Complement system

The complement system known as complement cascade, is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, attack the pathogen's cell membrane. It is part of the innate immune system, not adaptable and does not change during an individual's lifetime; the complement system can, however, be recruited and brought into action by antibodies generated by the adaptive immune system. The complement system consists of a number of small proteins that are synthesized by the liver, circulate in the blood as inactive precursors; when stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, activation of the cell-killing membrane attack complex.

Over 30 proteins and protein fragments make up the complement system, including serum proteins, cell membrane receptors. They account for about 10% of the globulin fraction of blood serum. Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway, the lectin pathway. In 1888, George Nuttall found that sheep blood serum had mild killing activity against the bacterium that causes anthrax; the killing activity disappeared. In 1891, Hans Ernst August Buchner, noting the same property of blood in his experiments, named the killing property "alexin", which means "to ward off" in Greek. By 1894, several laboratories had demonstrated that serum from guinea pigs that had recovered from cholera killed the cholera bacterium in vitro. Heating the serum destroyed its killing activity; the heat-inactivated serum, when injected into guinea pigs exposed to the cholera bacteria, maintained its ability to protect the animals from illness. Jules Bordet, a young Belgian scientist in Paris at the Pasteur Institute, concluded that this principle has two components, one that maintained a "sensitizing" effect after being heated and one whose toxic effect was lost after being heated.

The heat-stable component was responsible for immunity against specific microorganisms, whereas the heat-sensitive component was responsible for the non-specific antimicrobial activity conferred by all normal sera. In 1899, Paul Ehrlich renamed the heat-sensitive component "complement."Ehrlich introduced the term "complement" as part of his larger theory of the immune system. According to this theory, the immune system consists of cells that have specific receptors on their surface to recognize antigens. Upon immunisation with an antigen, more of these receptors are formed, they are shed from the cells to circulate in the blood; those receptors, which we now call "antibodies", were called by Ehrlich "amboceptors" to emphasise their bifunctional binding capacity: They recognise and bind to a specific antigen, but they recognise and bind to the heat-labile antimicrobial component of fresh serum. Ehrlich, named this heat-labile component "complement", because it is something in the blood that "complements" the cells of the immune system.

Ehrlich believed that each antigen-specific amboceptor has its own specific complement, whereas Bordet believed that there is only one type of complement. In the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. Complement triggers the following immune functions: Phagocytosis – by opsonizing antigens. C3b has most important opsonizing activity Inflammation – by attracting macrophages and neutrophils Membrane attack – by rupturing cell wall of bacteria Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes, but significant amounts are produced by tissue macrophages, blood monocytes, epithelial cells of the genitourinary system and gastrointestinal tract. The three pathways of activation all generate homologous variants of the protease C3-convertase; the classical complement pathway requires antigen-antibody complexes for activation, whereas the alternative pathway can be activated by spontaneous complement component 3 hydrolysis, foreign material, pathogens, or damaged cells.

The mannose-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies. In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, causes a cascade of further cleavage and activation events. C3b binds to the surface of pathogens, leading to greater internalization by phagocytic cells by opsonization. In the alternative pathway, C3b binds to Factor B. Factor D releases Factor Ba from Factor B bound to C3b; the complex of C3bBb is a protease which cleaves C5 into C5a. C5 convertase is formed by the classical pathway when C3b binds C4b and C2b. C5a is an important chemotactic protein. C3a is the precursor of an important cytokine named ASP and is rapidly cleaved by carboxypeptidase B. Both C3a and C5a have anaphylatoxin activity, directly triggering degranulation of mast cells as well as increasing vascular permeability and smooth muscle contraction. C5b initiates the membrane attack pathway, which results in the membrane attack complex, consisting of C5b, C6, C7, C8, polymeric C9.

MAC is the cytolytic endproduct of the complement cascade.

Brookfield, Missouri

Brookfield is a city in Linn County, United States. The population was 4,542 at the 2010 census. Brookfield was surveyed in 1859 by a native of Boston. John Wood Brooks is further remembered by the names of four Brookfield streets: John, Wood and Boston streets. A post office called Brookfield has been in operation since 1860. Brookfield is located at 39°46′59″N 93°4′26″W. According to the United States Census Bureau, the city has a total area of 4.29 square miles, of which 4.27 square miles is land and 0.02 square miles is water. As of the census of 2010, there were 4,542 people, 1,892 households, 1,146 families living in the city; the population density was 1,063.7 inhabitants per square mile. There were 2,280 housing units at an average density of 534.0 per square mile. The racial makeup of the city was 95.4% White, 1.3% African American, 0.3% Native American, 0.3% Asian, 0.6% from other races, 2.1% from two or more races. Hispanic or Latino of any race were 2.0% of the population. There were 1,892 households of which 30.8% had children under the age of 18 living with them, 43.3% were married couples living together, 12.5% had a female householder with no husband present, 4.7% had a male householder with no wife present, 39.4% were non-families.

34.5% of all households were made up of individuals and 16.4% had someone living alone, 65 years of age or older. The average household size was 2.32 and the average family size was 2.96. The median age in the city was 40.6 years. 25.8% of residents were under the age of 18. The gender makeup of the city was 54.1 % female. As of the census of 2000, there were 4,769 people, 2,058 households, 1,234 families living in the city; the population density was 1,110.2 people per square mile. There were 2,394 housing units at an average density of 557.3/sq mi. The racial makeup of the city was 96.94% White, 1.26% African American, 0.36% Native American, 0.15% Asian, 0.13% from other races, 1.17% from two or more races. Hispanic or Latino of any race were 0.94% of the population. There were 2,058 households out of which 27.2% had children under the age of 18 living with them, 44.8% were married couples living together, 11.4% had a female householder with no husband present, 40.0% were non-families. 35.3% of all households were made up of individuals and 20.7% had someone living alone, 65 years of age or older.

The average household size was 2.23 and the average family size was 2.86. In the city, the population was spread out with 24.1% under the age of 18, 7.2% from 18 to 24, 23.1% from 25 to 44, 20.8% from 45 to 64, 24.9% who were 65 years of age or older. The median age was 42 years. For every 100 females, there were 83.4 males. For every 100 females age 18 and over, there were 77.9 males. The median income for a household in the city was $25,753, the median income for a family was $32,385. Males had a median income of $23,284 versus $19,004 for females; the per capita income for the city was $14,842. About 14.7% of families and 19.1% of the population were below the poverty line, including 28.7% of those under age 18 and 14.8% of those age 65 or over. Brookfield R-III School District operates one elementary school, one middle school, Brookfield High School, Brookfield Area Career Center; the town has the Brookfield Public Library. Linn County Leader KFMZ 1470, AM KZBK 96.9, FM Every Labor Day weekend, Brookfield hosts the Great Pershing Balloon Derby.

Every fall the Brookfield Bulldogs play the Marceline Tigers in the annual Bell Game, one of the oldest high school football rivalries in the United States. The Bell Game won a USA Today national contest for the nations best football rivalry in 2012; the Bell Game rivalry received 1,761,878 votes and won a $10,000 prize divided between Brookfield and Marceline. Every year Brookfield hosts Twin Parks Summer Festival, a festival that takes place in the Twin Parks and on Main Street; the Twin Parks Summer Festival marks the start of summer for families in and around Brookfield, with activities including craft vendors, a baby contest, a concert on Main Street featuring prominent acts. Damien Boley, Mayor of Smithville, MO. Graduated from Brookfield High School. Doris Akers, gospel singer and composer, was resided there until age five. Akers, an African-American, was inducted into the Gospel Music Hall of Fame in 2001, the Southern Gospel Music Hall of Fame in 2011. Virgil Blossom, Superintendent of Schools of the Little Rock School District during the Little Rock Nine, born in Brookfield in 1906 Jeff Roe, Republican political consultant, was born in Brookfield and lived there until joining the Army at age sixteen.

Punk rock band All lived in Brookfield from 1990–94, when they released their albums Percolater and Breaking Things. Nellie Showalter, an early women's chess champion, was born in Brookfield in 1870. Howard A. Rusk, born in Brookfield on April 9, 1901 and was a prominent physician and founder of the Rusk Institute of Rehabilitation Medicine, he is considered to be the founder of rehabilitation medicine. Don Pratt, the highest-ranking Allied officer killed on D-Day was born here. City of Brookfield Historic maps of Brookfield in the Sanborn Maps of Missouri Collection at the University of Missouri

Mark Hambourg

Mark Hambourg was a Russian-British concert pianist. Mark Hambourg was the eldest son of the pianist Michael Hambourg, was brother of the cellist Boris Hambourg and the violinist Jan Hambourg, of the musical organiser Clement Hambourg, his father was principal of the Voronezh Conservatory, a professor at the Moscow Conservatory, so that Mark continued his studies with his father when he attended that academy. The family moved to London as refugees from the Tsarist regime. There, having been heard by Paderewski, Mark made a debut at the old Princes Hall in July 1890; this was a success, there was another concert there, a tour of the provinces. The family was too poor to turn down these opportunities, though they would gladly have protected the boy from public life; as a child he was billed as Max Hambourg. He was invited into the circle of the painter Felix Moscheles, in London, where he met Oscar Wilde, Bernard Shaw, Ellen Terry and others, it was in this period that he became tired of elderly ladies wanting to kiss him, permitted them to do so only in exchange for a large box of chocolates.

In 1890 Shaw, hearing him play, felt that the Lyric Theatre was exploiting children, but late in 1891 he was admiring his performance of Bach at the Steinway Hall and wrote that, with suitable training, "this Russian lad might astonish the world some day." Sponsored by Paderewski, Hambourg was sent to study under Theodor Leschetitzky in Vienna for three years, arriving there in autumn 1891. There he won the Liszt Scholarship of 500 marks, made a large number of friends among the artistic circles of Vienna, he made his first appearance as an adult pianist in early 1895, playing Chopin's Concerto No. 1 in E minor under the baton of Hans Richter, with the Vienna Philharmonic Orchestra. While still a student with Leschetizky, he stood in at short notice to play Liszt's Hungarian Fantasia under Felix Weingartner, in place of Sophie Menter, indisposed; the audience, at first disappointed, was won over, at the banquet which followed, Brahms himself proposed the toast to the young pianist. In London in 1895 Henry Wood conducted a concert at St James's Hall in which Hambourg played three piano concerti.

According to Wood, his appearance and technique were compared to that of Anton Rubinstein, Ferruccio Busoni told Wood that Hambourg's was the greatest talent of the time. In 1895 Hambourg began his first world tour, beginning in Australia, where in he was asked to prolong his stay by six weeks. Returning to London, he deputized for Paderewski at a Philharmonic Society concert playing Anton Rubinstein's Piano Concerto No. 4 in D minor. He first appeared in Paris in 1896, after that in Brussels and Berlin, he went to the United States in the latter part of 1898, making his New York debut under William Gericke with the Boston Symphony Orchestra, going on to tour the US. He returned to London, in 1901 made his first appearances at the Queen's Hall Proms under Henry Wood. Over the next four years he made another American tour and made visits to Poland and Germany.. In 1906 he made a month-long concert visit to South Africa, taking his own piano by precarious means across the Veldt to one remote location.

He first toured in Canada in 1909 and became friends with the Canadian pianist Harold Bradley. At the outbreak of World War I parts of the press circulated the scurrilous rumour that Hambourg was German, obliging him to prove his Russian origin and to show that he had been naturalized British for over twenty years, he won damages from the Daily Mail in court. Soon afterwards he made another visit to America, narrowly escaped making the return journey on the fateful last voyage of the RMS Lusitania. On his return to London he gave recitals at the Aeolian Hall, of early English music from the Fitzwilliam Virginal Book, learning it by memory from the manuscript itself as the German Breitkopf edition was unavailable, he gave many concerts of classics during the war at the London Coliseum. Hambourg's career survived World War I and he remained a famous performer throughout the 1920s and 1930s. After the war, he again took up his programme of world touring, visiting France, South Africa and Canada, making regular provincial tours in Britain, he made a further world tour before 1924.

Mark Hambourg recorded for HMV and made his first records in 1909. He can be seen in action as the down-and-out pianist nicknamed "Chopin" in John Baxter's 1941 movie The Common Touch. Hambourg married the violinist Dorothea Muir Mackenzie, was father of the pianist Michal Hambourg with whom he sometimes performed piano duos, of Nadine Hambourg Marshall. How to Become a Pianist. From Piano to Forte; the Eighth Octave. Mark Hambourg Collection at the International Piano Archives at Maryland Harriette Brower interview Obituary of Michal Hambourg Biographical essay on Mark and Michal Hambourg by Allan Evans Article on Mark Hambourg by Willa Cather Biographical essay Short biography Bio on the official Hambourg Conservatory of Music website The British Library's online sound recordings of Mark Hambourg Arthur Eaglefield Hull, A Dictionary of Modern Music and Musicians. D. Brook, Masters of the Keyboard (Rockliff, London 1947 (2nd ed