document_title: Phagocyte

question_text: is the process by which phagocytic cells enter the tissues from capillaries

text: Phagocyte

text: History[edit]

text: The Russian zoologist Ilya Ilyich Mechnikov (1845–1916) first recognized that specialized cells were involved in defense against microbial infections. In 1882, he studied motile (freely moving) cells in the larvae of starfishes, believing they were important to the animals' immune defenses. To test his idea, he inserted small thorns from a tangerine tree into the larvae.  After a few hours he noticed that the motile cells had surrounded the thorns.[16] Mechnikov traveled to Vienna and shared his ideas with Carl Friedrich Claus who suggested the name ‘‘phagocyte’’ (from the Greek words phagein, meaning "to eat or devour", and kutos, meaning "hollow vessel"[1]) for the cells that Mechnikov had observed.[17]

text: A year later, Mechnikov studied a fresh water crustacean called Daphnia, a tiny transparent animal that can be examined directly under a microscope. He discovered that fungal spores that attacked the animal were destroyed by phagocytes. He went on to extend his observations to the white blood cells of mammals and discovered that the bacterium Bacillus anthracis could be engulfed and killed by phagocytes, a process that he called phagocytosis.[18] Mechnikov proposed that phagocytes were a primary defense against invading organisms.

text: In 1903, Almroth Wright discovered that phagocytosis was reinforced by specific antibodies that he called opsonins, from the Greek opson, "a dressing or relish".[19] Mechnikov  was awarded (jointly with Paul Ehrlich) the 1908 Nobel Prize in Physiology or Medicine for his work on phagocytes and phagocytosis.[7]

text: Although the importance of these discoveries slowly gained acceptance during the early twentieth century, the intricate relationships between phagocytes and all the other components of the immune system were not known until the 1980s.[20]

text: Phagocytosis[edit]

text: Phagocytosis is the process of taking in particles such as bacteria, parasites, dead host cells, and cellular and foreign debris by a cell.[21] It involves a chain of molecular processes.[22] Phagocytosis occurs after the foreign body, a bacterial cell, for example, has bound to molecules called "receptors" that are on the surface of the phagocyte. The phagocyte then stretches itself around the bacterium and engulfs it. Phagocytosis of bacteria by human neutrophils takes on average nine minutes.[23] Once inside this phagocyte, the bacterium is trapped in a compartment called a phagosome. Within one minute the phagosome merges with either a lysosome or a granule to form a phagolysosome. The bacterium is then subjected to an overwhelming array of killing mechanisms[24] and is dead a few minutes later.[23] Dendritic cells and macrophages are not so fast, and phagocytosis can take many hours in these cells. Macrophages are slow and untidy eaters; they engulf huge quantities of material and frequently release some undigested back into the tissues. This debris serves as a signal to recruit more phagocytes from the blood.[25] Phagocytes have voracious appetites; scientists have even fed macrophages with iron filings and then used a small magnet to separate them from other cells.[26]

text: A phagocyte has many types of receptors on its surface that are used to bind material.[2] They include  opsonin receptors, scavenger receptors, and Toll-like receptors. Opsonin receptors increase the phagocytosis of bacteria that have been coated with immunoglobulin G (IgG) antibodies or with complement. "Complement" is the name given to a complex series of protein molecules found in the blood that destroy cells or mark them for destruction.[27] Scavenger receptors bind to a large range of molecules on the surface of bacterial cells, and Toll-like receptors—so called because of their similarity to well-studied receptors in fruit flies that are encoded by the Toll gene—bind to more specific molecules. Binding to Toll-like receptors increases phagocytosis and causes the phagocyte to release a group of hormones that cause inflammation.[2]

text: Methods of killing[edit]

text: The killing of microbes is a critical function of phagocytes[28] that is performed either within the phagocyte (intracellular killing) or outside of the phagocyte (extracellular killing).

text: Oxygen-dependent intracellular[edit]

text: When a phagocyte ingests bacteria (or any material), its oxygen consumption increases. The increase in oxygen consumption, called a respiratory burst, produces reactive oxygen-containing molecules that are anti-microbial.[29]  The oxygen compounds are toxic to both the invader and the cell itself, so they are kept in compartments inside the cell. This method of killing invading microbes by using the reactive oxygen-containing molecules is referred to as oxygen-dependent intracellular killing, of which there are two types.[14]

text: The first type is the oxygen-dependent production of a superoxide,[2]  which is an oxygen-rich bacteria-killing substance.[30] The superoxide  is converted to hydrogen peroxide and singlet oxygen by an enzyme called superoxide dismutase. Superoxides also react with the hydrogen peroxide to produce hydroxyl radicals, which assist in killing the invading microbe.[2]

text: The second type involves the use of the enzyme myeloperoxidase  from neutrophil granules.[31] When granules fuse with a phagosome, myeloperoxidase is released into the phagolysosome, and this enzyme uses hydrogen peroxide and chlorine to create hypochlorite, a substance used in domestic bleach. Hypochlorite is extremely toxic to bacteria.[2] Myeloperoxidase contains a heme pigment, which accounts for the green color of secretions rich in neutrophils, such as pus and infected sputum.[32]

text: Oxygen-independent intracellular[edit]

text: Phagocytes can also kill microbes by oxygen-independent methods, but these are not as effective as the oxygen-dependent ones. There are four main types. The first uses electrically charged proteins that damage the bacterium's membrane. The second type uses lysozymes; these enzymes break down the bacterial cell wall. The third type uses lactoferrins, which are present in neutrophil granules and remove essential iron from bacteria.[33] The fourth type uses proteases and hydrolytic enzymes; these enzymes are used to digest the proteins of destroyed bacteria.[34]

text: Extracellular[edit]

text: Interferon-gamma—which was once called macrophage activating factor—stimulates macrophages to produce nitric oxide. The source of interferon-gamma can be CD4+ T cells, CD8+ T cells, natural killer cells, B cells, natural killer T cells, monocytes, macrophages, or dendritic cells.[35] Nitric oxide is then released from the macrophage and, because of its toxicity, kills  microbes near the macrophage.[2] Activated macrophages produce and secrete tumor necrosis factor. This cytokine—a class of signaling molecule[36]—kills cancer cells and cells infected by viruses, and helps to activate the other cells of the immune system.[37]

text: In some diseases, e.g., the rare chronic granulomatous disease, the efficiency of phagocytes is impaired, and recurrent bacterial infections are a problem.[38] In this disease there is an abnormality affecting different elements of oxygen-dependent killing.  Other rare congenital abnormalities, such as Chédiak–Higashi syndrome,  are also associated with defective killing of ingested microbes.[39]

text: Viruses[edit]

text: Viruses can reproduce only inside cells, and they gain entry by using many of the receptors involved in immunity. Once inside the cell, viruses use the cell's biological machinery to their own advantage, forcing the cell to make hundreds of identical copies of themselves. Although phagocytes and other components of the innate immune system can, to a limited extent, control viruses, once a virus is inside a cell the adaptive immune responses, particularly the lymphocytes, are more important for defense.[40]  At the sites of viral infections, lymphocytes often vastly outnumber all the other cells of the immune system; this is common in viral meningitis.[41] Virus-infected cells that have been killed by lymphocytes are cleared from the body by phagocytes.[42]

text: Role in apoptosis[edit]

text: In an animal, cells are constantly dying. A balance between cell division and cell death keeps the number of cells relatively constant in adults.[12] There are two different ways a cell can die: by necrosis or by apoptosis. In contrast to necrosis, which often results from disease or trauma, apoptosis—or programmed cell death—is a normal healthy function of cells. The body has to rid itself of millions of dead or dying cells every day, and phagocytes play a crucial role in this process.[43]

text: Dying cells that undergo the final stages of apoptosis[44] display  molecules, such as phosphatidylserine, on their cell surface to attract phagocytes.[45] Phosphatidylserine is normally found on the cytosolic surface of the plasma membrane, but is redistributed during apoptosis to the extracellular surface by a hypothetical protein known as scramblase.[46] These molecules mark the cell for phagocytosis by cells that possess the appropriate receptors, such as macrophages.[47] The removal of dying cells by phagocytes occurs in an orderly manner without eliciting an inflammatory response and is an important function of phagocytes.[48]

text: Interactions with other cells[edit]

text: Phagocytes are usually not bound to any particular organ but move through the body interacting with the other phagocytic and non-phagocytic cells of the immune system. They can communicate with other cells by producing chemicals called cytokines, which recruit other phagocytes to the site of infections or stimulate dormant lymphocytes.[49]  Phagocytes form part of the innate immune system, which animals, including humans, are born with. Innate immunity is very effective but non-specific in that it does not discriminate between different sorts of invaders. On the other hand, the adaptive immune system of jawed vertebrates—the basis of acquired immunity—is highly specialized and can protect against almost any type of invader.[50] The adaptive immune system is not dependent on phagocytes but lymphocytes, which produce protective proteins called antibodies, which tag invaders for destruction and prevent viruses from infecting cells.[51] Phagocytes, in particular dendritic cells and macrophages, stimulate lymphocytes to produce antibodies by an important process called antigen presentation.[52]

text: Antigen presentation[edit]

text: Antigen presentation is a process in which some phagocytes move parts of engulfed materials back to the surface of their cells and "present" them to other cells of the immune system.[53] There are two "professional" antigen-presenting cells: macrophages and dendritic cells.[54] After  engulfment, foreign proteins (the antigens) are broken down into peptides inside dendritic cells and macrophages. These peptides are then bound to the cell's major histocompatibility complex (MHC) glycoproteins, which carry the peptides back to the phagocyte's surface where they can be "presented" to lymphocytes.[15] Mature macrophages do not travel far from the site of infection, but dendritic cells can reach the body's lymph nodes, where there are millions of lymphocytes.[55] This enhances immunity because the lymphocytes respond to the antigens presented by the dendritic cells just as they would at the site of the original infection.[56] But dendritic cells can also destroy or pacify lymphocytes if they recognize components of the host body; this is necessary to prevent autoimmune reactions. This process is called tolerance.[57]

text: Immunological tolerance[edit]

text:
Dendritic cells also promote immunological tolerance,[58] which stops the body from attacking itself. The first type of tolerance is central tolerance, that occurs in the thymus. T cells that bind (via their T cell receptor) to self antigen (presented by dendritic cells on MHC molecules) too strongly are induced to die. The second type of immunological tolerance is peripheral tolerance.
Some self reactive T cells escape the thymus for a number of reasons, mainly due to the lack of expression of some self antigens in the thymus. Another type of T cell T regulatory cells can down regulate self reactive T cells in the periphery.[59] When immunological tolerance fails, autoimmune diseases can follow.[60]

text: Professional phagocytes[edit]

text: Phagocytes of humans and other jawed vertebrates are divided into "professional" and "non-professional" groups based on the efficiency with which they participate in phagocytosis.[9] The  professional phagocytes are the monocytes, macrophages, neutrophils, tissue  dendritic cells and mast cells.[10] One litre of human blood contains about six billion phagocytes.[5]

text: Activation[edit]

text: All phagocytes, and especially macrophages, exist in degrees of readiness.  Macrophages are usually relatively dormant in the tissues and proliferate slowly. In this semi-resting state,  they clear  away dead host cells and other non-infectious debris and rarely take part in antigen presentation.  But, during an infection, they receive chemical signals—usually interferon gamma—which increases their production of MHC II molecules and which prepares them for presenting antigens.  In this state, macrophages are good antigen presenters and  killers.  However, if they receive a signal directly from an invader, they become "hyperactivated", stop proliferating, and concentrate on killing. Their size and rate of phagocytosis increases—some become large enough to engulf  invading protozoa.[61]

text: In the blood, neutrophils are inactive but are swept along at high speed.  When they receive signals from macrophages at the sites of inflammation, they slow down and leave the blood.   In the tissues, they are activated by cytokines and arrive at the battle scene ready to kill.[62]

text: Migration[edit]

text: When an infection occurs, a chemical "SOS" signal is given off to attract phagocytes to the site.[63] These chemical signals may include proteins from invading bacteria, clotting system peptides, complement products, and cytokines that have been given off by macrophages located in the tissue near the infection site.[2] Another group of chemical attractants are cytokines that recruit neutrophils and monocytes from the blood.[13]

text: To reach the site of infection, phagocytes leave the bloodstream and enter the affected tissues. Signals from the infection cause the endothelial cells that line the blood vessels to make a protein called selectin, which neutrophils stick to on passing by. Other signals called vasodilators loosen the junctions connecting endothelial cells, allowing the phagocytes to pass through the wall. Chemotaxis is the process by which phagocytes follow the cytokine "scent" to the infected spot.[2] Neutrophils travel across epithelial cell-lined organs to sites of infection, and although this is an important component of fighting infection, the migration itself can result in disease-like symptoms.[64] During an infection, millions of neutrophils are recruited from the blood, but they die after a few days.[65]

text: Monocytes[edit]

text: Monocytes develop in the bone marrow and reach maturity in the blood. Mature monocytes have large, smooth, lobed nuclei and abundant cytoplasm that contains granules. Monocytes ingest foreign or dangerous substances and present antigens to other cells of the immune system. Monocytes form two groups: a circulating group and a marginal group that remain in other tissues (approximately 70% are in the marginal group). Most monocytes leave the blood stream after 20–40 hours to travel to tissues and organs and in doing so transform into macrophages[66] or dendritic cells depending on the signals they receive.[67] There are about 500 million monocytes in one litre of human blood.[5]

text: Macrophages[edit]

text: Mature macrophages do not travel far but stand guard over those areas of the body that are exposed to the outside world. There they act as garbage collectors, antigen presenting cells, or ferocious killers, depending on the signals they receive.[68] They derive from monocytes, granulocyte stem cells, or the  cell division of pre-existing macrophages.[69] Human macrophages are about 21 micrometers in diameter.[70]

text: This type of phagocyte does not have granules but contains many lysosomes. Macrophages are found throughout the body in almost all tissues and organs (e.g., microglial cells in the brain and  alveolar macrophages in the lungs), where they silently lie in wait. A macrophage's location can determine its size and appearance. Macrophages  cause inflammation through the production of interleukin-1, interleukin-6, and TNF-alpha.[71] Macrophages are usually only found in tissue and are rarely seen in blood circulation. The life-span of tissue macrophages has been estimated to range from four to fifteen days.[72]

text: Macrophages can be activated to perform functions that a resting monocyte cannot.[71] T helper cells (also known as effector T cells or Th cells), a sub-group of lymphocytes, are responsible for the activation of macrophages. Th1 cells activate macrophages by signaling with IFN-gamma and displaying the protein CD40 ligand.[73] Other signals include TNF-alpha and lipopolysaccharides from bacteria.[71] Th1 cells can recruit other phagocytes to the site of the infection in several ways. They secrete cytokines that act on the bone marrow to stimulate the production of monocytes and neutrophils, and they secrete some of the cytokines that are responsible for the migration of monocytes and neutrophils out of the bloodstream.[74] Th1 cells come from the differentiation of CD4+ T cells once they have responded to antigen in the secondary lymphoid tissues.[71]  Activated macrophages play a potent role in tumor destruction  by producing TNF-alpha, IFN-gamma, nitric oxide, reactive oxygen compounds, cationic proteins, and hydrolytic enzymes.[71]

text: Neutrophils[edit]

text: Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 50% to 60% of the total circulating white blood cells.[75] One litre of human blood contains about five billion neutrophils,[5] which are about 10 micrometers in diameter[76] and live for only about five days.[37] Once they have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection.[77]  They are ferocious eaters and rapidly engulf invaders coated with antibodies and complement, and damaged cells or cellular debris. Neutrophils do not return to the blood; they turn into pus cells and die.[77] Mature neutrophils are smaller than monocytes and have a segmented nucleus with several sections; each section is connected by chromatin filaments—neutrophils can have 2–5 segments. Neutrophils do not normally exit the bone marrow until maturity but during an infection neutrophil precursors called myelocytes and promyelocytes are released.[78]

text: The intra-cellular granules of the human neutrophil have long been recognized for their protein-destroying and bactericidal properties.[79] Neutrophils can  secrete products that stimulate monocytes and macrophages. Neutrophil secretions increase phagocytosis and the formation of reactive oxygen compounds involved in intracellular killing.[80] Secretions from the primary granules of neutrophils stimulate the phagocytosis of IgG-antibody-coated bacteria.[81]

text: Dendritic cells[edit]

text:
Dendritic cells are specialized antigen-presenting cells that have long outgrowths called dendrites,[82] that help to engulf microbes and other invaders.[83][84] Dendritic cells are present in the tissues that are in contact with the external environment, mainly the skin, the inner lining of the nose, the lungs, the stomach, and the intestines.[85] Once activated, they mature and migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and orchestrate the adaptive immune response.[86]
Mature dendritic cells activate  T helper cells and cytotoxic T cells.[87] The activated helper T cells interact with macrophages and B cells to activate them in turn. In addition, dendritic cells can influence the type of immune response produced; when they travel to the lymphoid areas where T cells are held they can activate T cells, which then differentiate into cytotoxic T cells or helper T cells.[83]

text: Mast cells[edit]

text: Mast cells have Toll-like receptors and interact with dendritic cells, B cells, and T cells to help mediate adaptive immune functions.[88] Mast cells express MHC class II molecules and can participate in antigen presentation; however, the mast cell's role in antigen presentation is not very well understood.[89] Mast cells can consume and kill gram-negative bacteria (e.g., salmonella), and process their antigens.[90] They specialize in processing the fimbrial proteins on the surface of bacteria, which are involved in adhesion to tissues.[91][92] In addition to these functions, mast cells produce cytokines that induce an inflammatory response.[93]  This is a vital part of the destruction of microbes because the cytokines attract more phagocytes to the site of infection.[90][94]

text:
Professional Phagocytes[95]

Main location

Variety of phenotypes

Blood

neutrophils, monocytes

Bone marrow

macrophages, monocytes, sinusoidal cells, lining cells

Bone tissue

osteoclasts

Gut and intestinal Peyer's patches

macrophages

Connective tissue

histiocytes, macrophages, monocytes, dendritic cells

Liver

Kupffer cells, monocytes

Lung

self-replicating macrophages, monocytes, mast cells, dendritic cells

Lymphoid tissue

free and fixed macrophages and monocytes, dendritic cells

Nervous tissue

microglial cells (CD4+)

Spleen

free and fixed macrophages, monocytes, sinusoidal cells

Thymus

free and fixed macrophages and monocytes

Skin

resident Langerhans cells, other dendritic cells, conventional macrophages, mast cells

text: Non-professional phagocytes[edit]

text: Dying cells and foreign organisms are consumed by cells other than the "professional" phagocytes.[96] These cells include epithelial cells, endothelial cells, fibroblasts, and mesenchymal cells. They are called non-professional phagocytes, to emphasize that, in contrast to professional phagocytes, phagocytosis is not their principal function.[97] Fibroblasts, for example, which can phagocytose collagen in the process of remolding scars, will also make some attempt to ingest foreign particles.[98]

text: Non-professional phagocytes are more limited than professional phagocytes in the type of particles they can take up. This is due to their lack of efficient phagocytic receptors, in particular opsonins—which are antibodies and complement attached to invaders by the immune system.[11] Additionally, most nonprofessional phagocytes do not produce reactive oxygen-containing molecules in response to phagocytosis.[99]

text:
Non-professional Phagocytes[95]

Main location

Variety of phenotypes

Blood, lymph and lymph nodes

Lymphocytes

Blood, lymph and lymph nodes

NK and LGL cells (large granular lymphocytes)

Skin

Epithelial cells

Blood vessels

Endothelial cells

Connective tissue

Fibroblasts

Blood

Erythrocytes

text: Pathogen evasion and resistance[edit]

text: A pathogen is only successful in infecting an organism if it can get past its defenses. Pathogenic bacteria and protozoa have developed a variety of methods to resist attacks by phagocytes, and many actually survive and replicate within phagocytic cells.[100][101]

text: Avoiding contact[edit]

text: There are several ways bacteria avoid contact with phagocytes. First, they can grow in sites that phagocytes are not capable of traveling to (e.g., the surface of unbroken skin). Second, bacteria can suppress the inflammatory response; without this response to infection phagocytes cannot respond adequately. Third, some species of bacteria can inhibit the ability of phagocytes to travel to the site of infection by interfering with chemotaxis.[100] Fourth, some bacteria can avoid contact with phagocytes by tricking the immune system into "thinking" that the bacteria are "self". Treponema pallidum—the bacterium that causes syphilis—hides from phagocytes by coating its surface with fibronectin,[102] which is  produced naturally by the body and plays a crucial role in wound healing.[103]

text: Avoiding engulfment[edit]

text: Bacteria often produce proteins or sugars that coat their cells and interfere with phagocytosis; these are called capsules.[100] Some examples are the K5 capsule and O75 O antigen found on the surface of Escherichia coli,[104] and the exopolysaccharide capsules of Staphylococcus epidermidis.[105] Streptococcus pneumoniae produces several types of capsule that provide different levels of protection,[106] and group A streptococci produce proteins such as M protein and fimbrial proteins to block engulfment. Some proteins hinder opsonin-related ingestion; Staphylococcus aureus produces Protein A to block antibody receptors, which decreases the effectiveness of opsonins.[107]

text: Survival inside the phagocyte[edit]

text: Bacteria have developed ways to survive inside phagocytes, where they continue to evade the immune system.[108] To get safely inside the phagocyte they  express proteins called invasins. When inside the cell they remain in the cytoplasm and avoid toxic chemicals contained in the phagolysosomes.[109] Some bacteria prevent the fusion of a phagosome and lysosome, to form the phagolysosome.[100] Other pathogens, such as Leishmania, create a highly modified vacuole inside the phagocyte, which helps them persist and replicate.[110] Some bacteria are capable of living inside of the phagolysosome. Staphylococcus aureus, for example, produces the enzymes catalase and superoxide dismutase, which break down chemicals—such as hydrogen peroxide—produced by phagocytes to kill bacteria.[111] Bacteria may escape from the phagosome before the formation of the phagolysosome: Listeria monocytogenes can make a hole in the phagosome wall using enzymes called listeriolysin O and phospholipase C.[112]

text: Killing[edit]

text: Bacteria have developed several ways of killing phagocytes.[107] These include cytolysins, which form pores in the phagocyte's cell membranes, streptolysins and leukocidins, which  cause neutrophils' granules to rupture and release toxic substances,[113][114] and  exotoxins that reduce the supply of a phagocyte's ATP, needed for phagocytosis. After a bacterium is ingested, it may kill the phagocyte by releasing toxins that travel through the phagosome or phagolysosome membrane to target other parts of the cell.[100]

text: Disruption of cell signaling[edit]

text: Some survival strategies often involve disrupting cytokines and other methods of cell signaling to prevent the phagocyte's  responding to invasion.[115] The protozoan parasites Toxoplasma gondii, Trypanosoma cruzi, and Leishmania infect macrophages, and each has a unique way of taming them.[115] Some species of Leishmania alter the infected macrophage's signalling, repress the production of cytokines and microbicidal molecules—nitric oxide and reactive oxygen species—and compromise antigen presentation.[116]

text: Host damage by phagocytes[edit]

text: Macrophages and neutrophils, in particular, play a central role in the inflammatory process by releasing proteins and small-molecule inflammatory mediators that control infection but can damage host tissue. In general, phagocytes aim to destroy pathogens by engulfing them and subjecting them to a battery of toxic chemicals inside a phagolysosome.  If a phagocyte fails to engulf its target, these toxic agents can be released into the environment (an action referred to as "frustrated phagocytosis"). As these agents are also toxic to host cells, they can cause extensive damage to healthy cells and tissues.[117]

text: When neutrophils release their granule contents in the kidney, the contents of the granule (reactive oxygen compounds and proteases) degrade the extracellular matrix of host cells and can cause damage to glomerular cells, affecting their ability to filter blood and causing changes in shape. In addition, phospholipase products (e.g., leukotrienes) intensify the damage. This release of substances promotes chemotaxis of more neutrophils to the site of infection, and glomerular cells can be damaged further by the adhesion molecules during the migration of neutrophils. The injury done to the glomerular cells can cause renal failure.[118]

text: Neutrophils also play a key role in the development of most forms of acute lung injury.[119] Here, activated neutrophils release the contents of their toxic granules into the lung environment.[120] Experiments have shown that a reduction in the number of neutrophils lessens the effects of acute lung injury,[121] but treatment by inhibiting neutrophils is not clinically realistic, as it would leave the host vulnerable to infection.[120] In the liver, damage by neutrophils can contribute to dysfunction and injury in response to the release of endotoxins produced by bacteria, sepsis, trauma, alcoholic hepatitis, ischemia, and hypovolemic shock resulting from acute hemorrhage.[122]

text: Chemicals released by macrophages can also damage host tissue. TNF-α is an important chemical that is released by macrophages that causes the blood in small vessels to clot to prevent an infection from spreading.[123] However, if a bacterial infection spreads to the blood, TNF-α is released into vital organs, which can cause vasodilation and a decrease in plasma volume; these in turn can be followed by septic shock. During septic shock, TNF-α release causes a blockage of the small vessels that supply blood to the vital organs, and the organs may fail. Septic shock can lead to death.[13]

text: Evolutionary origins[edit]

text: Phagocytosis is common and probably appeared early in evolution,[124]  evolving first in unicellular eukaryotes.[125] Amoebae are unicellular protists that separated from the tree leading to metazoa shortly after the divergence of plants, and they share many specific functions with mammalian phagocytic cells.[125] Dictyostelium discoideum, for example, is an amoeba that lives in the soil and feeds on bacteria. Like animal phagocytes, it engulfs bacteria by phagocytosis mainly through Toll-like receptors, and it has other biological functions in common with macrophages.[126] Dictyostelium discoideum is social; it aggregates when starved to form a migrating pseudoplasmodium or slug. This multicellular organism eventually will produce a fruiting body with spores that are resistant to environmental dangers. Before the formation of fruiting bodies, the cells will migrate as a slug-like organism for several days. During this time, exposure to toxins or bacterial pathogens has the potential to compromise survival of the species by limiting spore production. Some of the amoebae engulf bacteria and absorb toxins while circulating within the slug, and these amoebae eventually die. They are genetically identical to the other amoebae in the slug; their self-sacrifice to protect the other amoebae from bacteria is similar to the self-sacrifice of phagocytes seen in the immune system of higher vertebrates. This ancient immune function in social amoebae suggests an evolutionarily conserved cellular foraging mechanism that might have been adapted to defense functions well before the diversification of amoebae into higher forms.[127] However, a common ancestry with mammalian phagocytes has not been proven. Phagocytes occur throughout the animal kingdom,[3] from marine sponges to insects and lower and higher vertebrates.[128][129] The ability of amoebae to distinguish between self and non-self is a pivotal one, and is the root of the immune system of many species of amoeba.[8]


document_title: Beyond the Sea (song)

question_text: who sings the song at the end of finding nemo

root

text: Beyond the Sea (song)

text: Versions[edit]

text:
"Beyond the Sea"
Single by Bobby Darinfrom the album That's AllB-side
"That's the Way Love Is"Released
October 1959Recorded
August 24, 1958Genre
Big bandLength
2:48Label
Atco 6158Songwriter(s)
Jack Lawrence/Charles TrenetBobby Darin singles chronology

"Mack the Knife" (1959)

"Beyond the Sea" (1959)

"Clementine" (1960)

tag: table

text: It has been recorded by many artists, but Bobby Darin's version released in late 1959 is the best known by many, reaching No. 6 on the Billboard Hot 100, No. 15 on the US R&B Chart, and No. 8 in the UK Singles Chart.[2] in early 1960.

tag: p

text: Before Bobby Darin's, two recordings reached the Top 40 of the Billboard Hot 100. Benny Goodman's version charted in 1948, and was featured in the Cary Grant/Betsy Drake romantic comedy Every Girl Should Be Married. Roger Williams' recording reached No. 37 in 1955.[3]

text: Deana Martin recorded Beyond the Sea in 2013. The song was released on her album, Destination Moon, in 2013 by Big Fish Records.

text: American R&B singer George Benson recorded an R&B version of the song under the title "Beyond The Sea (La Mer)." It was released on Warner Bros. This version entered the UK Singles Chart on 20 April 1985. It reached a peak position of no. 60 and remained on the chart for three weeks.[4]

text: The first recording of Beyond the Sea was by Harry James and His Orchestra on December 22, 1947 and the first recording of La Mer was by French jazz musician Roland Gerbeau in December 1945.

text: Other versions[edit]

text:
Django Reinhardt
Gisele MacKenzie
Harry James – Columbia 38134 (1948)
James Melton (1952)
Mantovani
Ray Conniff (1962)
Helen Shapiro on her album A Teenager in Love (1963)
The Sandpipers (on the album Guantanamera as "La Mer (Beyond the Sea)", 1965)
Françoise Hardy (1965)
George Benson (1984)[5]
We Five released a version in 1965 as the B-side of the no. 1 hit "You Were on My Mind".
Royal Crown Revue recorded it in 1998 on the Mugsy's Move album.
Robbie Williams released a version of the song on his album Swing When You're Winning in 2001, which was used in the ending credits for the 2003 Disney·Pixar animated film Finding Nemo.
Will Young winner of Pop Idol performed the song in the semi-final in 2002. Young also recorded the song for the Pop Idol: The Big Band Album featuring The Big Blue.
Kevin Spacey recorded this for the 2004 biopic of Bobby Darin, Beyond the Sea, in which he played the lead role.
Westlife released a version of the song as a digital download release in the UK in 2004.
Barry Manilow released a version on his 2006 album, The Greatest Songs of the Fifties.
Beegie Adair released a version on her 2009 album, Parisian Cafe with David Davidson, violin.
Rod Stewart released a version on his 2010 album, Fly Me to the Moon... The Great American Songbook Volume V.
Celtic Woman released a version on two of their albums, A New Journey and The Greatest Journey: Essential Collection.
Kathryn Williams sang it as the title song for the BBC television series The Café, first screened on Sky 1 in 2011.
Damian McGinty sang his version on the final episode of The Glee Project in August 2011, thus winning a 17 episode arc on the television show Glee.
Jeff Lynne recorded a version for his solo album Long Wave in 2012.
Bobby Caldwell
Pablo Bubar[6] reintroduced "Beyond the Sea" in one of the musical romance sketches of "Pablo the Romantic" from Boom Town, broadcast by BBC Three (UK, 2013). This version included the piano music of Ross Leadbeater.[7]
Deana Martin recorded "Beyond the Sea" on her 2013 album Destination Moon.
Matt Belsante released a version on his 2008 album Blame It on My Youth.

tag: ul

text: In popular culture[edit]

text: Bobby Darin's recording has been used in films, TV shows, and video games, including:

text:
A Life Less Ordinary
Apollo 13
Austin Powers in Goldmember
The X-Files
BioShock
BioShock Infinite: Burial at Sea
Bob's Burgers
Black Rain
Diner
Finding Nemo
Finding Dory
Goodfellas
Lost
The Adventures of Ford Fairlane
White Collar
The Blacklist

text: Kevin Spacey sang the song in the movie Beyond the Sea, a biopic about Bobby Darin, in a "fantasy" sequence leading up to his marriage to Sandra Dee.

text: Robbie Williams sang a version in the closing credits of Finding Nemo.

text: "Beyond the Sea" is the third episode of Generator Rex, the tile character meets a pretty E.V.O. girl called Circe and the two soon forge a connection.

text: This song is used in the trailer for the 2018 film The Meg.


document_title: War Machine (film)

question_text: who does brad pitt play in war machine

question_tokens: who does brad pitt play in war machine

text: War Machine (film)

text: Plot[edit]

text: In the summer of 2009, four-star General Glen McMahon (Brad Pitt), having won renown for his effective leadership in Iraq, is sent to Afghanistan to prepare an assessment so that the government can end the ongoing war.[4][5] He is given wide latitudes to write it, on the sole condition that he not request more troops. McMahon and his staff, particularly his right hand man Major General Greg Pulver (Anthony Michael Hall), are united in their belief that the war can be won, and decide to recommend that President Obama authorize a surge of 40,000 additional troops to secure Helmand province in order to stabilize the country. However, the Secretary of State (Sian Thomas) informs McMahon that his report will not be reviewed until after the upcoming presidential election.

text: Captain Badi Basim (Aymen Hamdouchi), a member of the Afghan National Army, joins McMahon's staff as a "representative" of the Afghan people. He arrives, however, in civilian clothes as he would rather not wear his uniform, which he has in a bag, outside the compound near his home as he walked. Meanwhile, McMahon is informed that, due to alleged irregularities in the counting of votes, a runoff election will have to be held, delaying the review of the assessment further. Fed up, McMahon secretly leaks the assessment to the Washington Post and organizes an interview with 60 Minutes, during which he reveals that, in the last seventy days, he has only been granted one meeting with the President. In response, the government announces that they will send 30,000 troops to Afghanistan, and that all U.S. and coalition forces in the country will leave in 18 months. To gather the remaining 10,000 troops needed for his strategy to work, McMahon and his men head to Paris to negotiate with the other coalition nations.

text: In Paris, McMahon learns that the President is passing through, and wishes to meet with him. The ambassador to Afghanistan (Alan Ruck) warns McMahon that he needs to understand his position: if he continues to anger the President, he will be fired for insubordination. The President, however, merely shakes his hand as he climbs aboard Air Force One due to time constraints, and McMahon and his staff attend a dinner in McMahon's honor, accompanied by Rolling Stone writer Sean Cullen (Scoot McNairy), who intends to write a feature story about his performance for an upcoming issue. The next day, during their anniversary dinner, McMahon's wife Jeanie confronts him about how much time he's spending fighting abroad instead of being with his family back home.

text: While en route to Berlin with McMahon's staff to continue negotiations, Cullen observes their behavior and concludes that they are arrogant and seem to care little about the growing public perception that the war is costly and wasteful. At a conference to discuss his strategy, McMahon is confronted by a German official (Tilda Swinton) who is skeptical of his approach and suggests that McMahon's plans would only lead to more losses. Nevertheless, both the Germans and the French agree to furnish the troops needed for his planned offensive, codenamed "Operation Moshtarak", to begin, with Afghan President Hamid Karzai's (Ben Kingsley) approval.

text: The operation launches, but soon runs into trouble when several civilians are accidentally killed against McMahon's instructions. When he holds a public meeting to explain the incident, the crowd grows hostile and demands that he and his troops leave. Worse, McMahon learns that Cullen's article has been published, and paints a negative picture of him and his staff as openly speaking against the President and mishandling the war effort. Knowing that he will be fired for his actions, McMahon returns to Washington and later takes a job as a civilian consultant.

text: In the aftermath, Cullen ponders the consequences of his article, noting that he wished McMahon's fall would finally convince the government to stop invading foreign countries and end the war in Afghanistan. Instead, however, the government simply assigns a new general to replace McMahon: General Bob White (Russell Crowe).

text: Cast[edit]

text: McMahon's Entourage

text:
Brad Pitt as General Glen McMahon,[6] a character based on General Stanley McChrystal.[7] He is portrayed as an accomplished general with degrees from West Point and Yale[8] brought in to bring a resolution to the conflict in Afghanistan.
Anthony Hayes[9] as Lieutenant Commander Pete Duckman, a Navy SEAL and member of McMahon's staff, possibly based on Navy SEAL David Silverman.
Emory Cohen[10] as Sgt. Willy Dunne, General McMahon's body man.
RJ Cyler as USAF Tech Sgt. Andy Moon, information technology support assistant.[11]
Daniel Betts as USN Rear Admiral Simon Ball, McMahon's Senior Public Affairs Officer.
Topher Grace as Matt Little, a former lobbyist turned McMahon's civilian media adviser.[12]
Anthony Michael Hall as Major General Greg Pulver, ISAF Director of Intelligence,[13] loosely based on Lt. General Michael Flynn.
John Magaro as Colonel Cory Staggart, an Army Ranger and General McMahon's executive officer.[14]
Aymen Hamdouchi as Captain Badi Basim, a scholarly Afghan National Army officer who becomes General McMahon's aide-de-camp.
Scoot McNairy[15] as Sean Cullen, a cynical journalist for Rolling Stone who accompanies McMahon and his staff and acts as narrator throughout the film, loosely based on author Michael Hastings.
Meg Tilly as Jeanie McMahon,[16] McMahon's wife.

text: U.S. Diplomats

text:
Sian Thomas as United States Secretary of State Edith May, based on Hillary Rodham Clinton
Alan Ruck as Pat McKinnon, United States Ambassador to Afghanistan, loosely based on Karl Eikenberry.
Nicholas Jones as Dick Waddle, loosely based on Special Representative for Afghanistan and Pakistan Richard Holbrooke.
Griffin Dunne as Ray Canucci, a United States Department of State senior official.

text: Politicians

text:
Ben Kingsley as President Hamid Karzai[17]
Reggie Brown as President Barack Obama
Tilda Swinton as a German politician

text: Combat Marines

text:
Will Poulter as Sgt. Ricky Ortega, a Marine Corps infantry squad leader.[18]
Lakeith Stanfield as Cpl. Billy Cole, a disillusioned Marine and member of Ortega's squad.[19]
Josh Stewart as Captain Dick North, a Marine Corps officer.

text: Other

text:
Rufus Wright as British Army Lt. Col. Frank Groom
Georgina Rylance as Lydia Cunningham, 60 Minutes journalist.
Russell Crowe[20] as General Bob White (uncredited), General Glen McMahon's replacement similar to David Petraeus.

text: Production[edit]

text: On April 27, 2012, it was announced that New Regency and Plan B Entertainment had acquired the film adaptation rights to the 2011 best seller non-fiction book The Operators by Michael Hastings.[21] On April 14, 2014, David Michôd was hired to write and direct the film based on the war in Afghanistan.[7] Brad Pitt was attached to star as General Stanley McChrystal and produce the film along with his Plan B partners Dede Gardner and Jeremy Kleiner, while the film would be financed by New Regency and RatPac Entertainment.[7]

text: On June 8, 2015, Netflix acquired the distribution rights to the film which was re-titled War Machine, while Ian Bryce also came on board to produce the film along with others.[22] On June 17, The Hollywood Reporter revealed that there had been a budget issue between New Regency and RatPac with producers of Plan B, and thus Netflix had stepped in to buy the distribution rights for $60 million.[1]

text: On August 4, 2015, Emory Cohen was cast in the film to play a member of Gen. McChrystal's staff.[10] On August 10, 2015, Topher Grace joined the film to play Gen. Stanley McChrystal's civilian press adviser.[12] On August 11, 2015, John Magaro signed on to play Cory Burger, a special ops soldier and close advisor to General McMahon.[14] On August 14, 2015, Scoot McNairy joined the cast of the film.[15] On August 19, 2015, Anthony Michael Hall was added to the cast to play General Hank Pulver, loosely based on General Mike Flynn.[13] On August 20, 2015, Keith Stanfield signed on to the film.[19] The same day, Will Poulter also joined the cast for an unspecified role.[18] On August 25, Anthony Hayes joined the film.[9] On October 23, 2015, TheWrap revealed that RJ Cyler had also joined the film.[11] Alan Ruck was spotted filming.[23] Meg Tilly was also spotted but her casting was not then officially confirmed.[16] It was later reported Ben Kingsley and Tilda Swinton had been cast.[24]

text: Filming[edit]

text: Principal photography on the film began in mid-October 2015 in London.[25][26][27] Later on October 19, filming began in Abu Dhabi; the city was transformed into Kabul, streets into a military fortress, an old building as an American Embassy in Kabul, and a street as a Palestinian border crossing.[28][29] Filming also took place at the Abu Dhabi International Airport in November.[29] Some scenes were also filmed at the Dunsfold Aerodrome in Surrey, England.[23] In mid-November 2015, while final scenes were being shot, actors were spotted filming in Ras al-Khaimah and the city's old neighborhood was transformed into Pakistani villages and a military base-camp.[30]

text: Release[edit]

text: The film was released on Netflix on May 26, 2017.[31]

text: Marketing[edit]

text: Brad Pitt visited Mumbai to promote the film and attended a special screening at PVR High Street Phoenix on May 24, 2017.[32] He also met Indian superstar Shah Rukh Khan to promote War Machine.

text: Critical response[edit]

text: On review aggregator website Rotten Tomatoes, the film has an approval rating of 54% based on 73 reviews, and an average rating of 5.8/10. The site's critical consensus reads, "War Machine's uneven execution keeps its fact-based story from cleanly hitting its targets, but those flaws are frequently offset by sharp wit and solid acting."[33] On Metacritic, which assigns a normalized rating, the film has a 56 out of 100 score, based on 30 critics, indicating "mixed or average reviews".[34]


document_title: On the Way to Cape May

question_text: who wrote on the way to cape may

question_tokens: who wrote on the way to cape may

text: On the Way to Cape May

text: "On The Way To Cape May" is a song that has become a Jersey Shore sound summertime anthem for the Philadelphia/Delaware Valley and South Jersey Shore area. It was written by Maurice "Buddy" Nugent according to BMI and The Philadelphia Inquirer. The song became popular without the push of a major record label.

text: Originally, the tune circulated from one band to another around Cape May County in the second half of the 20th century. Early versions came from singers like Daddy Beans and Don Cornell. Cozy Morley advanced its popularity with his large local following. The song became even more locally widespread when Al Alberts recorded it and increased its broadcast exposure on radio and TV.[1] Today, the top selling version is the Philly Cuzz rendition,[citation needed] which has a Bobby Darin inspired arrangement. It has become popular in a variety of 21st century media, such as XM satellite and internet radio, and also enjoys regular airplay on many Delaware Valley AM and FM stations.

text: The lyrics are about a love story and journey which begins with the intro mentioning Ocean City. Traveling southward, the lyrics then continue with mentions of Sea Isle City; Avalon; Stone Harbor; Wildwood coming into view and talks of marriage around the town of Cape May Court House. The words never actually say anything about the town of Cape May. And though that town is the target destination, it's more about a journey through Cape May County.

text: The "Breakfast Club" on 98.1 WOGL plays the Al Alberts version every Friday morning between the Friday preceding Memorial Day through and including the Friday before Labor Day.

text: Harry Kalas, the 2002 Ford C. Frick Award winner honored by the Baseball Hall of Fame, who was the late voice of the Philadelphia Phillies, had an avid affection for this song and can be seen singing the chorus at the end of the WHYY-TV biography produced in 2004.

text: As per the Cape May County Library[edit]

text: "A love story that begins in Ocean City and wends its way along the Jersey Shore through Sea Isle City, Avalon, Stone Harbor, Cape May Court House, Wildwood, and romantic Cape May." (Words and music by Bud Nugent, 1960). Popular comedian Cozy Morley, who owned a nightclub in Wildwood for many years (a life-size statue of him now stands in front of his nightclub), made "On the Way to Cape May" his signature song and performed it many times during his acts in the Philadelphia-South Jersey region. He lived in Collingswood, NJ, for many years and retired to Wildwood.


document_title: Triangular trade

question_text: what did europe trade in the triangular trade

text: Triangular trade

text: Atlantic triangular slave trade[edit]

text:
Part of a series on  Slavery
Contemporary[show]
Child labour
Child soldiers
Conscription
Debt
Forced marriage
Bride buying
Wife selling
Forced prostitution
Human trafficking
Peonage
Penal labour
Sexual slavery
Wage slavery

Historical[show]
Antiquity
Ancient Rome
Babylonia
Ancient Greece
Topics and practices
Atlantic slave trade
Middle Passage
Arab slave trade
Ghilman
Mamluk
Saqaliba
Aztec
Blackbirding
Byzantine Empire
Coolie
Corvée labor
Field slaves in the United States
House slaves
Kholop
Medieval Europe
Panyarring
Thrall
Serfs
History
Russia
Slave market
Slave raiding
Child soldiers
Naval
Galley slave
Impressment
Pirates
Shanghaiing
Slave ship

By country or region[show]
Sub-Saharan Africa
Contemporary Africa
Slavery on the Barbary Coast
Barbary slave trade
Slave Coast
Angola
Chad
Ethiopia
Mali
Mauritania
Niger
Somalia
South Africa
Sudan
Seychelles
North and South America
Americas indigenous
U.S. Natives
Brazil
Lei Áurea
Canada
Caribbean
Barbados
Code Noir
Cuba
Haiti
revolt
Restavek
Latin America
Puerto Rico
Trinidad
United States
colonial
maps
female
partus
penal labor
Slave codes
interregional
Human trafficking
Virgin Islands
Central, East, and South Asia
Human trafficking in Southeast Asia
Bhutan
China
Booi Aha
Laogai
India
Debt bondage
Chukri System
Japan
comfort women
South Korea
Yankee princess
North Korea
Vietnam
Australia and Oceania
Blackbirding in Australia
Human trafficking in Australia
Slave raiding in Easter Island
Human trafficking in Papua New Guinea
Blackbirding in Polynesia
Europe and North Asia
Sex trafficking in Europe
Britain
Denmark
Dutch Republic
Germany in World War II
Malta
Norway
Poland
Portugal
Romania
Russia
Spain
colonies
Sweden
North Africa and West Asia
Iran
Libya
Human trafficking in the Middle East
Ottoman Empire
Yemen

Religion[show]
Bible
Christianity
Catholicism
Mormonism
Islam
21st century
Judaism
Bahá'í Faith

Opposition and resistance[show]
Timeline
Abolitionism
U.K.
U.S.
Anti-Slavery International
Blockade of Africa
U.K.
U.S.
Colonization
Liberia
Sierra Leone
Compensated emancipation
Freedman
manumission
Freedom suit
Abolitionists
Slave Power
Underground Railroad
songs
Slave rebellion
Slave Trade Acts
International law
13th Amendment to the United States Constitution

Related[show]
Common law
Indentured servitude
Unfree labour
Fugitive slaves
laws
Great Dismal Swamp maroons
List of slaves
owners
Slave narrative
films
songs
Slave name
Slave catcher
Slave patrol
Slave Route Project
Treatment in U.S.
breeding
court cases
Washington
Jefferson
Adams
Lincoln
40 acres
Freedmen's Bureau
bit
Emancipation Day
vte

text: The best-known triangular trading system is the transatlantic slave trade, that operated from the late 16th to early 19th centuries, carrying slaves, cash crops, and manufactured goods between West Africa,  Caribbean or American colonies and the European colonial powers, with the northern colonies of British North America, especially New England, sometimes taking over the role of Europe.[1] The use of African slaves was fundamental to growing colonial cash crops, which were exported to Europe. European goods, in turn, were used to purchase African slaves, who were then brought on the sea lane west from Africa to the Americas, the so-called Middle Passage.[2] Despite being driven primarily by economic needs, Europeans sometimes had a religious justification for their actions. In 1452, for instance, Pope Nicholas V, in the Dum Diversas, granted to the kings of Spain and Portugal "full and free permission to invade, search out, capture, and subjugate the Saracens [Muslims] and pagans and any other unbelievers ... and to reduce their persons into perpetual slavery."[3]

text: A classic example is the colonial molasses trade. Sugar (often in its liquid form, molasses) from the Caribbean was traded to Europe or New England, where it was distilled into rum. The profits from the sale of sugar were used to purchase manufactured goods, which were then shipped to West Africa, where they were bartered for slaves. The slaves were then brought back to the Caribbean to be sold to sugar planters. The profits from the sale of the slaves were then used to buy more sugar, which was shipped to Europe, restarting the cycle. The trip itself took five to twelve weeks.

text: The first leg of the triangle was from a European port to Africa, in which ships carried supplies for sale and trade, such as copper, cloth, trinkets, slave beads, guns and ammunition.[4]  When the ship arrived, its cargo would be sold or bartered for slaves. On the second leg, ships made the journey of the Middle Passage from Africa to the New World. Many slaves died of disease in the crowded holds of the slave ships. Once the ship reached the New World, enslaved survivors were sold in the Caribbean or the American colonies. The ships were then prepared to get them thoroughly cleaned, drained, and loaded with export goods for a return voyage, the third leg, to their home port,[5] from the West Indies the main export cargoes were sugar, rum, and molasses; from Virginia, tobacco and hemp. The ship then returned to Europe to complete the triangle.

text: However, because of several disadvantages that slave ships faced compared to other trade ships, they often returned to their home port carrying whatever goods were readily available in the Americas and filled up a large part or all of their capacity with ballast. Other disadvantages include the different form of the ships (to carry as many humans as possible, but not ideal to carry a maximum amount of produce) and the variations in the duration of a slave voyage, making it practically impossible to pre-schedule appointments in the Americas, which meant that slave ships often arrived in the Americas out-of-season.  When the ships did reach their intended ports, only about 90% of the passengers survived the journey across the middle passage.  Due to the slaves being transported in tight, confined spaces, a small percentage of the group that started perished at the hands of disease and lack of nourishment.[6][unreliable source?] Cash crops were transported mainly by a separate fleet which only sailed from Europe to the Americas and back mitigating the impact the slaves involvement brought forth. The Triangular trade is a trade model, not an exact description of the ship's route.[7]

text: A 2017 study provides evidence for the hypothesis that the export of gunpowder technology to Africa increased the transatlantic slave trade by making it easier for Africans to enslave each other: "A one percent increase in gunpowder set in motion a 5-year gun-slave cycle that increased slave exports by an average of 50%, and the impact continued to grow over time."[8]

text: New England[edit]

text:
New England also benefited from the trade, as many merchants from New England, especially the state of Rhode Island, replaced the role of Europe in the triangle. New England also made rum from Caribbean sugar and molasses, which it shipped to Africa as well as within the New World.[9]  Yet, the "triangle trade" as considered in relation to New England was a piecemeal operation. No New England traders are known to have completed a sequential circuit of the full triangle, which took a calendar year on average, according to historian Clifford Shipton.[10] The concept of the New England Triangular trade was first suggested, inconclusively, in an 1866 book by George H. Moore, was picked up in 1872 by historian George C. Mason, and reached full consideration from a lecture in 1887 by American businessman and historian William B. Weeden.[11]
The song "Molasses to Rum" from the musical 1776 vividly describes this form of the triangular trade.

text: Other triangular trades[edit]

text: The term "triangular trade" also refers to a variety of other trades.

text:
A trade pattern which evolved before the American Revolutionary War between Great Britain, the Colonies of British North America, and British colonies in the Caribbean.  This typically involved exporting raw resources, such as fish (especially salt cod), agricultural produce or lumber, from British North American colonies to slaves and planters in the West Indies; sugar and molasses from the Caribbean; and various manufactured commodities from Great Britain.[12]
The shipment of Newfoundland salt cod and corn from Boston in British vessels to southern Europe.[13] This also included the shipment of wine and olive oil to Britain.
A new "sugar triangle" developed in the 1820s and 1830s whereby American ships took local produce to Cuba, then brought sugar or coffee from Cuba to the Baltic coast (Russian Empire and Sweden), then bar iron and hemp back to New England.[14]


document_title: Asteroid belt

question_text: where are s-type asteroids typically found in the solar system

text: Asteroid belt

text: History of observation[edit]

text: In 1596, Johannes Kepler predicted “Between Mars and Jupiter, I place a planet” in his Mysterium Cosmographicum.[13] While analyzing Tycho Brahe's data, Kepler thought that there was too large a gap between the orbits of Mars and Jupiter.[14]

text: In an anonymous footnote to his 1766 translation of Charles Bonnet's Contemplation de la Nature,[15] the astronomer Johann Daniel Titius of Wittenberg[16][17] noted an apparent pattern in the layout of the planets. If one began a numerical sequence at 0, then included 3, 6, 12, 24, 48, etc., doubling each time, and added four to each number and divided by 10, this produced a remarkably close approximation to the radii of the orbits of the known planets as measured in astronomical units provided one allowed for a "missing planet" (equivalent to 24 in the sequence) between the orbits of Mars (12) and Jupiter (48). In his footnote, Titius declared "But should the Lord Architect have left that space empty? Not at all."[16]

text: When William Herschel discovered Uranus in 1781, the planet's orbit matched the law almost perfectly, leading astronomers to conclude that there had to be a planet between the orbits of Mars and Jupiter.

text: On January 1, 1801, Giuseppe Piazzi, chair of astronomy at the University of Palermo, Sicily, found a tiny moving object in an orbit with exactly the radius predicted by this pattern. He dubbed it "Ceres", after the Roman goddess of the harvest and patron of Sicily. Piazzi initially believed it to be a comet, but its lack of a coma suggested it was a planet.[18]

text: Thus, the aforementioned pattern, now known as the Titius–Bode law, predicted the semi-major axes of all eight planets of the time (Mercury, Venus, Earth, Mars, Ceres, Jupiter, Saturn and Uranus).

text: Fifteen months later, Heinrich Olbers discovered a second object in the same region, Pallas. Unlike the other known planets, Ceres and Pallas remained points of light even under the highest telescope magnifications instead of resolving into discs. Apart from their rapid movement, they appeared indistinguishable from stars.

text: Accordingly, in 1802, William Herschel suggested they be placed into a separate category, named "asteroids", after the Greek asteroeides, meaning "star-like".[19][20] Upon completing a series of observations of Ceres and Pallas, he concluded,[21]

text: Neither the appellation of planets nor that of comets, can with any propriety of language be given to these two stars ... They resemble small stars so much as hardly to be distinguished from them. From this, their asteroidal appearance, if I take my name, and call them Asteroids; reserving for myself, however, the liberty of changing that name, if another, more expressive of their nature, should occur.

text: By 1807, further investigation revealed two new objects in the region: Juno and Vesta.[22] The burning of Lilienthal in the Napoleonic wars, where the main body of work had been done,[23] brought this first period of discovery to a close.[22]

text: Despite Herschel's coinage, for several decades it remained common practice to refer to these objects as planets[15] and to prefix their names with numbers representing their date of discovery: 1 Ceres, 2 Pallas, 3 Juno, 4 Vesta. However, in 1845 astronomers detected a fifth object (5 Astraea) and, shortly thereafter, new objects were found at an accelerating rate. Counting them among the planets became increasingly cumbersome. Eventually, they were dropped from the planet list (as first suggested by Alexander von Humboldt in the early 1850s) and Herschel's choice of nomenclature, "asteroids", gradually came into common use.[15]

text: The discovery of Neptune in 1846 led to the discrediting of the Titius–Bode law in the eyes of scientists because its orbit was nowhere near the predicted position. To date, there is no scientific explanation for the law, and astronomers' consensus regards it as a coincidence.[24]

text: The expression "asteroid belt" came into use in the very early 1850s, although it is hard to pinpoint who coined the term. The first English use seems to be in the 1850 translation (by E. C. Otté) of Alexander von Humboldt's Cosmos:[25] "[...] and the regular appearance, about the 13th of November and the 11th of August, of shooting stars, which probably form part of a belt of asteroids intersecting the Earth's orbit and moving with planetary velocity". Another early appearance occurred in Robert James Mann's A Guide to the Knowledge of the Heavens:[26] "The orbits of the asteroids are placed in a wide belt of space, extending between the extremes of [...]". The American astronomer Benjamin Peirce seems to have adopted that terminology and to have been one of its promoters.[27]

text: One hundred asteroids had been located by mid-1868, and in 1891 the introduction of astrophotography by Max Wolf accelerated the rate of discovery still further.[28] A total of 1,000 asteroids had been found by 1921,[29] 10,000 by 1981,[30] and 100,000 by 2000.[31] Modern asteroid survey systems now use automated means to locate new minor planets in ever-increasing quantities.

text: Origin[edit]

text: Formation[edit]

text: In 1802, shortly after discovering Pallas, Olbers suggested to Herschel that Ceres and Pallas were fragments of a much larger planet that once occupied the Mars–Jupiter region, this planet having suffered an internal explosion or a cometary impact many million years before.[32] Over time, however, this hypothesis has fallen from favor. The large amount of energy required to destroy a planet, combined with the belt's low combined mass, which is only about 4% of the mass of the Moon,[2] do not support the hypothesis. Further, the significant chemical differences between the asteroids become difficult to explain if they come from the same planet.[33] Today, most scientists accept that, rather than fragmenting from a progenitor planet, the asteroids never formed a planet at all.

text: In general, in the Solar System, a planetary formation is thought to have occurred via a process comparable to the long-standing nebular hypothesis: a cloud of interstellar dust and gas collapsed under the influence of gravity to form a rotating disc of material that then further condensed to form the Sun and planets.[34] During the first few million years of the Solar System's history, an accretion process of sticky collisions caused the clumping of small particles, which gradually increased in size. Once the clumps reached sufficient mass, they could draw in other bodies through gravitational attraction and become planetesimals. This gravitational accretion led to the formation of the planets.

text: Planetesimals within the region which would become the asteroid belt were too strongly perturbed by Jupiter's gravity to form a planet. Instead, they continued to orbit the Sun as before, occasionally colliding.[35] In regions where the average velocity of the collisions was too high, the shattering of planetesimals tended to dominate over accretion,[36] preventing the formation of planet-sized bodies. Orbital resonances occurred where the orbital period of an object in the belt formed an integer fraction of the orbital period of Jupiter, perturbing the object into a different orbit; the region lying between the orbits of Mars and Jupiter contains many such orbital resonances. As Jupiter migrated inward following its formation, these resonances would have swept across the asteroid belt, dynamically exciting the region's population and increasing their velocities relative to each other.[37]

text: During the early history of the Solar System, the asteroids melted to some degree, allowing elements within them to be partially or completely differentiated by mass. Some of the progenitor bodies may even have undergone periods of explosive volcanism and formed magma oceans. However, because of the relatively small size of the bodies, the period of melting was necessarily brief (compared to the much larger planets), and had generally ended about 4.5 billion years ago, in the first tens of millions of years of formation.[38] In August 2007, a study of zircon crystals in an Antarctic meteorite believed to have originated from 4 Vesta suggested that it, and by extension the rest of the asteroid belt, had formed rather quickly, within ten million years of the Solar System's origin.[39]

text: Evolution[edit]

text: The asteroids are not samples of the primordial Solar System. They have undergone considerable evolution since their formation, including internal heating (in the first few tens of millions of years), surface melting from impacts, space weathering from radiation, and bombardment by micrometeorites.[40] Although some scientists refer to the asteroids as residual planetesimals,[41] other scientists consider them distinct.[42]

text: The current asteroid belt is believed to contain only a small fraction of the mass of the primordial belt. Computer simulations suggest that the original asteroid belt may have contained the mass equivalent to the Earth.[43] Primarily because of gravitational perturbations, most of the material was ejected from the belt within about a million years of formation, leaving behind less than 0.1% of the original mass.[35] Since their formation, the size distribution of the asteroid belt has remained relatively stable: there has been no significant increase or decrease in the typical dimensions of the main-belt asteroids.[44]

text: The 4:1 orbital resonance with Jupiter, at a radius 2.06 AU, can be considered the inner boundary of the asteroid belt. Perturbations by Jupiter send bodies straying there into unstable orbits. Most bodies formed within the radius of this gap were swept up by Mars (which has an aphelion at 1.67 AU) or ejected by its gravitational perturbations in the early history of the Solar System.[45] The Hungaria asteroids lie closer to the Sun than the 4:1 resonance, but are protected from disruption by their high inclination.[46]

text: When the asteroid belt was first formed, the temperatures at a distance of 2.7 AU from the Sun formed a "snow line" below the freezing point of water. Planetesimals formed beyond this radius were able to accumulate ice.[47][48] In 2006 it was announced that a population of comets had been discovered within the asteroid belt beyond the snow line, which may have provided a source of water for Earth's oceans. According to some models, there was insufficient outgassing of water during the Earth's formative period to form the oceans, requiring an external source such as a cometary bombardment.[49]

text: Characteristics[edit]

text: Contrary to popular imagery, the asteroid belt is mostly empty. The asteroids are spread over such a large volume that it would be improbable to reach an asteroid without aiming carefully. Nonetheless, hundreds of thousands of asteroids are currently known, and the total number ranges in the millions or more, depending on the lower size cutoff. Over 200 asteroids are known to be larger than 100 km,[50] and a survey in the infrared wavelengths has shown that the asteroid belt has 0.7–1.7 million asteroids with a diameter of 1 km or more.[51] The apparent magnitudes of most of the known asteroids are 11–19, with the median at about 16.[52]

text: The total mass of the asteroid belt is estimated to be 2.8×1021 to 3.2×1021 kilograms, which is just 4% of the mass of the Moon.[3] The four largest objects, Ceres, 4 Vesta, 2 Pallas, and 10 Hygiea, account for half of the belt's total mass, with almost one-third accounted for by Ceres alone.[4][5]

text: Composition[edit]

text: The current belt consists primarily of three categories of asteroids: C-type or carbonaceous asteroids, S-type or silicate asteroids, and M-type or metallic asteroids.

text: Carbonaceous asteroids, as their name suggests, are carbon-rich. They dominate the asteroid belt's outer regions.[53] Together they comprise over 75% of the visible asteroids. They are redder in hue than the other asteroids and have a very low albedo. Their surface composition is similar to carbonaceous chondrite meteorites. Chemically, their spectra match the primordial composition of the early Solar System, with only the lighter elements and volatiles removed.

text: S-type (silicate-rich) asteroids are more common toward the inner region of the belt, within 2.5 AU of the Sun.[53][54] The spectra of their surfaces reveal the presence of silicates and some metal, but no significant carbonaceous compounds. This indicates that their materials have been significantly modified from their primordial composition, probably through melting and reformation. They have a relatively high albedo and form about 17% of the total asteroid population.

text: M-type (metal-rich) asteroids form about 10% of the total population; their spectra resemble that of iron-nickel. Some are believed to have formed from the metallic cores of differentiated progenitor bodies that were disrupted through collision. However, there are also some silicate compounds that can produce a similar appearance. For example, the large M-type asteroid 22 Kalliope does not appear to be primarily composed of metal.[55] Within the asteroid belt, the number distribution of M-type asteroids peaks at a semi-major axis of about 2.7 AU.[56] It is not yet clear whether all M-types are compositionally similar, or whether it is a label for several varieties which do not fit neatly into the main C and S classes.[57]

text: One mystery of the asteroid belt is the relative rarity of V-type or basaltic asteroids.[59] Theories of asteroid formation predict that objects the size of Vesta or larger should form crusts and mantles, which would be composed mainly of basaltic rock, resulting in more than half of all asteroids being composed either of basalt or olivine. Observations, however, suggest that 99 percent of the predicted basaltic material is missing.[60] Until 2001, most basaltic bodies discovered in the asteroid belt were believed to originate from the asteroid Vesta (hence their name V-type). However, the discovery of the asteroid 1459 Magnya revealed a slightly different chemical composition from the other basaltic asteroids discovered until then, suggesting a different origin.[60] This hypothesis was reinforced by the further discovery in 2007 of two asteroids in the outer belt, 7472 Kumakiri and (10537) 1991 RY16, with a differing basaltic composition that could not have originated from Vesta. These latter two are the only V-type asteroids discovered in the outer belt to date.[59]

text: The temperature of the asteroid belt varies with the distance from the Sun. For dust particles within the belt, typical temperatures range from 200 K (−73 °C) at 2.2 AU down to 165 K (−108 °C) at 3.2 AU[61] However, due to rotation, the surface temperature of an asteroid can vary considerably as the sides are alternately exposed to solar radiation and then to the stellar background.

text: Main-belt comets[edit]

text: Several otherwise unremarkable bodies in the outer belt show cometary activity. Because their orbits cannot be explained through the capture of classical comets, it is thought that many of the outer asteroids may be icy, with the ice occasionally exposed to sublimation through small impacts. Main-belt comets may have been a major source of the Earth's oceans because the deuterium-hydrogen ratio is too low for classical comets to have been the principal source.[62]

text: Orbits[edit]

text: Most asteroids within the asteroid belt have orbital eccentricities of less than 0.4, and an inclination of less than 30°. The orbital distribution of the asteroids reaches a maximum at an eccentricity of around 0.07 and an inclination below 4°.[52] Thus although a typical asteroid has a relatively circular orbit and lies near the plane of the ecliptic, some asteroid orbits can be highly eccentric or travel well outside the ecliptic plane.

text: Sometimes, the term main belt is used to refer only to the more compact "core" region where the greatest concentration of bodies is found. This lies between the strong 4:1 and 2:1 Kirkwood gaps at 2.06 and 3.27 AU, and at orbital eccentricities less than roughly 0.33, along with orbital inclinations below about 20°. As of 2006[update], this "core" region contained 93% of all discovered and numbered minor planets within the Solar System.[63] The JPL Small-Body Database lists 670000+ known main belt asteroids.[64]

text: Kirkwood gaps[edit]

text: The semi-major axis of an asteroid is used to describe the dimensions of its orbit around the Sun, and its value determines the minor planet's orbital period. In 1866, Daniel Kirkwood announced the discovery of gaps in the distances of these bodies' orbits from the Sun. They were located in positions where their period of revolution about the Sun was an integer fraction of Jupiter's orbital period. Kirkwood proposed that the gravitational perturbations of the planet led to the removal of asteroids from these orbits.[65]

text: When the mean orbital period of an asteroid is an integer fraction of the orbital period of Jupiter, a mean-motion resonance with the gas giant is created that is sufficient to perturb an asteroid to new orbital elements. Asteroids that become located in the gap orbits (either primordially because of the migration of Jupiter's orbit,[66] or due to prior perturbations or collisions) are gradually nudged into different, random orbits with a larger or smaller semi-major axis.

text: The gaps are not seen in a simple snapshot of the locations of the asteroids at any one time because asteroid orbits are elliptical, and many asteroids still cross through the radii corresponding to the gaps. The actual spatial density of asteroids in these gaps does not differ significantly from the neighboring regions.[67]

text: The main gaps occur at the 3:1, 5:2, 7:3, and 2:1 mean-motion resonances with Jupiter. An asteroid in the 3:1 Kirkwood gap would orbit the Sun three times for each Jovian orbit, for instance. Weaker resonances occur at other semi-major axis values, with fewer asteroids found than nearby. (For example, an 8:3 resonance for asteroids with a semi-major axis of 2.71 AU.)[68]

text: The main or core population of the asteroid belt is sometimes divided into three zones, based on the most prominent Kirkwood gaps:

text:
Zone I lies between the 4:1 resonance (2.06 AU) and 3:1 resonance (2.5 AU) Kirkwood gaps.
Zone II continues from the end of Zone I out to the 5:2 resonance gap (2.82 AU).
Zone III extends from the outer edge of Zone II to the 2:1 resonance gap (3.28 AU).[69]

text: The asteroid belt may also be divided into the inner and outer belts, with the inner belt formed by asteroids orbiting nearer to Mars than the 3:1 Kirkwood gap (2.5 AU), and the outer belt formed by those asteroids closer to Jupiter's orbit. (Some authors subdivide the inner and outer belts at the 2:1 resonance gap (3.3 AU), whereas others suggest inner, middle, and outer belts; also see diagram).

text: Collisions[edit]

text: The high population of the asteroid belt makes for a very active environment, where collisions between asteroids occur frequently (on astronomical time scales). Collisions between main-belt bodies with a mean radius of 10 km are expected to occur about once every 10 million years.[70] A collision may fragment an asteroid into numerous smaller pieces (leading to the formation of a new asteroid family).[71] Conversely, collisions that occur at low relative speeds may also join two asteroids. After more than 4 billion years of such processes, the members of the asteroid belt now bear little resemblance to the original population.

text: Along with the asteroid bodies, the asteroid belt also contains bands of dust with particle radii of up to a few hundred micrometres. This fine material is produced, at least in part, from collisions between asteroids, and by the impact of micrometeorites upon the asteroids. Due to the Poynting–Robertson effect, the pressure of solar radiation causes this dust to slowly spiral inward toward the Sun.[72]

text: The combination of this fine asteroid dust, as well as ejected cometary material, produces the zodiacal light. This faint auroral glow can be viewed at night extending from the direction of the Sun along the plane of the ecliptic. Asteroid particles that produce the visible zodiacal light average about 40 μm in radius. The typical lifetimes of main-belt zodiacal cloud particles are about 700,000 years. Thus, to maintain the bands of dust, new particles must be steadily produced within the asteroid belt.[72] It was once thought that collisions of asteroids form a major component of the zodiacal light. However, computer simulations by Nesvorný and colleagues attributed 85 percent of the zodiacal-light dust to fragmentations of Jupiter-family comets, rather than to comets and collisions between asteroids in the asteroid belt. At most 10 percent of the dust is attributed to the asteroid belt.[73]

text: Meteorites[edit]

text: Some of the debris from collisions can form meteoroids that enter the Earth's atmosphere.[74] Of the 50,000 meteorites found on Earth to date, 99.8 percent are believed to have originated in the asteroid belt.[75]

text: Families and groups[edit]

text: In 1918, the Japanese astronomer Kiyotsugu Hirayama noticed that the orbits of some of the asteroids had similar parameters, forming families or groups.[76]

text: Approximately one-third of the asteroids in the asteroid belt are members of an asteroid family. These share similar orbital elements, such as semi-major axis, eccentricity, and orbital inclination as well as similar spectral features, all of which indicate a common origin in the breakup of a larger body. Graphical displays of these elements, for members of the asteroid belt, show concentrations indicating the presence of an asteroid family. There are about 20–30 associations that are almost certainly asteroid families. Additional groupings have been found that are less certain. Asteroid families can be confirmed when the members display common spectral features.[77] Smaller associations of asteroids are called groups or clusters.

text: Some of the most prominent families in the asteroid belt (in order of increasing semi-major axes) are the Flora, Eunoma, Koronis, Eos, and Themis families.[56] The Flora family, one of the largest with more than 800 known members, may have formed from a collision less than a billion years ago.[78] The largest asteroid to be a true member of a family (as opposed to an interloper in the case of Ceres with the Gefion family) is 4 Vesta. The Vesta family is believed to have formed as the result of a crater-forming impact on Vesta. Likewise, the HED meteorites may also have originated from Vesta as a result of this collision.[79]

text: Three prominent bands of dust have been found within the asteroid belt. These have similar orbital inclinations as the Eos, Koronis, and Themis asteroid families, and so are possibly associated with those groupings.[80]

text: The main belt evolution after the Late Heavy Bombardment was very likely affected by the passages of large Centaurs and Trans-Neptunian Objecs (TNOs). Centaurs and TNOs that reach the inner Solar System can modify the orbits of main belt asteroids, though only if their mass is of the order of 10−9 m⊙ for single encounters or, one order less in case of multiple close encounters. However Centaurs and TNOs are unlikely to have significantly dispersed young asteroid families in the main belt, but they can have perturbed some old asteroid families. Current main belt asteroids that originated as Centaurs or Trans-Neptunian Objects may lie in the outer belt with short lifetime≤4 My, \ most likely between 2.8 AU and 3.2 AU at larger eccentricities than typical of main belt asteroid.[81]

text: Periphery[edit]

text: Skirting the inner edge of the belt (ranging between 1.78 and 2.0 AU, with a mean semi-major axis of 1.9 AU) is the Hungaria family of minor planets. They are named after the main member, 434 Hungaria; the group contains at least 52 named asteroids. The Hungaria group is separated from the main body by the 4:1 Kirkwood gap and their orbits have a high inclination. Some members belong to the Mars-crossing category of asteroids, and gravitational perturbations by Mars are likely a factor in reducing the total population of this group.[82]

text: Another high-inclination group in the inner part of the asteroid belt is the Phocaea family. These are composed primarily of S-type asteroids, whereas the neighboring Hungaria family includes some E-types.[83] The Phocaea family orbit between 2.25 and 2.5 AU from the Sun.

text: Skirting the outer edge of the asteroid belt is the Cybele group, orbiting between 3.3 and 3.5 AU. These have a 7:4 orbital resonance with Jupiter. The Hilda family orbit between 3.5 and 4.2 AU, and have relatively circular orbits and a stable 3:2 orbital resonance with Jupiter. There are few asteroids beyond 4.2 AU, until Jupiter's orbit. Here the two families of Trojan asteroids can be found, which, at least for objects larger than 1 km, are approximately as numerous as the asteroids of the asteroid belt.[84]

text: New families[edit]

text: Some asteroid families have formed recently, in astronomical terms. The Karin Cluster apparently formed about 5.7 million years ago from a collision with a progenitor asteroid 33 km in radius.[85] The Veritas family formed about 8.3 million years ago; evidence includes interplanetary dust recovered from ocean sediment.[86]

text: More recently, the Datura cluster appears to have formed about 530 thousand years ago from a collision with a main-belt asteroid. The age estimate is based on the probability of the members having their current orbits, rather than from any physical evidence. However, this cluster may have been a source for some zodiacal dust material.[87][88] Other recent cluster formations, such as the Iannini cluster (circa 1–5 million years ago), may have provided additional sources of this asteroid dust.[89]

text: Exploration[edit]

text: The first spacecraft to traverse the asteroid belt was Pioneer 10, which entered the region on 16 July 1972. At the time there was some concern that the debris in the belt would pose a hazard to the spacecraft, but it has since been safely traversed by 12 spacecraft without incident. Pioneer 11, Voyagers 1 and 2 and Ulysses passed through the belt without imaging any asteroids. Galileo imaged 951 Gaspra in 1991 and 243 Ida in 1993, NEAR imaged 253 Mathilde in 1997, Cassini imaged 2685 Masursky in 2000, Stardust imaged 5535 Annefrank in 2002, New Horizons imaged 132524 APL in 2006, Rosetta imaged 2867 Šteins in September 2008 and 21 Lutetia in July 2010, and Dawn orbited Vesta between July 2011 and September 2012 and has orbited Ceres since March 2015.[90] On its way to Jupiter, Juno traversed the asteroid belt without collecting science data.[91] Due to the low density of materials within the belt, the odds of a probe running into an asteroid are now estimated at less than one in a billion.[92]

text: Most belt asteroids imaged to date have come from brief flyby opportunities by probes headed for other targets. Only the Dawn, NEAR and Hayabusa missions have studied asteroids for a protracted period in orbit and at the surface.