In Greek mythology, Thanatos was the personification of death. He was a minor figure in Greek mythology referred to but appearing in person, his name is transliterated in Latin as Thanatus, but his equivalent in Roman mythology is Mors or Letum. Mors is sometimes erroneously identified with Orcus, whose Greek equivalent was Horkos, God of the Oath; the Greek poet Hesiod established in his Theogony that Thánatos is a son of Nyx and Erebos and twin of Hypnos. Homer confirmed Hypnos and Thanatos as twin brothers in his epic poem, the Iliad, where they were charged by Zeus via Apollo with the swift delivery of the slain hero Sarpedon to his homeland of Lycia. "Then gave him into the charge of swift messengers to carry him, of Hypnos and Thanatos, who are twin brothers, these two presently laid him down within the rich countryside of broad Lycia." Counted among Thanatos' siblings were other negative personifications such as Geras, Moros, Momus, Eris and the Acherousian/Stygian boatman Charon. Thanatos was loosely associated with the three Moirai Atropos, a goddess of death in her own right.
He is occasionally specified as being exclusive to peaceful death, while the bloodthirsty Keres embodied violent death. His duties as a Guide of the Dead were sometimes superseded by Hermes Psychopompos. Conversely, Thanatos may have originated as a mere aspect of Hermes before becoming distinct from him; the god's character is established by Hesiod in the following passage of the Theogony: And there the children of dark Night have their dwellings and Death, awful gods. The glowing Sun never looks upon them with his beams, neither as he goes up into heaven, nor as he comes down from heaven, and the former of them roams peacefully over the earth and the sea's broad back and is kindly to men. Thanatos was thus regarded as merciless and indiscriminate, hated by – and hateful towards — mortals and gods alike, but in myths which feature him, Thanatos could be outwitted, a feat that the sly King Sisyphus of Korinth twice accomplished. When it came time for Sisyphus to die, Zeus ordered Thanatos to chain Sisyphus up in Tartarus.
Sisyphus cheated death by tricking Thanatos into his own shackles, thereby prohibiting the demise of any mortal while Thanatos was so enchained. Ares, the bloodthirsty god of war, grew frustrated with the battles he incited since neither side suffered any casualties, he handed his captor over to the god. Sisyphus would evade Death a second time by convincing Persephone to allow him to return to his wife stating that she never gave him a proper funeral; this time, Sisyphus was forcefully dragged back to the Underworld by Hermes when Sisyphus refused to accept his death. Sisyphus was sentenced to an eternity of frustration in Tartarus where he rolled a boulder up a hill and it would roll back down when he got close to the top. A fragment of Alcaeus, a Greek lyric poet of the 6th century BC, refers to this episode: "King Sisyphos, son of Aiolos, wisest of men, supposed that he was master of Thanatos. Sisyphus, son of Aiolos was a more than mortal figure: for mortals Thanatos presents an inexorable fate, but he was only once overpowered, by the mythical hero Heracles.
Thanatos was consigned to take the soul of Alkestis, who had offered her life in exchange for the continued life of her husband, King Admetos of Pherai. Heracles was an honored guest in the House of Admetos at the time, he offered to repay the king's hospitality by contending with Death itself for Alkestis' life; when Thanatos ascended from Hades to claim Alkestis, Heracles sprung upon the god and overpowered him, winning the right to have Alkestis revived. Thanatos cheated of his quarry. Euripides, in Alcestis: "Thanatos: Much talk. Talking will win you nothing. All the same, the woman goes with me to Hades' house. I go to take her now, dedicate her with my sword, for all whose hair is cut in consecration by this blade's edge are devoted to the gods below." An Orphic Hymn that invoked Thanatos, here given in late 18th century translation: "To Death, Fumigation from Manna. Hear me, O Death, whose empire unconfin'd extends to mortal tribes of ev'ry kind. On thee, the portion of our time depends. Thy sleep perpetual bursts the vivid folds by which the soul, attracting body holds: common to all, of ev'ry sex and age, for nought escapes thy all-destructive rage.
Not youth itself thy clemency can gain and strong, by thee untimely slain. In thee the end of nature's works is known, in thee. No suppliant arts thy dreadful rage controul. O blessed power, regard my ardent prayer, human life to age abundant spare." In eras, as the transition from life to death in Elysium became a more attractive option, Thanatos came to be seen as a beautiful Ephebe. He became associated more with a gentle passing than a woeful demise. Many Roman sarcophagi depict him as a winged boy much akin to Cupid: "Eros with crossed legs and torch reversed became the commonest of all symbols for Death", observes Arthur Bernard Cook. Thanatos has been portrayed as a slumbering infant in the arms of his mother Nyx, or as a youth c
William Cuthbert Faulkner was an American writer and Nobel Prize laureate from Oxford, Mississippi. Faulkner wrote novels, short stories, poetry, a play, he is known for his novels and short stories set in the fictional Yoknapatawpha County, based on Lafayette County, where he spent most of his life. Faulkner is one of the most celebrated writers in American literature and Southern literature specifically. Though his work was published as early as 1919, during the 1920s and 1930s, Faulkner was not known until receiving the 1949 Nobel Prize in Literature, for which he became the only Mississippi-born Nobel winner. Two of his works, A Fable and his last novel The Reivers, won the Pulitzer Prize for Fiction. In 1998, the Modern Library ranked his 1929 novel The Sound and the Fury sixth on its list of the 100 best English-language novels of the 20th century. Absalom, Absalom! Appears on similar lists. Born William Cuthbert Falkner in New Albany, William Faulkner was the first of four sons of Murry Cuthbert Falkner and Maud Butler.
He had three younger brothers: Murry Charles "Jack" Falkner, author John Faulkner, Dean Swift Falkner. Soon after his first birthday, his family moved to Ripley, where his father Murry worked as the treasurer for the family-owned Gulf & Chicago Railroad Company. Murry hoped to inherit the railroad from his father, John Wesley Thompson Falkner, but John had little confidence in Murry's ability to run a business and sold it for $75,000. Following the sale of the railroad business, Murry proposed a plan to get a new start for his family by moving to Texas and becoming a rancher. Maud disagreed with this proposition and they moved instead to Oxford, where Murry's father owned several businesses, making it easy for Murry to find work. Thus, four days prior to William's fifth birthday, the Falkner family settled in Oxford, where he lived on and off for the rest of his life, his family his mother Maud, his maternal grandmother Lelia Butler, Caroline "Callie" Barr crucially influenced the development of Faulkner's artistic imagination.
Both his mother and grandmother were avid readers as well as painters and photographers, educating him in visual language. While Murry enjoyed the outdoors and encouraged his sons to hunt and fish, Maud valued education and took pleasure in reading and going to church, she taught her sons to read before sending them to public school and exposed them to classics such as Charles Dickens and Grimms' Fairy Tales. Faulkner's lifelong education by Callie Barr is central to his novels' preoccupations with the politics of sexuality and race; as a schoolchild, Faulkner had success early on. He excelled in the first grade, skipped the second, did well through the third and fourth grades. However, beginning somewhere in the fourth and fifth grades of his schooling, Faulkner became a much quieter and more withdrawn child, he began to play hooky and became somewhat indifferent to his schoolwork, instead taking interest in studying the history of Mississippi on his own time beginning in the seventh grade. The decline of his performance in school continued, Faulkner wound up repeating the eleventh and twelfth grade, never graduating from high school.
Faulkner spent his boyhood listening to stories told to him by his elders including those of the Civil War, the Ku Klux Klan, the Falkner family. Faulkner's grandfather would tell him of the exploits of William's great-grandfather and namesake, William Clark Falkner, a successful businessman and Civil War hero. Telling stories about "Old Colonel", as his family called him, had become something of a family pastime when Faulkner was a boy. According to one of Faulkner's biographers, by the time William was born, his great-grandfather had "been enshrined long since as a household deity."When he was 17, Faulkner met Philip Stone, who became an important early influence on his writing. Stone came from one of Oxford's older families. Faulkner attended the latter, joined the Sigma Alpha Epsilon fraternity, pursued his dream to become a writer. Stone read and was impressed by some of Faulkner's early poetry, becoming one of the first to recognize and encourage Faulkner's talent. Stone mentored the young Faulkner, introducing him to the works of writers such as James Joyce, who influenced Faulkner's own writing.
In his early 20s, Faulkner gave poems and short stories he had written to Stone in hopes of their being published. Stone would in turn send these to publishers; the younger Faulkner was influenced by the history of his family and the region in which he lived. Mississippi marked his sense of humor, his sense of the tragic position of "black and white" Americans, his characterization of Southern characters, his timeless themes, including fiercely intelligent people dwelling behind the façades of good ol' boys and simpletons. Unable to join the United States Army due to his height, Faulkner enlisted in a reservist unit of the British Army in Toronto. Despite his claims, records indicate that Faulkner was never a member of the British Royal Flying Corps and never saw service during the First World War. In 19
Medical ethics is a system of moral principles that apply values to the practice of clinical medicine and in scientific research. Medical ethics is based on a set of values that professionals can refer to in the case of any confusion or conflict; these values include the respect for autonomy, non-maleficence and justice. Such tenets may allow doctors, care providers, families to create a treatment plan and work towards the same common goal, it is important to note that these four values are not ranked in order of importance or relevance and that they all encompass values pertaining to medical ethics. However, a conflict may arise leading to the need for hierarchy in an ethical system, such that some moral obligations overrule others with the purpose of applying the best moral judgement to a difficult medical situation. There are several codes of conduct; the Hippocratic Oath discusses basic principles for medical professionals. This document dates back to the fifth century BCE. Both The Declaration of Helsinki and The Nuremberg Code are two well-known and well respected documents contributing to medical ethics.
Other important markings in the history of Medical Ethics include Roe v. Wade in 1973 and the development of Hemodialysis in the 1960s. More new techniques for gene editing aiming at treating and curing diseases utilizing gene editing, are raising important moral questions about their applications in medicine and treatments as well as societal impacts on future generations. An example if this is CRISPR/Cas9 being considered as a therapeutic tool; as this field continues to develop and change throughout history, the focus remains on fair and moral thinking. Medical ethics encompasses a practical application in clinical settings as well as scholarly work on its history and sociology; the term medical ethics first dates back to 1803, when English author and physician Thomas Percival published a document describing the requirements and expectations of medical professionals within medical facilities. The Code of Ethics was adapted in 1847, relying on Percival's words. Over the years in 1903, 1912, 1947, revisions have been made to the original document.
The practice of Medical Ethics is accepted and practiced throughout the world. Western medical ethics may be traced to guidelines on the duty of physicians in antiquity, such as the Hippocratic Oath, early Christian teachings; the first code of medical ethics, Formula Comitis Archiatrorum, was published in the 5th century, during the reign of the Ostrogothic king Theodoric the Great. In the medieval and early modern period, the field is indebted to Islamic scholarship such as Ishaq ibn Ali al-Ruhawi, Avicenna's Canon of Medicine and Muhammad ibn Zakariya ar-Razi, Jewish thinkers such as Maimonides, Roman Catholic scholastic thinkers such as Thomas Aquinas, the case-oriented analysis of Catholic moral theology; these intellectual traditions continue in Catholic and Jewish medical ethics. By the 18th and 19th centuries, medical ethics emerged as a more self-conscious discourse. In England, Thomas Percival, a physician and author, crafted the first modern code of medical ethics, he drew up a pamphlet with the code in 1794 and wrote an expanded version in 1803, in which he coined the expressions "medical ethics" and "medical jurisprudence".
However, there are some who see Percival's guidelines that relate to physician consultations as being excessively protective of the home physician's reputation. Jeffrey Berlant is one such critic who considers Percival's codes of physician consultations as being an early example of the anti-competitive, "guild"-like nature of the physician community. In addition, since the mid 19th century up to the 20th century, physician-patient relationships that once were more familiar became less prominent and less intimate, sometimes leading to malpractice, which resulted in less public trust and a shift in decision making power from the paternalistic physician model to today's emphasis on patient autonomy and self-determination. In 1815, the Apothecaries Act was passed by the Parliament of the United Kingdom, it introduced compulsory apprenticeship and formal qualifications for the apothecaries of the day under the license of the Society of Apothecaries. This was the beginning of regulation of the medical profession in the UK.
In 1847, the American Medical Association adopted its first code of ethics, with this being based in large part upon Percival's work. While the secularized field borrowed from Catholic medical ethics, in the 20th century a distinctively liberal Protestant approach was articulated by thinkers such as Joseph Fletcher. In the 1960s and 1970s, building upon liberal theory and procedural justice, much of the discourse of medical ethics went through a dramatic shift and reconfigured itself into bioethics. Well-known medical ethics cases include: Albert Kligman's dermatology experiments Deep sleep therapy Doctors' Trial Greenberg v. Miami Children's Hospital Research Institute Henrietta Lacks Chester M. Southam's Cancer Injection Study Human radiation experiments Jesse Gelsinger Moore v. Regents of the University of California Surgical removal of body parts to try to improve mental health Medical Experimentation on Black Americans Milgram experiment Radioactive iodine experiments The Monster Study Plutonium injections The David Reimer case The Stanford Prison Experiment Tuskegee syphilis experiment Willowbrook State School Yanomami blood sample collection Darkness in El DoradoSince the 1970s, the growing influence of ethics in contemporary medicine can be seen in the increasing use of Institutional Review Boards to evaluate experimen
Fascination with death
Fascination with death has occurred throughout human history, characterized by obsessions with death and all things related to death and the afterlife. In past times, people would form cults around death and figures. Famously, Osiris, La Santa Muerte have all had large cult followings. La Santa Muerte, or the personification of death, is worshiped by many in Mexico and other countries in Central America. Day of the Dead is a celebration for the dead; the ancient Egyptians are most famous for their fascination of death by mummifying their dead and building exquisite tombs, like the pyramids of Giza, for their dead. Many of their deities were death-related, such as: the devourer of unworthy souls; the Greek underworld, was ruled by the god Hades, had five rivers that flowed through it. The rivers were: river of sadness; the Underworld had attendants who, though not rulers, were important beings. The Furies were female spirits. Keres were female spirits of destruction. Persephone was the spouse of Hades.
Thanatos, the god of death, was said to wear dark robes. The Vikings believed that if a warrior died in battle, he would be taken to the Norse afterlife: the hall of Valhöll, in which the warriors would prepare for Ragnarökk, the battle at the end of the world. Rune stones were erected to commemorate brave warriors. Death in one's sleep was considered dishonorable. In the early part of the 20th century, it was common to hold séances at dinner parties. A séance is an event where a group of people try to communicate with the dead through one person of the group, known as a psychic medium. Today there are a number of authors. "If it bleeds, it leads" is a phrase related to this, meaning that in the mass media most of the material is based on death. For example: death and crime are always a topic in the news; the goth and metal subcultures are associated with death and dying. Daniel Kahneman and others have studied the psychology behind this. For example, people buy insurance and make other decisions based on what comes to mind—e.g.
The recorded high-water mark for a flood considering that something worse is possible and in many cases likely. This interacts with the management policies of media outlets to create availability cascades and media feeding frenzies: For example, "strokes cause twice as many deaths as all accidents combined, but 80% of respondents judged accidental death to be more likely.... Coverage is itself biased toward poignancy; the media do not just shape what the public is interested in, but are shaped by it."This fascination with death and interaction with media editorial policies sometimes has problematic consequences for public policy. For example, Vincent Sacco and others described how the mainstream commercial media in the United States changed their editorial policies in the 1970s to focus more on the police blotter; the human psychology behind "If it bleeds, it leads" meant they could retain or increase their audience while reducing the cost of producing the news: Investigative journalism is enormously expensive if it offends a major advertiser.
Focusing on crimes committed by people without substantive political or economic power is cheap. The resulting increase in crime stories convinced the US electorate; this led to the election of politicians who would "get tough on crime." The result was a five-fold increase in the United States incarceration rate not justified by any actual increase in crime.'Necrophilia' is used in English to refer to the paraphilia associated with dead bodies, although the term has been used in a broader sense and in foreign language to refer to'a fascination with death.' Thanatology "Death: A User's Guide" by Tom Hickman "Spook: Science Tackles The Afterlife" by Mary Roach "Letters from the Afterlife: A Guide to the Other Side" by Katherine Hart, Elsa Barker "Life After Death: A History of the Afterlife in Western Religion" by Alan F. Segal "The Ghost Next Door" by Mark Alan Morris "Ghosts and Hauntings" by Patricia Telesco "The Beginner's Guide for the Recently Deceased" by David Staume "Walt Disney's Curious Fascination With Death" by Sean Braswell All Souls Day Day of the Dead History and Customs of Halloween Dark Tourism - the pursuit of visiting sites where people have died
Social science is a category of academic disciplines, concerned with society and the relationships among individuals within a society. Social science as a whole has many branches; these social sciences include, but are not limited to: anthropology, communication studies, history, human geography, linguistics, political science, public health, sociology. The term is sometimes used to refer to the field of sociology, the original "science of society", established in the 19th century. For a more detailed list of sub-disciplines within the social sciences see: Outline of social science. Positivist social scientists use methods resembling those of the natural sciences as tools for understanding society, so define science in its stricter modern sense. Interpretivist social scientists, by contrast, may use social critique or symbolic interpretation rather than constructing empirically falsifiable theories, thus treat science in its broader sense. In modern academic practice, researchers are eclectic, using multiple methodologies.
The term "social research" has acquired a degree of autonomy as practitioners from various disciplines share in its aims and methods. The history of the social sciences begins in the Age of Enlightenment after 1650, which saw a revolution within natural philosophy, changing the basic framework by which individuals understood what was "scientific". Social sciences came forth from the moral philosophy of the time and were influenced by the Age of Revolutions, such as the Industrial Revolution and the French Revolution; the social sciences developed from the sciences, or the systematic knowledge-bases or prescriptive practices, relating to the social improvement of a group of interacting entities. The beginnings of the social sciences in the 18th century are reflected in the grand encyclopedia of Diderot, with articles from Jean-Jacques Rousseau and other pioneers; the growth of the social sciences is reflected in other specialized encyclopedias. The modern period saw "social science" first used as a distinct conceptual field.
Social science was influenced by positivism, focusing on knowledge based on actual positive sense experience and avoiding the negative. Auguste Comte used the term "science sociale" to describe the field, taken from the ideas of Charles Fourier. Following this period, there were five paths of development that sprang forth in the social sciences, influenced by Comte on other fields. One route, taken was the rise of social research. Large statistical surveys were undertaken in various parts of the United States and Europe. Another route undertaken was initiated by Émile Durkheim, studying "social facts", Vilfredo Pareto, opening metatheoretical ideas and individual theories. A third means developed, arising from the methodological dichotomy present, in which social phenomena were identified with and understood; the fourth route taken, based in economics, was developed and furthered economic knowledge as a hard science. The last path was the correlation of knowledge and social values. In this route and prescription were non-overlapping formal discussions of a subject.
Around the start of the 20th century, Enlightenment philosophy was challenged in various quarters. After the use of classical theories since the end of the scientific revolution, various fields substituted mathematics studies for experimental studies and examining equations to build a theoretical structure; the development of social science subfields became quantitative in methodology. The interdisciplinary and cross-disciplinary nature of scientific inquiry into human behaviour and environmental factors affecting it, made many of the natural sciences interested in some aspects of social science methodology. Examples of boundary blurring include emerging disciplines like social research of medicine, neuropsychology and the history and sociology of science. Quantitative research and qualitative methods are being integrated in the study of human action and its implications and consequences. In the first half of the 20th century, statistics became a free-standing discipline of applied mathematics.
Statistical methods were used confidently. In the contemporary period, Karl Popper and Talcott Parsons influenced the furtherance of the social sciences. Researchers continue to search for a unified consensus on what methodology might have the power and refinement to connect a proposed "grand theory" with the various midrange theories that, with considerable success, continue to provide usable frameworks for massive, growing data banks; the social sciences will for the foreseeable future be composed of different zones in the research of, sometime distinct in approach toward, the field. The term "social science" may refer either to the specific sciences of society established by thinkers such as Comte, Durkheim and Weber, or more to all disciplines outside of "noble science" and arts. By the late 19th century, the academic social sciences were constituted of five fields: jurisprudence and amendment of the law, health and trade, art. Around the start of the 21st century, the expanding domain of economics in the social sciences has been described as economic imperialism.
The social science disciplines are branches of knowledge taught and researched at the college or university level. Social science disciplines are defined and rec
Archaeology, or archeology, is the study of human activity through the recovery and analysis of material culture. The archaeological record consists of artifacts, biofacts or ecofacts and cultural landscapes. Archaeology can be considered a branch of the humanities. In North America archaeology is a sub-field of anthropology, while in Europe it is viewed as either a discipline in its own right or a sub-field of other disciplines. Archaeologists study human prehistory and history, from the development of the first stone tools at Lomekwi in East Africa 3.3 million years ago up until recent decades. Archaeology is distinct from palaeontology, the study of fossil remains, it is important for learning about prehistoric societies, for whom there may be no written records to study. Prehistory includes over 99% of the human past, from the Paleolithic until the advent of literacy in societies across the world. Archaeology has various goals, which range from understanding culture history to reconstructing past lifeways to documenting and explaining changes in human societies through time.
The discipline involves surveying and analysis of data collected to learn more about the past. In broad scope, archaeology relies on cross-disciplinary research, it draws upon anthropology, art history, ethnology, geology, literary history, semiology, textual criticism, information sciences, statistics, paleography, paleontology and paleobotany. Archaeology developed out of antiquarianism in Europe during the 19th century, has since become a discipline practiced across the world. Archaeology has been used by nation-states to create particular visions of the past. Since its early development, various specific sub-disciplines of archaeology have developed, including maritime archaeology, feminist archaeology and archaeoastronomy, numerous different scientific techniques have been developed to aid archaeological investigation. Nonetheless, archaeologists face many problems, such as dealing with pseudoarchaeology, the looting of artifacts, a lack of public interest, opposition to the excavation of human remains.
The science of archaeology grew out of the older multi-disciplinary study known as antiquarianism. Antiquarians studied history with particular attention to ancient artifacts and manuscripts, as well as historical sites. Antiquarianism focused on the empirical evidence that existed for the understanding of the past, encapsulated in the motto of the 18th-century antiquary, Sir Richard Colt Hoare, "We speak from facts not theory". Tentative steps towards the systematization of archaeology as a science took place during the Enlightenment era in Europe in the 17th and 18th centuries. In Europe, philosophical interest in the remains of Greco-Roman civilization and the rediscovery of classical culture began in the late Middle Age. Flavio Biondo, an Italian Renaissance humanist historian, created a systematic guide to the ruins and topography of ancient Rome in the early 15th century, for which he has been called an early founder of archaeology. Antiquarians of the 16th century, including John Leland and William Camden, conducted surveys of the English countryside, drawing and interpreting the monuments that they encountered.
One of the first sites to undergo archaeological excavation was Stonehenge and other megalithic monuments in England. John Aubrey was a pioneer archaeologist who recorded numerous megalithic and other field monuments in southern England, he was ahead of his time in the analysis of his findings. He attempted to chart the chronological stylistic evolution of handwriting, medieval architecture and shield-shapes. Excavations were carried out by the Spanish military engineer Roque Joaquín de Alcubierre in the ancient towns of Pompeii and Herculaneum, both of, covered by ash during the Eruption of Mount Vesuvius in AD 79; these excavations began in 1748 in Pompeii, while in Herculaneum they began in 1738. The discovery of entire towns, complete with utensils and human shapes, as well the unearthing of frescos, had a big impact throughout Europe. However, prior to the development of modern techniques, excavations tended to be haphazard; the father of archaeological excavation was William Cunnington. He undertook excavations in Wiltshire from around 1798.
Cunnington made meticulous recordings of Neolithic and Bronze Age barrows, the terms he used to categorize and describe them are still used by archaeologists today. One of the major achievements of 19th-century archaeology was the development of stratigraphy; the idea of overlapping strata tracing back to successive periods was borrowed from the new geological and paleontological work of scholars like William Smith, James Hutton and Charles Lyell. The application of stratigraphy to archaeology first took place with the excavations of prehistorical and Bronze Age sites. In the third and fourth decades of the 19th-century, archaeologists like Jacques Boucher de Perthes and Christian Jürgensen Thomsen began to put the artifacts they had found in chronological order. A major figure in the development of archaeology into a rigorous science was the army officer and ethnologist, Augustus Pitt Rivers, who began excavations on his land in England in the 1880s, his approach was methodical by the standards of the time, he is regarded as the first scientific archaeologist.
He arranged his artifacts by type or "typologically, within types by date or "chronologically"
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages and dendritic cells. A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes; the lysosomes contain hydrolytic enzymes and reactive oxygen species which kill and digest the pathogens. Phagosomes can form in non-professional phagocytes, but they can only engulf a smaller range of particles, do not contain ROS; the useful materials from the digested particles are moved into the cytosol, waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens. However, some bacteria can exploit phagocytosis as an invasion strategy, they either reproduce inside of the phagolysosome or escape into the cytoplasm before the phagosome fuses with the lysosome.
Many Mycobacteria, including Mycobacterium tuberculosis and Mycobacterium avium paratuberculosis, can manipulate the host macrophage to prevent lysosomes from fusing with phagosomes and creating mature phagolysosomes. Such incomplete maturation of the phagosome maintains an environment favorable to the pathogens inside it. Phagosomes are large enough to degrade whole bacteria, or apoptotic and senescent cells, which are >0.5μm in diameter. This means a phagosome is several orders of magnitude bigger than an endosome, measured in nanometres. Phagosomes are formed when pathogens or opsonins bind to a transmembrane receptor, which are randomly distributed on the phagocyte cell surface. Upon binding, "outside-in" signalling triggers actin polymerisation and pseudopodia formation, which surrounds and fuses behind the microorganism. Protein kinase C, phosphoinositide 3-kinase, phospholipase C are all needed for signalling and controlling particle internalisation. More cell surface receptors can bind to the particle in a zipper-like mechanism as the pathogen is surrounded, increasing the binding avidity.
Fc receptor, complement receptors, mannose receptor and Dectin-1 are phagocytic receptors, which means that they can induce phagocytosis if they are expressed in non-phagocytic cells such as fibroblasts. Other proteins such as Toll-like receptors are involved in pathogen pattern recognition and are recruited to phagosomes but do not trigger phagocytosis in non-phagocytic cells, so they are not considered phagocytic receptors. Opsonins are molecular tags such as antibodies and complements that attach to pathogens and up-regulate phagocytosis. Immunoglobulin G is the major type of antibody present in the serum, it is part of the adaptive immune system, but it links to the innate response by recruiting macrophages to phagocytose pathogens. The antibody binds to microbes with the variable Fab domain, the Fc domain binds to Fc receptors to induce phagocytosis. Complement-mediated internalisation has much less significant membrane protrusions, but the downstream signalling of both pathways converge to activate Rho GTPases.
They control actin polymerisation, required for the phagosome to fuse with endosomes and lysosomes. Other non-professional phagocytes have some degree of phagocytic activity, such as thyroid and bladder epithelial cells that can engulf erythrocytes and retinal epithelial cells that internalise retinal rods; however non-professional phagocytes do not express specific phagocytic receptors such as FcR and have a much lower rate of internalisation. Some invasive bacteria can induce phagocytosis in non-phagocytic cells to mediate host uptake. For example, Shigella can secrete toxins that alter the host cytoskeleton and enter the basolateral side of enterocytes; as the membrane of the phagosome is formed by the fusion of the plasma membrane, the basic composition of the phospholipid bilayer is the same. Endosomes and lysosomes fuse with the phagosome to contribute to the membrane when the engulfed particle is big, such as a parasite, they deliver various membrane proteins to the phagosome and modify the organelle structure.
Phagosomes can engulf artificial low-density latex beads and purified along a sucrose concentration gradient, allowing the structure and composition to be studied. By purifying phagosomes at different time points, the maturation process can be characterised. Early phagosomes are characterised by Rab5, which transition into Rab7 as the vesicle matures into late phagosomes; the nascent phagosome is not inherently bactericidal. As it matures, it becomes more acidic from pH 6.5 to pH 4, gains characteristic protein markers and hydrolytic enzymes. The different enzymes function at various optimal pH, forming a range so they each work in narrow stages of the maturation process. Enzyme activity can be fine-tuned by allowing for greater flexibility; the phagosome moves along microtubules of the cytoskeleton, fusing with endosomes and lysosomes sequentially in a dynamic "kiss-and-run" manner. This intracellular transport depends on the size of the phagosomes. Larger organelles are transported persistently from the cell periphery towards the perinuclear region whereas smaller organelles are transported more bidirectionally back and forth between cell center and cell periphery.
Vacuolar proton pumps are delivered to the phagosome to acidify the organelle compartment, creating a more hostile environment for pathogens and facilitating protein degradation. The bacterial proteins are denatured in low pH and become more