in November. On August 10, 2010, WHO declared an end to
18981-432: The flu using mechanisms already in place for its Vaccines for Children (VFC) program. On October 24, and the CDC said more than 1,000 had died from the flu. President Obama declared a national emergency. On December 10, 2009, the CDC reported an estimated 50 million Americans or 1 in 6 had been infected and 10,000 had died. On December 23, 2009, the CDC reported a reduction of the disease by 59% percent. On February 12,
19152-606: The flu death toll in Mexico could be lower than first thought. Gerald Evans, head of the Association of Medical Microbiology and Infectious Disease Canada and a member of a federal pandemic-planning committee, said on April 29: There was a lot of speculation and what seemed to be evidence there were dozens and dozens of deaths. Careful analysis showed these people likely died of something else, and not influenza. That's really good news, and that would fit with what we've seen outside of Mexico. Another Canadian expert, Neil Rau, criticized
19323-612: The following 60 years, swine influenza strains were almost exclusively H1N1. Then, between 1997 and 2002, new strains of three different subtypes and five different genotypes emerged as causes of influenza among pigs in North America. In 1997–1998, H3N2 strains emerged. These strains, which include genes derived by reassortment from human, swine and avian viruses, have become a major cause of swine influenza in North America. Reassortment between H1N1 and H3N2 produced H1N2 . In 1999 in Canada,
19494-414: The genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation , by a process called somatic hypermutation (SHM). SHM results in approximately one nucleotide change per variable gene, per cell division. As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains. This serves to increase
19665-460: The global 2009 H1N1 influenza pandemic. However, the virus continues to circulate as a seasonal flu virus, and cause illness, hospitalization, and deaths worldwide every year. The new strain was identified as a combination of several different strains of Influenzavirus A , subtype H1N1 , including separate strains of this subtype circulating in humans (see human influenza ) and in pigs (see swine influenza ). The strain transmits between humans and
19836-417: The global 2009 H1N1 influenza pandemic. However, the virus continues to circulate as a seasonal flu virus, and cause illness, hospitalization, and deaths worldwide every year. From April 12, 2009, to April 10, 2010, the CDC estimates there were 60.8 million cases (range: 43.3 - 89.3 million), 274,304 hospitalizations (range: 195,086 - 402,719), and 12,469 deaths (range: 8868 - 18,306) in the United States due to
20007-846: The heavy and light chains together form an antibody-binding site whose shape can be anything from a pocket to which a smaller antigen binds, to a larger surface, to a protrusion that sticks out into a groove in an antigen. Typically though, only a few residues contribute to most of the binding energy. The existence of two identical antibody-binding sites allows antibody molecules to bind strongly to multivalent antigen (repeating sites such as polysaccharides in bacterial cell walls , or other sites at some distance apart), as well as to form antibody complexes and larger antigen-antibody complexes . The structures of CDRs have been clustered and classified by Chothia et al. and more recently by North et al. and Nikoloudis et al. However, describing an antibody's binding site using only one single static structure limits
20178-416: The illness and death associated with swine flu involves secondary infection by other pathogens, control strategies that rely on vaccination may be insufficient. Control of swine influenza by vaccination has become more difficult in recent decades, as the evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling
20349-470: The illness, although some people, most commonly children, can remain contagious for up to ten days. Diagnosis can be made by sending a specimen, collected during the first five days, for analysis. Recommendations to prevent the spread of the virus among humans include using standard infection control , which includes frequent washing of hands with soap and water or with alcohol-based hand sanitizers , especially after being out in public. Chance of transmission
20520-547: The infection can cause miscarriage . However, infected pigs may not exhibit any symptoms. Although mortality is usually low (around 1–4%), the virus can cause weight loss and poor growth , in turn causing economic loss to farmers. Infected pigs can lose up to 12 pounds of body weight over a three- to four-week period. Influenza A is responsible for infecting swine and was first identified in 1918. Because both avian and mammalian influenza viruses can bind to receptors in pigs, pigs have often been seen as "mixing vessels", facilitating
20691-403: The infection when the virus strains match enough to have significant cross-protection, and custom (autogenous) vaccines made from the specific viruses isolated are created and used in the more difficult cases. Present vaccination strategies for SIV control and prevention in swine farms typically include the use of one of several bivalent SIV vaccines commercially available in the United States. Of
20862-487: The influenza A subtype. However, in 2007, human infection with a novel influenzavirus A became a nationally notifiable condition. Novel influenza A virus infections include all human infections with influenza A viruses that are different from currently circulating human influenza H1 and H3 viruses. These viruses include those that are subtyped as nonhuman in origin and those that are unsubtypable with standard methods and reagents. The new strain responsible for this outbreak
21033-769: The invading microbe. The activation of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity (ADCC) – this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer . The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens. Humans and higher primates also produce "natural antibodies" that are present in serum before viral infection. Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination , other foreign antigen exposure or passive immunization . These antibodies can activate
21204-414: The kits would be sent to all states starting the following day. On May 6, the CDC announced that testing kits were now available for all states. It was expected this would generate an increase in the number of confirmed cases as more states began doing their own tests. In the United States, the majority of the 70 National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories do not report
21375-459: The last, gamma globulin fraction. Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ . This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ (gamma) heavy chains which characterize the IgG class of antibodies. The variable domains can also be referred to as
21546-410: The limiting effectiveness of school closure as a control measure. The new advice given stated, "Decisions about school closure should be at the discretion of local authorities based on local considerations, including public concern and the impact of school absenteeism and staffing shortages." The Food and Drug Administration (FDA) authorized emergency use of medicines and diagnostic tests for flu. (FDA
21717-593: The maternally level of antibodies. Several commercial vaccines are available including a trivalent one being used in sow vaccination and a vaccine against pdmH1N1(2009). In vaccinated sows multiplication of viruses and virus shedding are significantly reduced. If a human becomes sick with swine flu, antiviral drugs can make the illness milder and make the patient feel better faster. They may also prevent serious flu complications. For treatment, antiviral drugs work best if started soon after getting sick (within two days of symptoms). Beside antivirals, supportive care at home or in
21888-500: The method of choice for diagnosing H1N1. The oral or nasal fluid collection and RNA virus-preserving filter-paper card is commercially available. This method allows a specific diagnosis of novel influenza (H1N1) as opposed to seasonal influenza . Near-patient point-of-care tests are in development. Prevention of swine influenza has three components: prevention in pigs, prevention of transmission to humans, and prevention of its spread among humans. Proper handwashing techniques can prevent
22059-520: The mid-20th century, the identification of influenza subtypes was made possible, allowing accurate diagnosis of transmission to humans. Since then, only 50 such transmissions have been confirmed. These strains of swine flu rarely pass from human to human. Symptoms of zoonotic swine flu in humans are similar to those of influenza and influenza-like illness and include chills , fever , sore throat , muscle pains , severe headache , coughing , weakness , shortness of breath, and general discomfort . It
22230-474: The most common strains worldwide. In the United States , the H1N1 subtype was exclusively prevalent among swine populations before 1998. Since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants , containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages. In August 2012,
22401-557: The other antibody isotypes, IgE, IgA, or IgG, that have defined roles in the immune system. In mammals there are two types of immunoglobulin light chain , which are called lambda (λ) and kappa (κ). However, there is no known functional difference between them, and both can occur with any of the five major types of heavy chains. Each antibody contains two identical light chains: both κ or both λ. Proportions of κ and λ types vary by species and can be used to detect abnormal proliferation of B cell clones. Other types of light chains, such as
22572-557: The outbreak in April. On October 1, it was acknowledged that a recruit in basic training in Fort Jackson, South Carolina, was the Army's first swine flu death. The recruit fell ill on September 1 and died of pneumonia on September 10. Dell Children's Medical Center in Austin, Texas, erected two tents in its parking lot to handle emergency room visits, and hospitals around Colorado Springs recorded
22743-487: The past. For example, influenza C caused small outbreaks of a mild form of influenza amongst children in Japan and California. As a result of the limited host range and lack of genetic diversity in influenza C, this form of influenza does not cause pandemics in humans. Swine influenza is caused by influenza A subtypes H1N1 , H1N2 , H2N3 , H3N1 , and H3N2 . In pigs, four influenza A virus subtypes (H1N1, H1N2, H3N2 and H7N9) are
22914-584: The pathogen in cells that recognize their Fc region. Those cells that recognize coated pathogens have Fc receptors, which, as the name suggests, interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose , mast cells and neutrophils will degranulate , natural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of
23085-455: The pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway . Antibodies will also trigger vasoactive amine degranulation to contribute to immunity against certain types of antigens (helminths, allergens). Antibodies that bind to surface antigens (for example, on bacteria) will attract the first component of the complement cascade with their Fc region and initiate activation of
23256-557: The pig samples contained the H5N1 virus. The Indonesian government found similar results in the same region, though additional tests of 150 pigs outside the area were negative. The influenza virion is roughly spherical. It is an enveloped virus; the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. Inserted into the lipid membrane are glycoprotein "spikes" of hemagglutinin (HA) and neuraminidase (NA). The combination of HA and NA proteins determine
23427-599: The placenta, from the mother to the fetus. In addition to this, binding to FcRn endows IgG with an exceptionally long half-life relative to other plasma proteins of 3-4 weeks. IgG3 in most cases (depending on allotype) has mutations at the FcRn binding site which lower affinity for FcRn, which are thought to have evolved to limit the highly inflammatory effects of this subclass. Antibodies are glycoproteins , that is, they have carbohydrates (glycans) added to conserved amino acid residues. These conserved glycosylation sites occur in
23598-437: The presence of these proteins, V(D)J recombination would not occur. After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as allelic exclusion ) thus each B cell can produce antibodies containing only one kind of variable chain. Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells,
23769-416: The regular seasonal influenza viruses. Surveillance reports indicated that about 57% of the 2009 H1N1 influenza confirmed and probable cases were occurring among people between 5 years and 24 years of age, and 41% of the hospitalizations were occurring among older children and young adults. The highest rates of hospitalization were among children younger than 5 years of age; the next highest hospitalization rate
23940-437: The same activated B cell to produce antibodies of different isotypes. Only the constant region of the antibody heavy chain changes during class switching; the variable regions, and therefore antigen specificity, remain unchanged. Thus the progeny of a single B cell can produce antibodies, all specific for the same antigen, but with the ability to produce the effector function appropriate for each antigenic challenge. Class switching
24111-399: The severity and spread of H1N1. Changes in surveillance of cases of influenza-like illness , including new guidelines for identifying cases to test, increased laboratory testing, and new test kits able to distinguish this novel strain, resulted in a spike in the percent of cases tested positive for influenza. Of the positive cases, about a third were due to the novel strain. Also found were
24282-423: The strain involved in the 1918 flu pandemic. Moreover, the ensuing increased surveillance uncovered another strain in circulation in the U.S.: A/Victoria/75 (H3N2) , which spread simultaneously, also caused illness, and persisted until March. Alarmed public health officials decided action must be taken to head off another major pandemic, and urged President Gerald Ford that every person in the U.S. be vaccinated for
24453-451: The subtype of influenza virus (A/H1N1, for example). HA and NA are important in the immune response against the virus, and antibodies against these spikes may protect against infection. The antiviral drugs Relenza and Tamiflu target NA by inhibiting neuraminidase and preventing the release of viruses from host cells. Also embedded in the lipid membrane is the M2 protein , which is the target of
24624-444: The suffix denotes the type of heavy chain the antibody contains: the heavy chain types α (alpha), γ (gamma), δ (delta), ε (epsilon), μ (mu) give rise to IgA, IgG, IgD, IgE, IgM, respectively. The distinctive features of each class are determined by the part of the heavy chain within the hinge and Fc region. The classes differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in
24795-501: The supply of H1N1 vaccine had decreased significantly from a level of 120 million doses ready in October, estimated during the summer, to an estimate of 28 to 30 million doses by the end of the month. On October 14, 11.4 million doses of the H1N1 vaccine were said to be available. As of November 20, 2009, the CDC reported sharp declines in H1N1 activity throughout the United States, with influenza-like illness (which may also include meningitis, pneumonia, strep pharyngitis, gastroenteritis, and
24966-440: The table. For example, IgE antibodies are responsible for an allergic response consisting of histamine release from mast cells , often a sole contributor to asthma (though other pathways exist as do exist symptoms very similar to yet not technically asthma). The antibody's variable region binds to allergic antigen, for example house dust mite particles, while its Fc region (in the ε heavy chains) binds to Fc receptor ε on
25137-440: The truth was known—that the deaths were not proven to be related to the vaccine—it was too late. "The government had long feared mass panic about swine flu—now they feared mass panic about the swine flu vaccinations." This became a strong setback to the program. There were reports of Guillain–Barré syndrome (GBS), a paralyzing neuromuscular disorder, affecting some people who had received swine flu immunizations. Although whether
25308-430: The understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities. In the framework of the immune network theory , CDRs are also called idiotypes. According to immune network theory,
25479-412: The variable domains are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity-determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of
25650-475: The virus are also common in pigs in other countries. The main route of transmission is through direct contact between infected and uninfected animals. These close contacts are particularly common during animal transport. Intensive farming may also increase the risk of transmission, as the pigs are raised in very close proximity to each other. Direct transfer of the virus probably occurs though pigs touching noses or through dried mucus. Airborne transmission through
25821-406: The virus from spreading. Individuals can prevent infection by not touching the eyes, nose, or mouth, distancing from others who display symptoms of the cold or flu, and avoiding contact with others when displaying symptoms. Methods of preventing the spread of influenza among swine include facility management, herd management, and vaccination ( ATCvet code: QI09AA03 ( WHO )). Because much of
25992-464: The virus make a full recovery without requiring medical attention or antiviral drugs. The virus isolated in the 2009 outbreak have been found resistant to amantadine and rimantadine . Swine influenza was first proposed to be a disease related to human flu during the 1918 flu pandemic , when pigs became ill at the same time as humans. The first identification of an influenza virus as a cause of disease in pigs occurred about ten years later, in 1930. For
26163-413: The virus or touch something with the virus on it and then touch their own face. The CDC warned against touching mucosal membranes such as the eyes, nose, or mouth during the 2009 H1N1 pandemic, as these are common entry points for flu viruses. Swine flu cannot be spread by pork products, since the virus is not transmitted through food. The swine flu in humans is most contagious during the first five days of
26334-459: The virus was already spreading widely among people, and, in fact, was more common in humans than in pigs, so humans were more likely to catch it from others than from pigs. In mid-October, it was reported that flu caused by the H1N1 virus was widespread in 41 states, and flu-like illnesses accounted for 6.1 percent of all doctor visits, which was considered high , particularly for October. Forty-three children had died from H1N1 since August 30, which
26505-499: The virus. A follow-up study done in September 2010 showed that the risk of serious illness resulting from the 2009 H1N1 flu was no higher than that of the yearly seasonal flu . For comparison, the CDC estimates the global H1N1 death toll at 284,000 and the WHO estimates that 250,000 to 500,000 people die of seasonal flu annually. The earliest reported cases in the US began appearing in early April 2009, in California. In late April,
26676-565: The virus. On April 28, 2009, the director of the Centers for Disease Control and Prevention confirmed the first official US death of swine flu. Tests confirmed that a 23-month-old toddler from Mexico, who was probably infected there, died on April 27 from the flu while visiting Texas. Cases of H1N1 spread rapidly across the United States, with particularly severe outbreaks in Texas, New York, Utah, and California. Early cases were associated with recent travel to Mexico; many were students who had traveled to Mexico for spring break. On May 4, 2009,
26847-482: The virus. The virus survives in healthy carrier pigs for up to three months and can be recovered from them between outbreaks. Carrier pigs are usually responsible for the introduction of SIV into previously uninfected herds and countries, so new animals should be quarantined . After an outbreak, as immunity in exposed pigs wanes, new outbreaks of the same strain can occur. Swine can be infected by both avian and human flu strains of influenza, and therefore are hosts where
27018-420: Was 27,717 and on June 25, the CDC said there were over one million (1,000,000) cases, most of which had not been reported or diagnosed. Deaths relating to influenza began appearing in the US in late April, and by early June, 15 states had reported fatalities related to or directly occurring from the virus. By October 5, the first doses of an H1N1 vaccine were given in the U.S. The CDC distributed vaccines for
27189-656: Was also currently serving as the Acting Assistant Secretary for Health. On April 30, it was reported that an aide to Steven Chu , the US Energy Secretary, had fallen ill from the virus after helping arrange President Obama's trip to Mexico. However, the White House stated that the President was not at risk of contracting the flu. Kathleen Sebelius was confirmed as the Secretary of Health and Human Services by
27360-490: Was eight months pregnant when she and her husband, Ed, became ill after visiting the hog barn at a county fair in Walworth County, Wisconsin . Barbara died eight days later, after developing pneumonia. The only pathogen identified was an H1N1 strain of swine influenza virus. Doctors were able to induce labor and deliver a healthy daughter before she died. Her husband recovered from his symptoms. Influenza-like illness (ILI)
27531-416: Was established that the virus was a combination of human, North American swine, and Eurasian swine influenza viruses; the viruses from the initial two Californian cases were also noted to be resistant to amantadine and rimantadine , two common influenza antiviral drugs. No contact with pigs was found for any of the seven Californian nor either of the two Texas cases, suggesting human-to-human transmission of
27702-516: Was found in pigs around 2000. On February 5, 1976, a United States army recruit at Fort Dix said he felt tired and weak. He died the next day, and four of his fellow soldiers were later hospitalized. Two weeks after his death, health officials announced the cause of death was a new strain of swine flu. The strain, a variant of H1N1, is known as A/New Jersey/1976 (H1N1). It was detected only from January 19 to February 9 and did not spread beyond Fort Dix. This new strain appeared to be closely related to
27873-434: Was in people 5 years to 24 years of age. Antibody studies showed that children had no existing cross-reactive antibody to the 2009 H1N1 influenza virus, while about one-third of adults older than 60 years of age had cross-reactive antibody. One possible explanation for this pre-existing antibody in older adults was that they may have had previous exposure, either through infection or vaccination, to an influenza A H1N1 virus that
28044-465: Was initially reported to have a relatively high mortality rate in Mexico. In April 2009 the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) expressed serious concerns that the new strain had the potential to become an influenza pandemic . On April 25 it was reported that, because the virus was already widespread, containment would be "nearly impossible." By this time, there had also been speculation that
28215-786: Was more closely related to the 2009 H1N1 flu virus. Based on data from previous influenza pandemics and seasonal influenza, pregnant women had been recognized as a high-risk group early in the outbreak. People with other previously recognized medical conditions that placed them at high risk of complications from seasonal influenza also appeared to be at increased risk of complications from 2009 H1N1 influenza. One report found that seventy-one percent of hospitalized patients had one or more underlying chronic medical conditions and reported deaths had occurred in people ranging in age from 22 months old to 57 years old. Also, only 13% of hospitalizations had occurred in people 50 years and older, and there were few cases and no deaths in people older than 65 years, which
28386-519: Was no community outbreak. In 1998, swine flu was found in pigs in four U.S. states. Within a year, it had spread through pig populations across the United States. Scientists found this virus had originated in pigs as a recombinant form of flu strains from birds and humans. This outbreak confirmed that pigs can serve as a crucible where novel influenza viruses emerge as a result of the reassortment of genes from different strains. Genetic components of these 1998 triple-hybrid strains would later form six out of
28557-579: Was one such virus. Initially the CDC had issued a recommendation that schools close for as long as two weeks if a student catches swine flu. Some school districts closed all schools if a single child was classified as probable. On May 5 the CDC retracted its advice stating that schools that were closed based on previous CDC guidance related to this outbreak may reopen. By that time at least 726 schools nationwide serving more than 480,000 students had closed for at least some period of time. The CDC amended its advice, citing new information on disease severity and
28728-656: Was reported for the remaining case The true rate of infection may be higher, as most cases only cause a very mild disease and may never be reported or diagnosed. According to the United States Centers for Disease Control and Prevention (CDC), in humans the symptoms of the 2009 "swine flu" H1N1 virus are similar to influenza and influenza-like illness . Symptoms include fever , cough , sore throat , watery eyes, body aches, shortness of breath, headache , weight loss, chills , sneezing, runny nose, coughing, dizziness, abdominal pain, lack of appetite, and fatigue . During
28899-437: Was reportedly widespread among the pigs exhibited at the fair. Of the 25 swine exhibitors aged 9 to 19 at the fair, 19 tested positive for antibodies to SIV, but no serious illnesses were seen. The virus was able to spread between people, since one to three health care personnel who had cared for the pregnant woman developed mild, influenza-like illnesses, and antibody tests suggested they had been infected with swine flu, but there
29070-641: Was the principal federal office for incidents such as the H1N1 flu outbreak, and "Under that role, we have been leading a true collaborative effort." The Department of Homeland Security issued a document, dated November 1, 2005, entitled "National Strategy for Pandemic Influenza", detailing planning for potential pandemics. https://web.archive.org/web/20090507013213/http://www.pandemicflu.gov/plan/federal/pandemic-influenza.pdf The State Department suggested travelers to Mexico stay alert and comply with guidance from Mexican public health officials, but did not impose any travel restrictions on US citizens to Mexico. However,
29241-408: Was unusual when compared with seasonal flu. The Federal response remained at US Pandemic Stage 0, congruent with the World Health Organization (WHO) Pandemic Phases 1, 2 and 3; however, the WHO's Pandemic Phase was raised to 4 on April 27, which is congruent with US Pandemic Stage 2. On April 29, the WHO raised the pandemic alert level to phase 5. The United States federal government declared
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