document_title: Alternating current

question_text: who developed the first alternating current electric system

text: Alternating current

text: Transmission, distribution, and domestic power supply[edit]

text:
Electrical energy is distributed as alternating current because AC voltage may be increased or decreased with a transformer. This allows the power to be transmitted through power lines efficiently at high voltage, which reduces the energy lost as heat due to resistance of the wire, and transformed to a lower, safer, voltage for use. Use of a higher voltage leads to significantly more efficient transmission of power. The power losses (

P

L

{\displaystyle P_{\rm {L}}}

) in a conductor are a product of the square of the current (I) and the resistance (R) of the conductor, described by the formula

text: This means that when transmitting a fixed power on a given wire, if the current is halved (i.e. the voltage is doubled), the power loss will be four times less.

text: The power transmitted is equal to the product of the current and the voltage (assuming no phase difference); that is,

text: Consequently, power transmitted at a higher voltage requires less loss-producing current than for the same power at a lower voltage. Power is often transmitted at hundreds of kilovolts, and transformed to 100 V – 240 V for domestic use.

text: High voltages have disadvantages, such as the increased insulation required, and generally increased difficulty in their safe handling. In a power plant, energy is generated at a convenient voltage for the design of a generator, and then stepped up to a high voltage for transmission. Near the loads, the transmission voltage is stepped down to the voltages used by equipment. Consumer voltages vary somewhat depending on the country and size of load, but generally motors and lighting are built to use up to a few hundred volts between phases. The voltage delivered to equipment such as lighting and motor loads is standardized, with an allowable range of voltage over which equipment is expected to operate. Standard power utilization voltages and percentage tolerance vary in the different mains power systems found in the world. High-voltage direct-current (HVDC) electric power transmission systems have become more viable as technology has provided efficient means of changing the voltage of DC power. HVDC systems, however, tend to be more expensive and less efficient over shorter distances than transformers.[citation needed] Transmission with high voltage direct current was not feasible in the early days of electric power transmission, as there was then no economically viable way to step down the voltage of DC for end user applications such as lighting incandescent bulbs.

text: Three-phase electrical generation is very common. The simplest way is to use three separate coils in the generator stator, physically offset by an angle of 120° (one-third of a complete 360° phase) to each other. Three current waveforms are produced that are equal in magnitude and 120° out of phase to each other. If coils are added opposite to these (60° spacing), they generate the same phases with reverse polarity and so can be simply wired together. In practice, higher "pole orders" are commonly used. For example, a 12-pole machine would have 36 coils (10° spacing). The advantage is that lower rotational speeds can be used to generate the same frequency. For example, a 2-pole machine running at 3600 rpm and a 12-pole machine running at 600 rpm produce the same frequency; the lower speed is preferable for larger machines. If the load on a three-phase system is balanced equally among the phases, no current flows through the neutral point. Even in the worst-case unbalanced (linear) load, the neutral current will not exceed the highest of the phase currents. Non-linear loads (e.g. the switch-mode power supplies widely used) may require an oversized neutral bus and neutral conductor in the upstream distribution panel to handle harmonics. Harmonics can cause neutral conductor current levels to exceed that of one or all phase conductors.

text: For three-phase at utilization voltages a four-wire system is often used. When stepping down three-phase, a transformer with a Delta (3-wire) primary and a Star (4-wire, center-earthed) secondary is often used so there is no need for a neutral on the supply side. For smaller customers (just how small varies by country and age of the installation) only a single phase and neutral, or two phases and neutral, are taken to the property. For larger installations all three phases and neutral are taken to the main distribution panel. From the three-phase main panel, both single and three-phase circuits may lead off. Three-wire single-phase systems, with a single center-tapped transformer giving two live conductors, is a common distribution scheme for residential and small commercial buildings in North America. This arrangement is sometimes incorrectly referred to as "two phase". A similar method is used for a different reason on construction sites in the UK. Small power tools and lighting are supposed to be supplied by a local center-tapped transformer with a voltage of 55 V between each power conductor and earth. This significantly reduces the risk of electric shock in the event that one of the live conductors becomes exposed through an equipment fault whilst still allowing a reasonable voltage of 110 V between the two conductors for running the tools.

text: A third wire, called the bond (or earth) wire, is often connected between non-current-carrying metal enclosures and earth ground. This conductor provides protection from electric shock due to accidental contact of circuit conductors with the metal chassis of portable appliances and tools. Bonding all non-current-carrying metal parts into one complete system ensures there is always a low electrical impedance path to ground sufficient to carry any fault current for as long as it takes for the system to clear the fault. This low impedance path allows the maximum amount of fault current, causing the overcurrent protection device (breakers, fuses) to trip or burn out as quickly as possible, bringing the electrical system to a safe state. All bond wires are bonded to ground at the main service panel, as is the neutral/identified conductor if present.

text: AC power supply frequencies[edit]

text: The frequency of the electrical system varies by country and sometimes within a country; most electric power is generated at either 50 or 60 hertz. Some countries have a mixture of 50 Hz and 60 Hz supplies, notably electricity power transmission in Japan. A low frequency eases the design of electric motors, particularly for hoisting, crushing and rolling applications, and commutator-type traction motors for applications such as railways. However, low frequency also causes noticeable flicker in arc lamps and incandescent light bulbs. The use of lower frequencies also provided the advantage of lower impedance losses, which are proportional to frequency. The original Niagara Falls generators were built to produce 25 Hz power, as a compromise between low frequency for traction and heavy induction motors, while still allowing incandescent lighting to operate (although with noticeable flicker). Most of the 25 Hz residential and commercial customers for Niagara Falls power were converted to 60 Hz by the late 1950s, although some[which?] 25 Hz industrial customers still existed as of the start of the 21st century. 16.7 Hz power (formerly 16 2/3 Hz) is still used in some European rail systems, such as in Austria, Germany, Norway, Sweden and Switzerland. Off-shore, military, textile industry, marine, aircraft, and spacecraft applications sometimes use 400 Hz, for benefits of reduced weight of apparatus or higher motor speeds. Computer mainframe systems were often powered by 400 Hz or 415 Hz for benefits of ripple reduction while using smaller internal AC to DC conversion units.[3] In any case, the input to the M-G set is the local customary voltage and frequency, variously 200 V (Japan), 208 V, 240 V (North America), 380 V, 400 V or 415 V (Europe), and variously 50 Hz or 60 Hz.

text: Effects at high frequencies[edit]

text: A direct current flows uniformly throughout the cross-section of a uniform wire. An alternating current of any frequency is forced away from the wire's center, toward its outer surface. This is because the acceleration of an electric charge in an alternating current produces waves of electromagnetic radiation that cancel the propagation of electricity toward the center of materials with high conductivity. This phenomenon is called skin effect. At very high frequencies the current no longer flows in the wire, but effectively flows on the surface of the wire, within a thickness of a few skin depths. The skin depth is the thickness at which the current density is reduced by 63%. Even at relatively low frequencies used for power transmission (50 Hz – 60 Hz), non-uniform distribution of current still occurs in sufficiently thick conductors. For example, the skin depth of a copper conductor is approximately 8.57 mm at 60 Hz, so high current conductors are usually hollow to reduce their mass and cost. Since the current tends to flow in the periphery of conductors, the effective cross-section of the conductor is reduced. This increases the effective AC resistance of the conductor, since resistance is inversely proportional to the cross-sectional area. The AC resistance often is many times higher than the DC resistance, causing a much higher energy loss due to ohmic heating (also called I2R loss).

text: Techniques for reducing AC resistance[edit]

text: For low to medium frequencies, conductors can be divided into stranded wires, each insulated from one another, and the relative positions of individual strands specially arranged within the conductor bundle. Wire constructed using this technique is called Litz wire. This measure helps to partially mitigate skin effect by forcing more equal current throughout the total cross section of the stranded conductors. Litz wire is used for making high-Q inductors, reducing losses in flexible conductors carrying very high currents at lower frequencies, and in the windings of devices carrying higher radio frequency current (up to hundreds of kilohertz), such as switch-mode power supplies and radio frequency transformers.

text: Techniques for reducing radiation loss[edit]

text: As written above, an alternating current is made of electric charge under periodic acceleration, which causes radiation of electromagnetic waves. Energy that is radiated is lost. Depending on the frequency, different techniques are used to minimize the loss due to radiation.

text: Twisted pairs[edit]

text: At frequencies up to about 1 GHz, pairs of wires are twisted together in a cable, forming a twisted pair. This reduces losses from electromagnetic radiation and inductive coupling. A twisted pair must be used with a balanced signalling system, so that the two wires carry equal but opposite currents. Each wire in a twisted pair radiates a signal, but it is effectively cancelled by radiation from the other wire, resulting in almost no radiation loss.

text: Coaxial cables[edit]

text: Coaxial cables are commonly used at audio frequencies and above for convenience. A coaxial cable has a conductive wire inside a conductive tube, separated by a dielectric layer. The current flowing on the surface of the inner conductor is equal and opposite to the current flowing on the inner surface of the outer tube. The electromagnetic field is thus completely contained within the tube, and (ideally) no energy is lost to radiation or coupling outside the tube. Coaxial cables have acceptably small losses for frequencies up to about 5 GHz. For microwave frequencies greater than 5 GHz, the losses (due mainly to the electrical resistance of the central conductor) become too large, making waveguides a more efficient medium for transmitting energy. Coaxial cables with an air rather than solid dielectric are preferred as they transmit power with lower loss.

text: Waveguides[edit]

text: Waveguides are similar to coaxial cables, as both consist of tubes, with the biggest difference being that the waveguide has no inner conductor. Waveguides can have any arbitrary cross section, but rectangular cross sections are the most common. Because waveguides do not have an inner conductor to carry a return current, waveguides cannot deliver energy by means of an electric current, but rather by means of a guided electromagnetic field. Although surface currents do flow on the inner walls of the waveguides, those surface currents do not carry power. Power is carried by the guided electromagnetic fields. The surface currents are set up by the guided electromagnetic fields and have the effect of keeping the fields inside the waveguide and preventing leakage of the fields to the space outside the waveguide. Waveguides have dimensions comparable to the wavelength of the alternating current to be transmitted, so they are only feasible at microwave frequencies. In addition to this mechanical feasibility, electrical resistance of the non-ideal metals forming the walls of the waveguide cause dissipation of power (surface currents flowing on lossy conductors dissipate power). At higher frequencies, the power lost to this dissipation becomes unacceptably large.

text: Fiber optics[edit]

text: At frequencies greater than 200 GHz, waveguide dimensions become impractically small, and the ohmic losses in the waveguide walls become large. Instead, fiber optics, which are a form of dielectric waveguides, can be used. For such frequencies, the concepts of voltages and currents are no longer used.

text: Mathematics of AC voltages[edit]

text: Alternating currents are accompanied (or caused) by alternating voltages. An AC voltage v can be described mathematically as a function of time by the following equation:

text: where

text:
V

p
e
a
k

{\displaystyle \displaystyle V_{\rm {peak}}}

 is the peak voltage (unit: volt),

ω

{\displaystyle \displaystyle \omega }

 is the angular frequency (unit: radians per second)

The angular frequency is related to the physical frequency,

f

{\displaystyle \displaystyle f}

 (unit = hertz), which represents the number of cycles per second, by the equation

ω
=
2
π
f

{\displaystyle \displaystyle \omega =2\pi f}

.

t

{\displaystyle \displaystyle t}

 is the time (unit: second).

text:
The peak-to-peak value of an AC voltage is defined as the difference between its positive peak and its negative peak. Since the maximum value of

sin

(
x
)

{\displaystyle \sin(x)}

 is +1 and the minimum value is −1, an AC voltage swings between

+

V

p
e
a
k

{\displaystyle +V_{\rm {peak}}}

 and

−

V

p
e
a
k

{\displaystyle -V_{\rm {peak}}}

. The peak-to-peak voltage, usually written as

V

p
p

{\displaystyle V_{\rm {pp}}}

 or

V

P
−
P

{\displaystyle V_{\rm {P-P}}}

, is therefore

V

p
e
a
k

−
(
−

V

p
e
a
k

)
=
2

V

p
e
a
k

{\displaystyle V_{\rm {peak}}-(-V_{\rm {peak}})=2V_{\rm {peak}}}

.

text: Power[edit]

text: The relationship between voltage and the power delivered is

text:
Rather than using instantaneous power,

p
(
t
)

{\displaystyle p(t)}

, it is more practical to use a time averaged power (where the averaging is performed over any integer number of cycles). Therefore, AC voltage is often expressed as a root mean square (RMS) value, written as

V

r
m
s

{\displaystyle V_{\rm {rms}}}

, because

text: Root mean square voltage[edit]

text: Below it is assumed an AC waveform (with no DC component).

text:
For an arbitrary periodic waveform

v
(
t
)

{\displaystyle v(t)}

 of period

T

{\displaystyle T}

:

text: For a sinusoidal voltage:

text: For a triangle waveform centered about zero

text: For a square waveform centered about zero

text: Example[edit]

text: To illustrate these concepts, consider a 230 V AC mains supply used in many countries around the world. It is so called because its root mean square value is 230 V. This means that the time-averaged power delivered is equivalent to the power delivered by a DC voltage of 230 V. To determine the peak voltage (amplitude), we can rearrange the above equation to:

text:
For 230 V AC, the peak voltage

V

p
e
a
k

{\displaystyle V_{\mathrm {peak} }}

 is therefore

230
V
×

2

{\displaystyle 230V\times {\sqrt {2}}}

, which is about 325 V. During the course of one cycle the voltage rises from zero to 325 V, falls through zero to -325 V, and returns to zero.

text: Information transmission[edit]

text: Alternating current is used to transmit information, as in the cases of telephone and cable television. Information signals are carried over a wide range of AC frequencies. POTS telephone signals have a frequency of about 3 kHz, close to the baseband audio frequency. Cable television and other cable-transmitted information currents may alternate at frequencies of tens to thousands of megahertz. These frequencies are similar to the electromagnetic wave frequencies often used to transmit the same types of information over the air.

text: History[edit]

text: The first alternator to produce alternating current was a dynamo electric generator based on Michael Faraday's principles constructed by the French instrument maker Hippolyte Pixii in 1832.[4] Pixii later added a commutator to his device to produce the (then) more commonly used direct current. The earliest recorded practical application of alternating current is by Guillaume Duchenne, inventor and developer of electrotherapy. In 1855, he announced that AC was superior to direct current for electrotherapeutic triggering of muscle contractions.[5] Alternating current technology had first developed in Europe due to the work of Guillaume Duchenne (1850s), the Hungarian Ganz Works company (1870s), and in the 1880s: Sebastian Ziani de Ferranti, Lucien Gaulard, and Galileo Ferraris.

text: In 1876, Russian engineer Pavel Yablochkov invented a lighting system where sets of induction coils were installed along a high voltage AC line. Instead of changing voltage, the primary windings transferred power to the secondary windings which were connected to one or several 'electric candles' (arc lamps) of his own design,[6][7] used to keep the failure of one lamp from disabling the entire circuit.[6] In 1878, the Ganz factory, Budapest, Hungary, began manufacturing equipment for electric lighting and, by 1883, had installed over fifty systems in Austria-Hungary. Their AC systems used arc and incandescent lamps, generators, and other equipment.[8]

text: Transformers[edit]

text: Alternating current systems can use transformers to change voltage from low to high level and back, allowing generation and consumption at low voltages but transmission, possibly over great distances, at high voltage, with savings in the cost of conductors and energy losses. A bipolar open-core power transformer developed by Lucien Gaulard and John Dixon Gibbs was demonstrated in London in 1881, and attracted the interest of Westinghouse. They also exhibited the invention in Turin in 1884. However these early induction coils with open magnetic circuits are inefficient at transferring power to loads. Until about 1880, the paradigm for AC power transmission from a high voltage supply to a low voltage load was a series circuit. Open-core transformers with a ratio near 1:1 were connected with their primaries in series to allow use of a high voltage for transmission while presenting a low voltage to the lamps. The inherent flaw in this method was that turning off a single lamp (or other electric device) affected the voltage supplied to all others on the same circuit. Many adjustable transformer designs were introduced to compensate for this problematic characteristic of the series circuit, including those employing methods of adjusting the core or bypassing the magnetic flux around part of a coil.[9] The direct current systems did not have these drawbacks, giving it significant advantages over early AC systems.

text: Pioneers[edit]

text: In the autumn of 1884, Károly Zipernowsky, Ottó Bláthy and Miksa Déri (ZBD), three engineers associated with the Ganz factory, determined that open-core devices were impractical, as they were incapable of reliably regulating voltage.[10] In their joint 1885 patent applications for novel transformers (later called ZBD transformers), they described two designs with closed magnetic circuits where copper windings were either a wound around iron wire ring core or b) surrounded by iron wire core.[9] In both designs, the magnetic flux linking the primary and secondary windings traveled almost entirely within the confines of the iron core, with no intentional path through air (see toroidal cores). The new transformers were 3.4 times more efficient than the open-core bipolar devices of Gaulard and Gibbs.[11] The Ganz factory in 1884 shipped the world's first five high-efficiency AC transformers.[12] This first unit had been manufactured to the following specifications: 1,400 W, 40 Hz, 120:72 V, 11.6:19.4 A, ratio 1.67:1, one-phase, shell form.[12]

text: The ZBD patents included two other major interrelated innovations: one concerning the use of parallel connected, instead of series connected, utilization loads, the other concerning the ability to have high turns ratio transformers such that the supply network voltage could be much higher (initially 1400 V to 2000 V) than the voltage of utilization loads (100 V initially preferred).[13][14] When employed in parallel connected electric distribution systems, closed-core transformers finally made it technically and economically feasible to provide electric power for lighting in homes, businesses and public spaces.[15][16] The other essential milestone was the introduction of 'voltage source, voltage intensive' (VSVI) systems'[17] by the invention of constant voltage generators in 1885.[18] Ottó Bláthy also invented the first AC electricity meter.[19][20][21][22]

text: The AC power systems was developed and adopted rapidly after 1886 due to its ability to distribute electricity efficiently over long distances, overcoming the limitations of the direct current system. In 1886, the ZBD engineers designed the world's first power station that used AC generators to power a parallel-connected common electrical network, the steam-powered Rome-Cerchi power plant.[23] The reliability of the AC technology received impetus after the Ganz Works electrified a large European metropolis: Rome in 1886.[23]

text: In the UK, Sebastian de Ferranti, who had been developing AC generators and transformers in London since 1882, redesigned the AC system at the Grosvenor Gallery power station in 1886 for the London Electric Supply Corporation (LESCo) including alternators of his own design and transformer designs similar to Gaulard and Gibbs.[24] In 1890 he designed their power station at Deptford[25] and converted the Grosvenor Gallery station across the Thames into an electrical substation, showing the way to integrate older plants into a universal AC supply system.[26]

text: In the US William Stanley, Jr. designed one of the first practical devices to transfer AC power efficiently between isolated circuits. Using pairs of coils wound on a common iron core, his design, called an induction coil, was an early (1885) transformer. Stanley also worked on engineering and adapting European designs such as the Gaulard and Gibbs transformer for US entrepreneur George Westinghouse who started building AC systems in 1886. The spread of Westinghouse and other AC systems triggered a push back in late 1887 by Edison (a proponent of direct current) who attempted to discredit alternating current as too dangerous in a public campaign called the "War of Currents". In 1888 alternating current systems gained further viability with introduction of a functional AC motor, something these systems had lacked up till then. The design, an induction motor, was independently invented by Galileo Ferraris and Nikola Tesla (with Tesla's design being licensed by Westinghouse in the US). This design was further developed into the modern practical three-phase form by Mikhail Dolivo-Dobrovolsky and Charles Eugene Lancelot Brown.[27]

text: The Ames Hydroelectric Generating Plant (spring of 1891) and the original Niagara Falls Adams Power Plant (August 25, 1895) were among the first hydroelectric alternating current power plants. The first long distance transmission of single-phase electricity was from a hydroelectric generating plant in Oregon at Willamette Falls which in 1890 sent power fourteen miles downriver to downtown Portland for street lighting.[28] In 1891, a second transmission system was installed in Telluride Colorado.[29] The San Antonio Canyon Generator was the third commercial single-phase hydroelectric AC power plant in the United States to provide long-distance electricity. It was completed on December 31, 1892 by Almarian William Decker to provide power to the city of Pomona, California which was 14 miles away. In 1893 he next designed the first commercial three-phase power plant in the United States using alternating current was the hydroelectric Mill Creek No. 1 Hydroelectric Plant near Redlands, California. Decker's design incorporated 10 kV three-phase transmission and established the standards for the complete system of generation, transmission and motors used today. The Jaruga Hydroelectric Power Plant in Croatia was set in operation on 28 August 1895. The two generators (42 Hz, 550 kW each) and the transformers were produced and installed by the Hungarian company Ganz. The transmission line from the power plant to the City of Šibenik was 11.5 kilometers (7.1 mi) long on wooden towers, and the municipal distribution grid 3000 V/110 V included six transforming stations. Alternating current circuit theory developed rapidly in the latter part of the 19th and early 20th century. Notable contributors to the theoretical basis of alternating current calculations include Charles Steinmetz, Oliver Heaviside, and many others.[30][31] Calculations in unbalanced three-phase systems were simplified by the symmetrical components methods discussed by Charles Legeyt Fortescue in 1918.


document_title: Madden NFL

question_text: what is the newest madden game for ps4

question_tokens: what is the newest madden game for ps4

root

text: Madden NFL

text: Overview[edit]

text:
“
A computer is a helluva lot smarter than me.
”

— John Madden, 2014[2]

tag: table

text: As of 2013[update] Electronic Arts has sold more than 100 million copies of Madden NFL, and more than five million in one year, for more than $4 billion in total sales.[3] At EA Tiburon in Orlando, Florida a team of 30 developers and more than 100 game testers works on each new game in the series,[4] which as of 2012[update] contains more than 10 million lines of source code.[5]

tag: p

text: Madden, once better known for Ace Hardware commercials than football despite winning Super Bowl XI with the Oakland Raiders, is now better known for Madden NFL than as coach or broadcaster.[6][4] He receives an estimated $2 to 3 million each year for his endorsement[7] but describes himself as "never a good player" of Madden, and prefers to watch others play.[5] Although Madden says that "a computer is a helluva lot smarter than me"[2] he has influenced the series' design from the first game, and since retiring from broadcasting and doing videogame voice commentary in 2009 his participation in each Madden's development has increased:[5][4]

text: He breaks down upcoming rules changes. He brings up concussions, helmet-to-helmet hits and gimmick quarterbacks. A digression on how the Dome Patrol-era Saints used to frustrate Bill Walsh's 49ers teams with short linebacker drops becomes a lecture on the obsolescence of the fullback, which then morphs into a short aside on player character.[4]

text:
"Madden recalls a time in San Francisco when a Philadelphia Eagles player rushed into a hotel room asking, 'Where's Madden?' When people pointed to the Fox commentator, the player said, 'No, not that Madden. I want the game!'"

—Los Angeles Times, 2002[8]

tag: div

text: EA estimates that the series has five to seven million dedicated fans, and an underground circuit of Madden cash tournaments exists.[5] Marshall Faulk in 2010 estimated that "50 percent on up" of NFL players are Madden players, who play in the league with or against childhood heroes they once chose to play as in the game.[9] Players typically play as themselves regardless of their electronic counterparts' abilities[8][10][9] and immediately check new releases of the game for changes in the more than 60 ratings of their talent.[11][2] They often complain to Madden and EA about allegedly inaccurate ratings (only Emmitt Smith has told him that the game rated him too high), or ask for changes in their in-game appearance. Such complaints began as early as 1990, confusing the broadcaster, who did not contribute the player statistics for that year's version due to lack of time.[4][7]

text: Coaches and players at all levels of the sport say that Madden has influenced them, and recommend the game to learn football strategy and tactics, practice plays and assignments, and simulate opponents.[4][9] Young players who grew up with it reportedly understand plays better than those who did not. Wired in 2010 attributed the growing use of rookie quarterbacks and the spread offense to the game, stating that "the sport is being taken over by something you might call Maddenball — a sophisticated, high-scoring, pass-happy, youth-driven phenomenon". When the Denver Broncos' Brandon Stokley in 2009 burned six seconds of the clock with an unusual run before scoring the winning touchdown against the Cincinnati Bengals, Madden designers—who were watching the game with Madden—immediately recognized his action as "what happens in the game!"[9][4]

text: Football broadcasts on television use Madden-like visual cues to more closely resemble it, and the NFL considers the series its "33rd franchise" because each week during the season EA Sports receives the same searchable film database of every play that each of the league's 32 teams do.[5][2] The game is the NFL's second-largest source of licensing revenue after apparel, and an important part of the league's recruitment of children as new football fans.[8]

text: The Pro Football Hall of Fame in 2003 opened an interactive exhibit in which visitors play Madden,[11] three years before its namesake's induction.[4] Museum of the Moving Image in New York City in early 2014 celebrated Madden NFL's 25th anniversary, with an exhibit including five playable versions of the game.[12]

text: Voice commentary[edit]

text: Voice commentary in Madden allows players or watchers to hear the game being called as if it were a real game on TV.[13] For early versions of the game, this commentary was performed by Madden himself and his play-by-play partner. Initially, this was Pat Summerall, his partner during their days at the CBS and the Fox from the early 1980s to the early 2000s until Summerall retired; the role was then filled by Al Michaels, John's broadcast partner on ABC Monday Night Football (2002–2005) and NBC Sunday Night Football (2006–2008). For the first Madden games on the Xbox 360 and PS3, they featured a generic EA Sports radio announcer doing play-by-play. This started with Madden 06 and ended with Madden 08.[14] Other versions of those games still featured Madden's commentary. Madden NFL 09 would end up being the last version to feature Madden's commentary, albeit in a reduced role. By that time, he felt that reciting a script covering every single scenario in the game was boring and tedious[15]—Madden recalled the long hours spent alone in the recording studio as "the most difficult part of any part that I've ever had in the game and the least amount of fun"[5]—but said that in the decision to remove him from game commentary, "I feel that something is being taken away from me".[4]

text: Madden and Michaels were replaced by Cris Collinsworth as color commentator and Tom Hammond on play-by-play in Madden NFL 09 and Madden NFL 10. Gus Johnson replaced Hammond in Madden NFL 11 and Madden NFL 12, with Collinsworth handling color commentary in both games.[16] Madden NFL 13 marked the debut of real-life announcing team Jim Nantz and Phil Simms, including them appearing in an in-booth cutscene before the game.[17] Nantz and Simms stayed until Madden NFL 16, when they were replaced by Brandon Gaudin and Charles Davis for Madden NFL 17. Gaudin and Davis returned to the studio throughout the 2016–17 NFL season to add new commentary relevant to each week of the season.[18]

text: In a similar approach used by the automobile industry, until Madden NFL 25, the Madden series has always historically been numbered one year later than the year in which it is released. However, the season it represents is the year in which the game is released (thus, Madden NFL 13 was actually released in 2012 and is modeled after the 2012 NFL season).

text: Series overview[edit]

text:
Titles in the series

Title
Release year
PC
4th gen
5th gen
6th gen
7th gen
8th gen
Handheld
Other platforms
Notes
On the cover

John Madden Football
1988
MS-DOS

C=64/C=128, Apple II

John Madden

John Madden Football
1990

Genesis, SNES

Amiga

John Madden

John Madden Football II
1991
MS-DOS

John Madden

John Madden Football '92
1991

Genesis

John Madden

John Madden Football '93
1992

Genesis, SNES

John Madden

John Madden Duo CD Football
1993

TG16 (Super CD)

John Madden

Madden NFL '94
1993

Genesis, SNES

John Madden

John Madden Football[19][20]
1994

3DO

John Madden

Madden NFL '95
1994

Genesis, SNES

Game Boy, Game Gear, TV game

John Madden with Erik Williams of the Dallas Cowboys and Karl Wilson of the San Francisco 49ers in the background

Madden NFL '96
1995
Windows
Genesis, SNES

Game Boy, Game Gear

John Madden

Madden NFL 97
1996
Windows
Genesis, SNES
PS, Saturn

Game Boy

John Madden with Cary Brabham of the Carolina Panthers and Gordon Laro of the Jacksonville Jaguars in the background[21]

Madden Football 64
1997

N64

John Madden

Madden NFL 98
1997
Windows
Genesis, SNES
PS, Saturn

John Madden

Madden NFL 99
1998
Windows

PS, N64

John Madden / Garrison Hearst of the San Francisco 49ers (PAL version)

Madden NFL 2000
1999
Windows

PS, N64

Game Boy Color
Macintosh

John Madden with Barry Sanders of the Detroit Lions in the background / Dorsey Levens of the Green Bay Packers (European PAL version)

Madden NFL 2001
2000
Windows

PS, N64
PS2

Game Boy Color

Eddie George of the Tennessee Titans

Madden NFL 2002
2001
Windows

PS, N64
PS2, GCN, Xbox

Game Boy Color, Game Boy Advance

Daunte Culpepper of the Minnesota Vikings

Madden NFL 2003
2002
Windows

PS
PS2, NGC, Xbox

Game Boy Advance

Marshall Faulk of the St. Louis Rams

Madden NFL 2004
2003
Windows

PS
PS2, NGC, Xbox

Game Boy Advance

Michael Vick of the Atlanta Falcons

Madden NFL 2005
2004
Windows

PS
PS2, NGC, Xbox

Game Boy Advance, Nintendo DS, Tapwave Zodiac

Ray Lewis of the Baltimore Ravens

Madden NFL 06
2005
Windows

PS2, NGC, Xbox
Xbox 360

Game Boy Advance, Nintendo DS, PSP, Windows Mobile, Mobile phone

Donovan McNabb of the Philadelphia Eagles

Madden NFL 07
2006
Windows

PS2, NGC, Xbox
Xbox 360, PS3, Wii

Game Boy Advance, Nintendo DS, PSP

Shaun Alexander of the Seattle Seahawks

Madden NFL 08
2007
Windows

PS2, NGC, Xbox
Xbox 360, PS3, Wii

Nintendo DS, PSP
Mac OS X

Vince Young of the Tennessee Titans / Luis Castillo of the San Diego Chargers (Spanish language version)

Madden NFL 09
2008

PS2, Xbox
Xbox 360, PS3, Wii

Nintendo DS, PSP

Brett Favre of the Green Bay Packers / Brett Favre of the New York Jets (alternative cover) / Roberto Garza of the Chicago Bears (Spanish language version)

Madden NFL 10
2009

PS2
Xbox 360, PS3, Wii

PSP, iOS

Troy Polamalu of the Pittsburgh Steelers and Larry Fitzgerald of the Arizona Cardinals

Madden NFL 11
2010

PS2
Xbox 360, PS3, Wii

PSP, iOS

Drew Brees of the New Orleans Saints

Madden NFL Football
2011

3DS

Madden NFL Football logo

Madden NFL 12
2011

PS2
Xbox 360, PS3, Wii

PSP, iOS, Android, BlackBerry Playbook

Peyton Hillis of the Cleveland Browns

Madden NFL 13
2012

Xbox 360, PS3, Wii
Wii U
PS Vita, iOS

Calvin Johnson of the Detroit Lions

Madden NFL 25
2013[22]

Xbox 360, PS3
Xbox One, PS4
iOS, Android

Barry Sanders of the Detroit Lions (Xbox 360 and PS3)
Adrian Peterson of the Minnesota Vikings (Xbox One and PS4)

Madden NFL 15
2014

Xbox 360, PS3
Xbox One, PS4

Richard Sherman of the Seattle Seahawks

Madden NFL Mobile
2014

iOS, Android

Richard Sherman of the Seattle Seahawks (2014 season), Odell Beckham Jr. of the New York Giants (2015 season), Rob Gronkowski of the New England Patriots/Von Miller of the Denver Broncos/Antonio Brown of the Pittsburgh Steelers (2016 season), Tom Brady of the New England Patriots (2017 season)

Madden NFL 16
2015

Xbox 360, PS3
Xbox One, PS4

Odell Beckham Jr. of the New York Giants

Madden NFL 17
2016

Xbox 360, PS3
Xbox One, PS4

Rob Gronkowski of the New England Patriots

Madden NFL 18
2017

Xbox One, PS4

Tom Brady of the New England Patriots

text: 1980s: Creation[edit]

text:
“
The real reason that I founded Electronic Arts was because I wanted to make computerized versions of games like Strat-O-Matic.
”

— Trip Hawkins[23]

text: Trip Hawkins created a clone of the Strat-o-Matic paper and dice-based football simulation game as a teenager. The game was unsuccessful due to its complexity, and he hoped to one day delegate its rules to a computer. At Harvard College, where Hawkins played football for the Crimson, he wrote a football simulation for the PDP-11 minicomputer which, he later said, predicted that the Miami Dolphins would defeat the Minnesota Vikings 23–6 (actually 24–7) in the 1974 Super Bowl.[4][24] After founding Electronic Arts in 1982[4]—"The real reason that I founded [it] was because I wanted to make computerized versions of games like Strat-O-Matic", Hawkins later said[23][9]—the company began designing a microcomputer football game. Hawkins first approached his favorite player Joe Montana to endorse the proposed game but the quarterback already had an endorsement deal with Atari Inc., and his second choice, Cal coach Joe Kapp, demanded royalties.[4]

text: In 1984 Hawkins approached Madden. He and game producer Joe Ybarra arranged a follow-up meeting with the broadcaster during an Amtrak train trip over two days because of Madden's fear of flying.[4][25][26][5] The EA executives promised that the proposed game would be a sophisticated football simulation, and asked the retired Oakland Raiders coach for his endorsement and expertise. Madden knew nothing about computers beyond his telestrator but agreed; he had taught a class at the University of California, Berkeley called "Football for Fans", and envisioned the program as a tool for teaching and testing plays.[4][15] (Madden continues to see the game as an educational tool. When asked in 2012 to describe Madden NFL, he called it "a way for people to learn the game and participate in the game at a pretty sophisticated level".[5]) Hawkins and Ybarra during the train trip learned football plays and strategies from Madden from sunrise to midnight.[4]

text: EA likely expected Madden to endorse the game without participating in its design. Early plans envisioned six or seven players per team because of technical limitations but Madden insisted on having 11 players,[4][5] stating "I'm not putting my name on it if it's not real."[26] Ybarra, who had played chess, not football, in high school, became an expert on the subject through his work, but found that 11 players overwhelmed contemporary home computers. Most projects that are as delayed as Madden are canceled; Ybarra and developer Robin Antonick needed three years, more than twice the length of the average development process. The project became known within the company as "Trip's Folly", and Madden believed at times that EA had given up.[4]

text: The company hired Bethesda Softworks to finish the game, but this only got them partway to their goal. While EA used many of its designs, including contributions to their physics engine,[27] within a year Bethesda stopped working on Madden and sued EA over EA's failure to publish new versions of Bethesda's Gridiron! football game. This added to the delay.[26] After a final development push, John Madden Football debuted in 1988 for the Apple II series of computers. Hawkins and an exhausted Ybarra ("All my memories are of pain") were able to move on to other projects.[4]

text: EA had a copy of the 1980 Raiders playbook, and hired San Francisco Chronicle writer Frank Cooney, who had designed his own figurine football game with numerical skill ratings. Although the company could not yet legally use NFL teams' or players' names, Cooney obtained real plays from NFL teams. The back of the box called the game "The First Real Football Simulation" and quoted Madden: "Hey, if there aren't 11 players, it isn't real football." Documentation included diagrams of dozens of offensive and defensive plays with Madden's commentary on coaching strategies and philosophy.[28] The game sold moderately well[4] but given the sophisticated playbook its interface was complex, and Madden's insistence on 11 players caused the game to run slowly.[26]

text: During this period, Madden turned down the opportunity to buy an "unlimited" number of options for EA stock in its initial public offering, a decision he later called "the dumbest thing I ever did in my life".[4][5]

text: In early 1990 EA hired Park Place Productions to develop Madden for the Sega Genesis video game console. Park Place had developed ABC Monday Night Football with "arcade-style, action-heavy" game play, and its Madden also emphasized hyperreality compared to the computer version's focus on exact simulation.[4][6] Impressed with Park Place's work, EA chose it for the Genesis Madden instead of completing an in-house version by Antonick.[29]

text: EA reverse engineered the console to sell the game without paying the standard $8 to $10 license fee per cartridge to Sega, then proposed a compromise of $2 per cartridge and a $2 million cap on the fee. The console maker agreed, afraid that EA would sell its reverse-engineered knowledge to other companies; the agreement saved EA $35 million over the next three years. As its own Joe Montana-endorsed football game would miss the 1990 Christmas shopping season, Sega asked EA to let it sell Madden with the Montana name. EA refused, but offered an inferior alternative that lacked Madden's 3D graphics and most of its 113 plays.[4][6] Joe Montana Football sold well despite shipping after Christmas 1990, and remained popular after BlueSky Software took over development.[26] John Madden Football for the Genesis, however, became both the first hugely successful Madden game—selling 400,000 copies when the company expected 75,000[29]—and the first killer app for EA and Sega, helping the console gain market share against the Super NES.[4][26] From 1992 to 1994, Mega placed the game at #1 in their monthly Top 100 Mega Drive Games of All Time.

text: In 1990, EA producer Richard Hilleman brought in veteran sports game designer Scott Orr, who had founded the mid-1980s Commodore 64 game publisher GameStar, and had led the design of their best-selling sports games. The team of Orr and Hilleman designed and led the development of what is today still recognizable as the modern Madden. Early versions of Madden were created by external development studios such as Bethesda, Visual Concepts, and Stormfront Studios. John Madden Football '92 also featured the ambulance which would run over any players in its path. After Visual Concepts failed to deliver Madden NFL '96 for the new PlayStation in 1995, EA hired Tiburon Entertainment for Madden NFL '97[26] and later acquired the company, centralizing development in-house.[4] It planned to release John Madden Football as its first sports-based arcade game, but the game was cancelled due to unenthusiastic reactions from play testers.[30] EA's refusal to release Madden and other sports titles for the Dreamcast in 1999 contributed to the console's lack of success and Sega's exit from the hardware market.[26]

text: Franchise Mode[edit]

text: This section needs expansion. You can help by adding to it. (September 2012)

text: In 1998 Electronic Arts added "Franchise Mode" to Madden, giving players the ability to play multiple seasons, make off-season draft picks, and trade players.[31] Within Franchise Mode, players take on the role of General Manager and manage all personnel matters, including contracts, free agency, draft picks, and hiring and firing coaches. The player also acts as a head coach-like character (although there is a head coach figure in-game), choosing which players to play, making substitutions, running practices, practicing gameplans, etc.

text: Players may play with any of the NFL's 32 franchises, and can choose whether or not to have trade deadlines, salary caps, and if they want to start their Franchise with a 49-round fantasy draft of all active NFL players. Players can also upload created teams for use in the game.

text: Once in game, players run training camp (individual drills for improving players' attributes), play in preseason games and compete in a regular 16-game NFL season, including playoffs and the Super Bowl. The player has the option to play any game in the simulation, including those involving other teams if they so desire, or may simulate through the games as they choose. Most versions of Madden give a player 30 years with their franchise, sometimes with an opportunity to apply for the Hall of Fame at the end of the simulation.

text: Madden NFL 2000[edit]

text: Madden NFL 2001[edit]

text: Madden NFL 2001 featured a segment called "Great Games" where one would be put in a situation where they control one team and would have to win the game with a set amount of time. If the player wins, they unlock either a new team or a stadium. Overall, there were more than 60 teams and over 80 stadiums in Madden NFL 2001.

text: Madden NFL 2002[edit]

text: Madden NFL 2002 featured for the first time Create-A-Team where one would make a team and play with that team in either Play Now or Franchise mode. It also featured Create-A-League mode but it never caught on. Create-A-Team was not featured in Madden NFL 13 and moving teams was first featured in Madden NFL 2004 called "Stadium" in the Franchise mode of the game. Madden NFL 2002 was the 2nd highest selling game in 2002.

text: Madden NFL 2003[edit]

text: There are multiple modes of game play, from a quick head-to-head game to running a team for a whole season or even multiple seasons. Online play, which was a new feature for Madden NFL 2003 (in this version there are also mini-camp challenges) was only available for users of the PlayStation 2 console, Xbox console, or a Microsoft Windows PC until early 2004.

text: Madden NFL 2004[edit]

text: Also, starting with Madden NFL 2004, EA Sports created the new Playmaker tool, using the right analog joystick found on each of the adjustments previously unavailable in prior installments of the franchise.[32] One such adjustment includes the ability to switch which direction a running play was going without changing the formation. Prior to the Playmaker tool, the Player could only call one of four available "hot routes." With Playmaker and the use of the right thumb stick, the player is given 4 additional Hot Route options. When the quarterback has the ball the Playmaker Tool can be used to make receivers alter their routes mid-play. When running the ball on offense, the runner can control the direction in which the blocker is going. Defensive alignment adjustments, however, were not available leading to obvious imbalance in favor of the Offensive player.

text: Madden NFL 2005[edit]

text: In Madden NFL 2005, EA Sports ran a campaign with the Theme "Fear the D" emphasising their improvements on the "other side of the ball." In an attempt to re-balance the players experience, EA gave a Playmaker Tool to the defense. Similar to the offensive Playmaker Tool, the defensive Playmaker allows the player to make pre-snap defensive adjustments. EA Sports further utilized the right analog joystick on defense by creating the "Hit Stick", an option on defense that allows the controlled player to make big hits, with a simple flick, that increases the chances the ball carrier will fumble. Also introduced for the first time is the "Formation Shift." This new feature allowed players to shift their formation in the pre-snap audible menu without actually changing the play. For example, if you call a run play up the middle out of a goal line formation, you could then call a formation shift and make your players spread out into a four wide receiver formation while still in the same running play. The problem with this new function was that EA also added a fatigue penalty for the defense causing defensive players to get more tired each time there was a formation shift. This led to players on offense calling multiple formation shifts each play making the defensive players too exhausted to keep up and force them to substitute out of the game until they are fully rested. This led to more imbalance that could only be fixed by turning off fatigue.

text: 2005 also added "EA Sports Radio", a fictional show that plays during the menu screen of Franchise mode to provide a greater sense of a storyline during gameplay. It features Tony Bruno as the host, who often interviews players and coaches about how the season is going and also has quiz questions in which fake listeners call in to make attempts at answering football-related questions. It included mock interviews of famous NFL players and coaches throughout the in-game season. Some fans have criticized EA Sports for not including new features to the 'programming' as the radio became stale after only two seasons in franchise mode, but the feature drew acclaim for adding content to the Franchise menu. Also added was the Newspaper where the player could look at National News from licensed USA Today and Licensed Local papers for almost each of the 32 NFL teams. Lastly, 2005 also saw the introduction of multiple progressions during franchise mode. Previously NFL players in Madden would only progress or regress at the end of each season. Now at the end of Week 5, 11, and 17 the game would use a program to "progress" players based on their performance in addition to end of season progression.

text: Madden NFL 06[edit]

text: In Madden NFL 06, the "Truck Stick" was introduced. This feature allows the offensive player to lower his shoulder and break a tackle, or back juke to avoid one. Another new feature is the Superstar Mode, which allows the player to take control of a rookie, and progress through his career.[33] This includes an IQ test, interviews, workouts, the NFL Draft, hiring an agent, and other aspects of a superstar's life.

text: EA also introduced the QB Vision feature in the 2006 installment. With this feature, a cone of spotlight emits from the quarterback during passing plays, simulating his field of vision. To make an accurate pass, the quarterback must have his intended receiver in his field of vision. Passing to a receiver not in the cone reduces pass accuracy significantly. The size of the quarterback's vision cone is directly correlated to his Awareness and Passer Accuracy rating; Brett Favre and Peyton Manning see nearly the entire field at once, whereas an inexperienced quarterback such as J. P. Losman or Kyle Boller sees only a sliver of the field.[4] This feature also allows for bigger plays and more interceptions.

text: Also, EA sports added the Smart Route. This means that when pressing a hot route to the corresponding receiver, you put the analog stick down and the receiver will run to the first down, and you can throw him the ball.

text: While current gen Madden remained the same with the exception of a "Smart Route" and "QB Vision", this was also the first year Madden was released on the next-gen Xbox 360. It was completely stripped down, almost every change made in the previous gen was wiped away.

text: Madden NFL 07[edit]

text: In Madden NFL 07, EA introduced Lead Blocker Controls which allow users to control blockers during running plays. In addition, EA redefined the Truck Stick into the Highlight Stick. With the Highlight Stick, users can have their running backs perform different running moves and combos, instead of just bowling over defenders. Truck Stick features still exist for bigger backs, but not for smaller backs who would never realistically use them anyway. Instead, more agile backs perform acrobatic ducks and dodges to avoid tackles.[34]

text: Madden NFL 08[edit]

text: In Madden NFL 08, the Weapons feature was added, allowing superstar players to be noticed. Randy Moss, for example, is a Go-To-Guy, allowing him to make amazing one-handed grabs. Peyton Manning is a Franchise QB. It also includes new skill drills, Hit Stick 2.0, and Ring of a Champion features. Tennessee Titans quarterback Vince Young is on the cover. Madden NFL 08 was also the last GameCube game ever released. 2008 marked the last year of the PC version of the game.

text: Madden NFL 09[edit]

text: Madden NFL 09 was released on August 12, 2008. Citing business concerns, EA chose not to release it on the PC platform.[35] The game features quarterback Brett Favre on the front cover.[36] Madden NFL 09 was the first of the series to offer online, league game play, allowing up to 32 players to compete in an online, simulated NFL season. EA Sports Senior Producer Phil Frazier, up to 32 players were able to participate in competitive games, the NFL Draft and conduct trades between their teams. The game was also the first of the series to incorporate a Madden IQ. The Madden IQ is used to automatically gauge your skills through a series of mini-games consisting of run offense, pass offense, run defense, and pass defense. At the end of each of the drills, the player receives a score ranging from rookie to all-Madden. The final Madden IQ is a mixture of those scores which is used to control the game's difficulty.[4][37][38]

text: Madden NFL 10[edit]

text: Madden NFL 10 was released on August 14, 2009.[39] Compared to previous iterations, Madden NFL 10 has been extremely transparent with its development efforts, maintaining a weekly blog updates as well as a constant presence on various message boards. A new design team has also taken over the game, including members from NFL Head Coach 09. The direction of Madden NFL 10 has been shifted to much more of a realistic and simulation focus, with info already released including Procedural Awareness (a robust head tracking system), a new philosophy on player ratings, and big improvements to realism in QB play, WR/DB play, and other areas across the game. Madden 10 has several new features including the PRO-TAK animation technology, which allows up to nine man gang tackles and fumble pile-ups to help players 'fight for every yard', in this year's tagline. Madden 10 also features an in-game weekly recap show called The Extra Point. Madden 10 offers a series of multiple play packages. This allows for more options to score. This version features a completely overhauled rating system for players, featuring new categories such as throw on the run and specific ratings for short, medium, and deep passes.[40] The game's soundtrack features rap, alternative rock, rap metal and hard rock bands such as Nirvana, Pantera, System of a Down, and Kid Rock.

text: Madden NFL 11[edit]

text: Madden NFL 11 was released on July 27, 2010 (moved up from its original release date of August 10, 2010 for promotional reasons[41]), and features Drew Brees on the cover. It features several new additions to the franchise, such as Online Team Play,[42] Online Scouting[43] and online attribute boosts for co-op play.[44] Along with these new game additions is a new rating (sponsored by Old Spice) known as Swagger.[45] Although early speculation was that this new rating would be reflective of "confidence" or "composure," it was quickly confirmed to be directly tied to a player's personality for celebrations.[46]

text: Madden NFL 12[edit]

text: Madden NFL 12 was released on August 25, 2011. The release was delayed by two weeks due to the NFL lockout,[47] and features Cleveland Browns running back Peyton Hillis on the cover. However, there is a limited edition in which the cover features St. Louis Rams running back Marshall Faulk.

text: Madden NFL 13[edit]

text: Madden NFL 13 was released on August 28, 2012, and features Detroit Lions wide receiver Calvin Johnson as the cover athlete. Madden NFL 13 is the first Madden game to be released on the PlayStation Vita, and is also the first game in the series to have Kinect support as well as a new physics engine promoting real in game physics.[48]

text: Madden NFL 13 included a complete revamp to online franchise mode which became known as Connected Careers Mode (CCM). Some of the new CCM features included player contracts, the ability to trade draft picks, a salary cap, and up to 30 seasons worth of gameplay.[49]

text: Madden NFL 25[edit]

text: In early 2013, EA Sports announced that the next installment of the Madden series was released on August 27, 2013. As this installment is the 25th anniversary of the series,[50] the game is called Madden NFL 25, instead of Madden NFL 14 with the year like the previous versions.[51] The cover vote consisted of two brackets containing past players ("Old School") and active players ("New School").[52]

text: "Old School" player and Pro Football Hall of Famer Barry Sanders was chosen as the cover athlete for Madden NFL 25 on the April 24, 2013, episode of ESPN's SportsNation. The "New School" finalist was Adrian Peterson.[53]

text: Madden NFL 15[edit]

text: On March 13, 2014 EA Sports posted on its website that user would be able to design and submit uniforms for Connected Careers by March 17, 2014 for "the next Madden NFL."[54] On April 28, 2014, EA announced the release of Madden 15 pre-ordering in a release video with NFL linebacker and 2013 Defensive Player of the Year Luke Kuechly. The game was released August 26 in North America and on August 29 in the EU for Xbox One, PlayStation 4, Xbox 360 and the PlayStation 3. The game featured "dramatic all-new camera angles, as well as dynamic pre-game and halftime features."[55] During the Detroit Lions 10th pick of the 2014 NFL Draft, Barry Sanders announced fans again would be able to vote for the cover athlete.[56] On June 6, Seattle Seahawks cornerback Richard Sherman was announced as the cover athlete.[57]

text: Madden NFL 16[edit]

text: EA decided not to have players vote for the cover athlete through a traditional bracket, but rather through collectible cards in Madden NFL Mobile, or through Ultimate Team on the console devices. On May 4, 2015, the four finalists were announced for the 2016 game cover: New England Patriots tight end Rob Gronkowski, Arizona Cardinals cornerback Patrick Peterson, New York Giants wide receiver Odell Beckham Jr. and Pittsburgh Steelers wide receiver Antonio Brown. On May 13, Beckham Jr. beat out Gronkowski in a fan vote for the cover of Madden 16. It was released on August 25, 2015.[58]

text: Madden NFL 17[edit]

text: Madden NFL 17 was released on August 23, 2016. The features in the game include an upgrade of the Ground Game, a redesigned and better Franchise Mode, "Madden 365", new Ball Carrier UI Prompts, the new Path Assist and more.[59] New England Patriots tight end Rob Gronkowski serves as the cover athlete.[60]

text: Madden NFL 18[edit]

text: Madden NFL 18 was released on August 25, 2017.[61] The game is the first in the series to be developed in the Frostbite Engine, and incorporates a Story Mode, akin to The Journey in FIFA 17.[62] It was announced that Tom Brady would be on the cover, marking the second consecutive year where a Patriot will be on the cover.[63] Furthermore, an enhanced G.O.A.T edition was also announced.[64]

text: License history and spinoffs[edit]

text: Licensing[edit]

text: Until 1993, the Madden series did not have official licenses from the National Football League or National Football League Players Association (NFLPA). Madden NFL '94 was the first game in the series to include real NFL teams, and Madden NFL '95 added an NFLPA license for real players through the National Football League Players Incorporated (NFLPI).[65] The licenses restrict EA from including certain content in current Madden games, such as the humorous ambulance that picks up injured players in 1991's John Madden Football II.[4] The NFL Coaches Association sold the rights to have NFL coaches' names appear in the Madden NFL games; Madden NFL 2001 was the first game in the series to feature this license.[66] Neither New England Patriots coach Bill Belichick nor Bill Parcells appeared in the game as they are not members of the NFL Coaches Association. Likewise, non-NFLPA players (such as Thurman Thomas during his playing career) do not appear in the game, instead being replaced with generic placeholders.

text: Exclusivity[edit]

text: In 2004, EA signed an exclusive license through 2009 with the NFL and the NFLPI to give the company the exclusive rights to use the NFL's teams, stadia, and players in a video game.[67] This exclusive license prevents other official NFL video games. The deal, reportedly worth $300 million and later extended to 2013,[4] has been widely criticized. Some competitors, such as the Blitz: The League series, have elected to continue, seeking to distinguish themselves through innovative gameplay while others, such as the NFL 2K series, have ceased production. In 2007, 2K Sports released All Pro Football 2K8, which used former NFL stars.

text: Head Coach series[edit]

text: In August 2006, EA Sports debuted NFL Head Coach, which utilized the Madden engine to create a football management simulation. The game was criticized as buggy and unrealistic. EA Tiburon rebuilt the game from the ground up, addressing flaws and creating a proprietary engine, over the course of three years. NFL Head Coach 09 was released on August 12, 2008 bundled with the special edition of Madden NFL 09 and as a standalone game on September 2, 2008.

text: Madden Arcade[edit]

text: Released on November 24, 2009,[68] the game is 5-on-5 and takes the best 10 players from each of the 32 NFL teams.[69]

text: Madden NFL Football[edit]

text: Madden NFL Football was released as the launch title for the Nintendo 3DS on March 27, 2011.[70]

text: Reception[edit]

text: In 1996, Next Generation listed the Genesis installments of the series collectively as number 30 on their "Top 100 Games of All Time", calling them "One of the best two-player games of all time, the game that reinvented EA, and (along with Sonic the Hedgehog) the game that launched Sega's 16-bit assault on Nintendo."[71]

text: Madden Curse[edit]

text: Prior to 1999, every annual installment of the Madden NFL series primarily featured Madden on its cover.[4][72] In 1999, Electronic Arts selected Garrison Hearst to appear on the PAL version's cover, and has since featured one of the league’s top players on every annual installment[73] despite Madden's opposition.[4] While appearing on the cover has become an honor akin to appearing on the Wheaties box,[4] much like the Sports Illustrated Cover Jinx, certain players who appeared on Madden video game box art have experienced a decline in performance, usually due to an injury. This apparent run of misfortune for Madden cover athletes has been dubbed the "Madden Curse."[74]

text: When asked about the Madden Curse, EA Sports' Chris Erb said, "I don't know that we believe in the curse. The players don't believe in the curse."[75] Running back Shaun Alexander, who was featured on the cover of Madden NFL 07, commented "Do you want to be hurt and on the cover, or just hurt?" Madden NFL 08 cover athlete Vince Young expressed skepticism,[76][77] while Madden NFL 12 cover athlete Peyton Hillis attributed his subpar season that year to the curse.[78]

text: The perception that the curse is real has resulted in some fans lobbying for their favorite players not to be on the cover, such as fans of LaDainian Tomlinson who were strongly opposed to EA Sports' initial decision to feature him on the cover of Madden NFL 08, so much that a fan created SaveLTfromMadden.com to voice their disdain.[79][80][81] Tomlinson eventually declined the offer, but stated it was solely due to contract negotiations.[81] Starting with Madden NFL 11 EA has allowed fans to choose their favorite player for the cover.[82] However, EA believes that many fans vote against their favorite player to avoid the purported "curse".[5] It has become so prominent that bookmakers create odds on how likely an injury will occur to the player appearing on the cover.[83]

text: The injuries that Madden cover athletes experience can be attributed to the physical nature of football.[75] Also to earn the honor of being put on the game cover, a player is usually coming off of a strong year and some regression the following year is likely. Attributing some cause, such as a curse, to this randomness is a regression fallacy and a spurious correlation.

text: In December 2010, EA announced plans on developing a movie based on the Curse, which would be a comedy, and not based on fate-based horror movies like Final Destination.[84] However, EA Entertainment executive Pat O'Brien stated in October 2014 that EA is not working on a Madden Curse movie.[85]

text: Madden Bowl[edit]

text: The Madden Bowl is a single elimination tournament held on the most current edition of Madden NFL. It has been held since 1995 during Super Bowl weekend in the host city and, in the past, participation included NFL players and celebrities. The Madden Bowl's participation has changed over the years from being an event held with athletes, musicians, and celebrities, to become an event where only NFL players who are invited to participate get a chance to play. Participants in the Madden Bowl are free to choose whichever team they like. Winners receive a Madden Bowl trophy and recognition in the upcoming Madden video game.

text: The 2006 Madden Bowl, held during the weekend of Super Bowl XL in Detroit, Michigan, was televised on ESPN and premiered in April 2006. It is not to be confused with Madden Nation, which was a reality television show that chronicled a cross-country trip to crown the best Madden player in America, which also aired on ESPN.

text: From 2011 to 2012, the Madden Bowl competition utilizes the new Online Team Play feature included in Madden NFL 11. Rather than competing as individuals, players form groups of three to square-off for the trophy. After this feature was discontinued, the Madden Bowl competition continued in a Head-to-Head format.

text: Madden Bowl winners[edit]

text:
1995: Reggie Brooks
1996: Reggie Brooks
1997: Jimmy Spencer
1998: Morris Chestnut
1999: Ray Mickens
2000: Terry Jackson
2001: Jacquez Green
2002: Jacquez Green
2003: Dwight Freeney
2004: Dwight Freeney
2005: Michael Lewis
2006: Alex Smith
2007: Alex Smith
2008: Willis McGahee
2009: Antonio Bryant
2010: Maurice Jones-Drew
2011: Patrick Willis, Chad Ochocinco, and Maria Menounos
2012: Drew Brees, Jimmy Graham, and Tim Tebow
2013: LeSean McCoy
2014: Richard Sherman
2015: Patrick Peterson
2016: Eric Berry

tag: ul

text: Rookie Madden Bowl winners[edit]

text:
2006: Alex Smith
2007: Vince Young
2008: Devin Thomas
2009: Vernon Gholston

text: Annual EA Super Bowl simulation[edit]

text: Since 2004, EA Sports has run a simulation of the Super Bowl using the latest game in the Madden NFL series and announced the result. The game simulations conducted by EA have correctly predicted ten of the last 14 Super Bowl winners. The company accurately predicted the final score for the 2015 game and other details, including a score of 24–14 in favor of Seattle in the third quarter, despite skepticism within EA that Seattle would lose after a double-digit lead.[86][2] The predictions were incorrect in 2008, 2011, 2014, and in 2016. EA also releases a computer-generated description of the simulated game as if it were a summary of the real Super Bowl. The results of the simulated and actual Super Bowl games are listed below.

text:
Year
Super
Bowl
Madden's winner
Madden's loser
Actual
score
Madden's prediction
Madden's
record
Sources

Score
Result
Points diff.

2004
XXXVIII
New England Patriots
Carolina Panthers
32 – 29
23 – 20
Y
Y
1–0
[87]

2005
XXXIX
New England Patriots
Philadelphia Eagles
24 – 21
47 – 31
Y
N
2–0
[88]

2006
XL
Pittsburgh Steelers
Seattle Seahawks
21 – 10
24 – 19
Y
N
3–0
[89]

2007
XLI
Indianapolis Colts
Chicago Bears
29 – 17
38 – 27
Y
N
4–0
[90]

2008
XLII
New England Patriots
New York Giants
17 – 14
30 – 38
N
N
4–1
[91]

2009
XLIII
Pittsburgh Steelers
Arizona Cardinals
27 – 23
28 – 24
Y
Y
5–1
[92]

2010
XLIV
New Orleans Saints
Indianapolis Colts
31 – 17
35 – 31
Y
N
6–1
[93]

2011
XLV
Pittsburgh Steelers
Green Bay Packers
31 – 25
20 – 24
N
N
6–2
[94]

2012
XLVI
New York Giants
New England Patriots
21 – 17
27 – 24
Y
N
7–2
[95]

2013
XLVII
Baltimore Ravens
San Francisco 49ers
34 – 31
27 – 24
Y
Y
8–2
[96]

2014
XLVIII
Denver Broncos
Seattle Seahawks
43 – 8
28 – 31
N
N
8–3
[97]

2015
XLIX
New England Patriots
Seattle Seahawks
28 – 24
28 – 24
Y
Y
9–3
[98]

2016
50
Carolina Panthers
Denver Broncos
24 – 10
20 – 24
N
N
9–4
[99]

2017
LI
New England Patriots
Atlanta Falcons
34 – 28
27 – 24
Y
N
10–4
[100]


document_title: T cell

question_text: where does positive selection of t cells occur

text: T cell

text: Types[edit]

text: Effector[edit]

text: Effector cells are the superset of all the various T cell types that actively respond immediately to a stimulus, such as co-stimulation. This includes helper, killer, regulatory, and potentially other T cell types. Memory cells are their opposite counterpart that are longer lived to target future infections as necessary.

text: Helper[edit]

text: T helper cells (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages.  These cells are also known as CD4+ T cells because they express the CD4 glycoprotein on their surfaces.  Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, which are expressed on the surface of antigen-presenting cells (APCs).  Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response.  These cells can differentiate into one of several subtypes, including TH1, TH2, TH3, TH17, TH9, or TFH, which secrete different cytokines to facilitate different types of immune responses.  Signalling from the APC directs T cells into particular subtypes.[4]

text: Cytotoxic (Killer)[edit]

text: Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also implicated in transplant rejection.  These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surfaces.  These cells recognize their targets by binding to antigen associated with MHC class I molecules, which are present on the surface of all nucleated cells.  Through IL-10, adenosine, and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state, which prevents autoimmune diseases.

text: Memory[edit]

text: Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen within the context of an MHC molecule on the surface of a professional antigen presenting cell (e.g. a dendritic cell). Appropriate co-stimulation must be present at the time of antigen encounter for this process to occur.  Historically, memory T cells were thought to belong to either the effector or central memory subtypes, each with their own distinguishing set of cell surface markers (see below).[5] Subsequently, numerous new populations of memory T cells were discovered including tissue-resident memory T (Trm) cells, stem memory TSCM cells, and virtual memory T cells.  The single unifying theme for all memory T cell subtypes is that they are long-lived and can quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen. By this mechanism they provide the immune system with "memory" against previously encountered pathogens. Memory T cells may be either CD4+ or CD8+ and usually express CD45RO.[6]

text: Memory T cell subtypes:

text:
Central memory T cells (TCM cells) express CD45RO, C-C chemokine receptor type 7 (CCR7), and L-selectin (CD62L). Central memory T cells also have intermediate to high expression of CD44. This memory subpopulation is commonly found in the lymph nodes and in the peripheral circulation. (Note- CD44 expression is usually used to distinguish murine naive from memory T cells).
Effector memory T cells (TEM cells and TEMRA cells) express CD45RO but lack expression of CCR7 and L-selectin.  They also have intermediate to high expression of CD44. These memory T cells lack lymph node-homing receptors and are thus found in the peripheral circulation and tissues.[7] TEMRA stands for terminally differentiated effector memory cells re-expressing CD45RA, which is a marker usually found on naive T cells.[8]
Tissue resident memory T cells (TRM) occupy tissues (skin, lung, etc..) without recirculating. One cell surface marker that has been associated with TRM is the integrin αeβ7.[9]
Virtual memory T cells differ from the other memory subsets in that they do not originate following a strong clonal expansion event.  Thus, although this population as a whole is abundant within the peripheral circulation, individual virtual memory T cell clones reside at relatively low frequencies. One theory is that homeostatic proliferation gives rise to this T cell population. Although CD8 virtual memory T cells were the first to be described,[10] it is now known that CD4 virtual memory cells also exist.[11]

text: Regulatory (suppressor)[edit]

text:
Regulatory T cells (suppressor T cells) are crucial for the maintenance of immunological tolerance.  Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress autoreactive T cells that escaped the process of negative selection in the thymus.
Suppressor T cells along with Helper T cells can collectively be called Regulatory T cells due to their regulatory functions.[12]

text: Two major classes of CD4+ Treg cells have been described — FOXP3+ Treg cells and FOXP3− Treg cells.

text: Regulatory T cells can develop either during normal development in the thymus, and are then known as thymic Treg cells, or can be induced peripherally and are called peripherally derived Treg cells.  These two subsets were previously called "naturally occurring", and "adaptive" or "induced", respectively.[13]  Both subsets require the expression of the transcription factor FOXP3 which can be used to identify the cells. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX.

text: Several other types of T cell have suppressive activity, but do not express FOXP3. These include Tr1 cells and Th3 cells, which are thought to originate during an immune response and act by producing suppressive molecules. Tr1 cells are associated with IL-10, and Th3 cells are associated with TGF-beta. Recently, Treg17 cells have been added to this list.[14]

text: Natural killer T cell[edit]

text: Natural killer T cells (NKT cells – not to be confused with natural killer cells of the innate immune system) bridge the adaptive immune system with the innate immune system.  Unlike conventional T cells that recognize peptide antigens presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d.  Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e., cytokine production and release of cytolytic/cell killing molecules).  They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses.[15]

text: Mucosal associated invariant[edit]

text: MAIT cells display innate, effector-like qualities.[16][17] In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection.[16] The MHC class I-like protein, MR1, is responsible for presenting bacterially-produced vitamin B metabolites to MAIT cells.[18][19][20] After the presentation of foreign antigen by MR1, MAIT cells secretes pro-inflammatory cytokines and are capable of lysing bacterially-infected cells.[16][20] MAIT cells can also be activated through MR1-independent signaling.[20] In addition to possessing innate-like functions, this T cell subset supports the adaptive immune response and has a memory-like phenotype.[16] Furthermore, MAIT cells are thought to play a role in autoimmune diseases, such as multiple sclerosis, arthritis and inflammatory bowel disease,[21][22] although definitive evidence is yet to be published.[23][24][25][26]

text: Gamma delta T cells[edit]

text: Gamma delta T cells (γδ T cells) represent a small subset of T cells that possess a distinct T cell receptor (TCR) on their surfaces.  A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR chains.  However, in γδ T cells, the TCR is made up of one γ-chain and one δ-chain.  This group of T cells is much less common in humans and mice (about 2% of total T cells); and are found mostly in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes.  In rabbits, sheep, and chickens, the number of γδ T cells can be as high as 60% of total T cells.  The antigenic molecules that activate γδ T cells are still widely unknown.  However, γδ T cells are not MHC-restricted and seem to be able to recognize whole proteins rather than requiring peptides to be presented by MHC molecules on APCs.  Some murine γδ T cells recognize MHC class IB molecules, though.  Human Vγ9/Vδ2 T cells, which constitute the major γδ  T cell population in peripheral blood, are unique in that they specifically and rapidly respond to a set of nonpeptidic phosphorylated isoprenoid precursors, collectively named phosphoantigens, which are produced by virtually all living cells.  The most common phosphoantigens from animal and human cells (including cancer cells) are isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMPP).  Many microbes produce the highly active compound hydroxy-DMAPP (HMB-PP) and corresponding mononucleotide conjugates, in addition to IPP and DMAPP.  Plant cells produce both types of phosphoantigens.  Drugs activating human Vγ9/Vδ2 T cells comprise synthetic phosphoantigens and aminobisphosphonates, which upregulate endogenous IPP/DMAPP.

text: Development[edit]

text: All T cells originate from haematopoietic stem cells in the bone marrow.  Haematopoietic progenitors (lymphoid progenitor cells) from haematopoietic stem cells populate the thymus and expand by cell division to generate a large population of immature thymocytes.[27]  The earliest thymocytes express neither CD4 nor CD8, and are therefore classed as double-negative (CD4−CD8−) cells.  As they progress through their development, they become double-positive thymocytes (CD4+CD8+), and finally mature to single-positive (CD4+CD8− or CD4−CD8+) thymocytes that are then released from the thymus to peripheral tissues. There is some evidence of double-positive T-cells in the periphery, though their prevalence and function is uncertain.[28][29] In laboratory, T-cells can be converted into functional neurons within three weeks. [30]

text: About 98% of thymocytes die during the development processes in the thymus by failing either positive selection or negative selection, whereas the other 2% survive and leave the thymus to become mature immunocompetent T cells. Increasing evidence indicates microRNAs, which are small noncoding regulatory RNAs, could impact the clonal selection process during thymic development. For example, miR-181a was found to play a role in the positive selection of T lymphocytes.[31]

text: The thymus contributes fewer cells as a person ages.  As the thymus shrinks by about 3%[32] a year throughout middle age, a corresponding fall in the thymic production of naïve T cells occurs, leaving peripheral T cell expansion to play a greater role in protecting older subjects.

text: Beta selection[edit]

text: Common lymphoid precursor cells that migrate to the thymus become known as T-cell precursors (or thymocytes) and do not express a T cell receptor. Broadly speaking, the double negative (DN) stage is focused on producing a functional β-chain whereas the double positive (DP) stage is focused on producing a functional α-chain, ultimately producing a functional αβ T cell receptor. As the developing thymocyte progresses through the four DN stages (DN1, DN2, DN3, and DN4), the T cell expresses an invariant α-chain but rearranges the β-chain locus. If the rearranged β-chain successfully pairs with the invariant α-chain, signals are produced which cease rearrangement of the β-chain (and silence the alternate allele) and result in proliferation of the cell.[33] Although these signals require this pre-TCR at the cell surface, they are independent of ligand binding to the pre-TCR. These thymocytes will then express both CD4 and CD8 and progresses to the double positive (DP) stage where selection of the α-chain takes place. If a rearranged β-chain does not lead to any signalling (e.g. as a result of an inability to pair with the invariant α-chain), the cell may die by neglect (lack of signalling).

text: Positive selection[edit]

text: Positive selection "selects for" T cells capable of interacting with MHC. Positive selection involves the production of a signal by double-positive precursors that express either MHC Class I or II restricted receptors. The signal produced by these thymocytes result in RAG gene repression, long-term survival and migration into the medulla, as well as differentiation into mature T cells. The process of positive selection takes a number of days.[34]

text: Double-positive thymocytes (CD4+/CD8+) move deep into the thymic cortex, where they are presented with self-antigens.  These self-antigens are expressed by thymic cortical epithelial cells on MHC molecules on the surface of cortical epithelial cells.  Only those thymocytes that interact with MHC-I or MHC-II appropriately (i.e., not too strongly or too weakly) will receive a vital "survival signal". All that cannot (i.e., if they do not interact strongly enough, or if they bind too strongly) will die by "death by neglect" (no survival signal).  This process ensures that the selected T-cells will have an MHC affinity that can serve useful functions in the body (i.e., the cells must be able to interact with MHC and peptide complexes to effect immune responses).  The vast majority of all thymocytes will die during this process.

text: A thymocyte's fate is determined during positive selection.  Double-positive cells (CD4+/CD8+) that interact well with MHC class II molecules will eventually become CD4+ cells, whereas thymocytes that interact well with MHC class I molecules mature into CD8+ cells.  A T cell becomes a CD4+ cell by down-regulating expression of its CD8 cell surface receptors.  If the cell does not lose its signal, it will continue downregulating CD8 and become a CD4+, single positive cell.[35]  But, if there is a signal interruption, the cell stops downregulating CD8 and switches over to downregulating CD4 molecules, instead, eventually becoming a CD8+, single positive cell.

text: This process does not remove thymocytes that may cause autoimmunity.  The potentially autoimmune cells are removed by the process of negative selection, which occurs in the thymic medulla (discussed below).

text: Negative selection[edit]

text: Negative selection removes thymocytes that are capable of strongly binding with "self" MHC peptides.  Thymocytes that survive positive selection migrate towards the boundary of the cortex and medulla in the thymus.  While in the medulla, they are again presented with a self-antigen presented on the MHC complex of medullary thymic epithelial cells (mTECs).[36]  mTECs must be AIRE+ to properly express self-antigens from all tissues of the body on their MHC class I peptides.  Some mTECs are phagocytosed by thymic dendritic cells; this allows for presentation of self-antigens on MHC class II molecules (positively selected CD4+ cells must interact with MHC class II molecules, thus APCs, which possess MHC class II, must be present for CD4+ T-cell negative selection).  Thymocytes that interact too strongly with the self-antigen receive an apoptotic signal that leads to cell death.  However, some of these cells are selected to become Treg cells.  The remaining cells exit the thymus as immature naïve T cells (also known as recent thymic emigrants [37]).  This process is an important component of central tolerance and serves to prevent the formation of self-reactive T cells that are capable of inducing autoimmune diseases in the host.

text: In summary, β-selection is the first checkpoint, where the T cells that are able to form a functional pre-TCR with an invariant alpha chain and a functional beta chain are allowed to continue development in the thymus.  Next, positive selection checks that T cells have successfully rearranged their TCRα locus and are capable of recognizing peptide-MHC complexes with appropriate affinity.  Negative selection in the medulla then obliterates T cells that bind too strongly to self-antigens expressed on MHC molecules.  These selection processes allow for tolerance of self by the immune system.  Typical T cells that leave the thymus (via the corticomedullarly junction) are self-restricted, self-tolerant, and singly positive.

text: Activation[edit]

text: Activation of CD4+ T cells occurs through the simultaneous engagement of  the T-cell receptor and a co-stimulatory molecule (like CD28, or ICOS) on the T cell by the major histocompatibility complex (MHCII) peptide and co-stimulatory molecules  on the APC.  Both are required for production of an effective immune response; in the absence of  co-stimulation, T cell receptor signalling alone results in anergy.  The signalling pathways downstream from co-stimulatory molecules usually engages the PI3K pathway generating PIP3 at the plasma membrane and recruiting PH domain containing signaling molecules like PDK1 that are essential for the activation of PKCθ, and eventual IL-2 production. Optimal CD8+ T cell response relies on CD4+ signalling.[39] CD4+ cells are useful in the initial antigenic activation of naïve CD8 T cells, and sustaining memory CD8+ T cells in the aftermath of an acute infection. Therefore, activation of CD4+ T cells can be beneficial to the action of CD8+ T cells.[40][41][42]

text: The first signal is provided by binding of the T cell receptor to its cognate peptide presented on MHCII on an APC.  MHCII is restricted to so-called professional antigen-presenting cells, like dendritic cells, B cells, and macrophages, to name a few.  The peptides presented to CD8+ T cells by MHC class I molecules are 8–13 amino acids in length; the peptides presented to CD4+ cells by MHC class II molecules are longer, usually 12–25 amino acids in length,[43] as the ends of the binding cleft of the MHC class II molecule are open.

text: The second signal comes from co-stimulation, in which surface receptors on the APC are induced by a relatively small number of stimuli, usually products of pathogens, but sometimes breakdown products of cells, such as necrotic-bodies or heat shock proteins.  The only co-stimulatory receptor expressed constitutively by naïve T cells is CD28, so co-stimulation for these cells comes from the CD80 and CD86 proteins, which together constitute the B7 protein, (B7.1 and B7.2, respectively) on the APC.  Other receptors are expressed upon activation of the T cell, such as OX40 and ICOS, but these largely depend upon CD28 for their expression.  The second signal licenses the T cell to respond to an antigen.  Without it, the T cell becomes anergic, and it becomes more difficult for it to activate in future.  This mechanism prevents inappropriate responses to self, as self-peptides will not usually be presented with suitable co-stimulation. Once a T cell has been appropriately activated (i.e. has received signal one and signal two) it alters its cell surface expression of a variety of proteins.  Markers of T cell activation include CD69, CD71 and CD25 (also a marker for Treg cells), and HLA-DR (a marker of human T cell activation). CTLA-4 expression is also up-regulated on activated T cells, which in turn outcompetes CD28 for binding to the B7 proteins. This is a checkpoint mechanism to prevent over activation of the T cell. Activated T cells also change their cell surface glycosylation profile.[44]

text: The T cell receptor exists as a complex of several proteins.  The actual T cell receptor is composed of two separate peptide chains, which are produced from the independent T cell receptor alpha and beta (TCRα and TCRβ) genes.  The other proteins in the complex are the CD3 proteins: CD3εγ and CD3εδ heterodimers and, most important, a CD3ζ homodimer, which has a total of six ITAM motifs.  The ITAM motifs on the CD3ζ can be phosphorylated by Lck and in turn recruit ZAP-70.  Lck and/or ZAP-70 can also phosphorylate the tyrosines on many other molecules, not least CD28, LAT and SLP-76, which allows the aggregation of signalling complexes around these proteins.

text: Phosphorylated LAT recruits SLP-76 to the membrane, where it can then bring in PLC-γ, VAV1, Itk and potentially PI3K.  PLC-γ cleaves PI(4,5)P2 on the inner leaflet of the membrane to create the active intermediaries diacylglycerol (DAG), inositol-1,4,5-trisphosphate (IP3); PI3K also acts on PIP2, phosphorylating it to produce phosphatidlyinositol-3,4,5-trisphosphate (PIP3).  DAG binds and activates some PKCs.  Most important in T cells is PKCθ, critical for activating the transcription factors NF-κB and AP-1.  IP3 is released from the membrane by PLC-γ and diffuses rapidly to activate calcium channel receptors on the ER, which induces the release of calcium into the cytosol.  Low calcium in the endoplasmic reticulum causes STIM1 clustering on the ER membrane and leads to activation of cell membrane CRAC channels that allows additional calcium to flow into the cytosol from the extracellular space.  This aggregated cytosolic calcium binds calmodulin, which can then activate calcineurin.  Calcineurin, in turn, activates NFAT, which then translocates to the nucleus.  NFAT is a transcription factor that activates the transcription of a pleiotropic set of genes, most notable, IL-2, a cytokine that promotes long-term proliferation of activated T cells.

text: PLCγ can also initiate the NF-κB pathway.  DAG activates PKCθ, which then phosphorylates CARMA1, causing it to unfold and function as a scaffold.  The cytosolic domains bind an adapter BCL10 via CARD (Caspase activation and recruitment domains) domains; that then binds TRAF6, which is ubiquitinated at K63.:513–523[45]  This form of ubiquitination does not lead to degradation of target proteins.  Rather, it serves to recruit NEMO, IKKα and -β, and TAB1-2/ TAK1.[46]  TAK 1 phosphorylates IKK-β, which then phosphorylates IκB allowing for K48 ubiquitination: leads to proteasomal degradation.  Rel A and p50 can then enter the nucleus and bind the NF-κB response element.  This coupled with NFAT signaling allows for complete activation of the IL-2 gene.[45]

text: While in most cases activation is dependent on TCR recognition of antigen, alternative pathways for activation have been described.  For example, cytotoxic T cells have been shown to become activated when targeted by other CD8 T cells leading to tolerization of the latter.[47]

text: In spring 2014, the T-Cell Activation in Space (TCAS) experiment was launched to the International Space Station on the SpaceX CRS-3 mission to study  how "deficiencies in the human immune system are affected by a microgravity environment".[48]

text: T cell activation is modulated by reactive oxygen species.[49]

text: Antigen discrimination[edit]

text: A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. infected or cancerous) cells in the body.[50] Healthy cells typically express a large number of self derived pMHC on their cell surface and although the T cell antigen receptor can interact with at least a subset of these self pMHC, the T cell generally ignores these healthy cells. However, when these very same cells contain even minute quantities of pathogen derived pMHC, T cells are able to become activated and initiate immune responses. The ability of T cells to ignore healthy cells but respond when these same cells contain pathogen (or cancer) derived pMHC is known as antigen discrimination. The molecular mechanisms that underlie this process are controversial.[50][51]

text: Clinical significance[edit]

text: Deficiency[edit]

text: Causes of T cell deficiency include lymphocytopenia of T cells and/or defects on function of individual T cells.  Complete insufficiency of T cell function can result from hereditary conditions such as severe combined immunodeficiency (SCID), Omenn syndrome, and cartilage–hair hypoplasia.[52]  Causes of partial insufficiencies of T cell function include acquired immune deficiency syndrome (AIDS), and hereditary conditions such as DiGeorge syndrome (DGS), chromosomal breakage syndromes (CBSs), and B-cell and T-cell combined disorders such as ataxia-telangiectasia (AT) and Wiskott–Aldrich syndrome (WAS).[52]

text: The main pathogens of concern in T cell deficiencies are intracellular pathogens, including Herpes simplex virus, Mycobacterium and Listeria.[53]  Also, fungal infections are also more common and severe in T cell deficiencies.[53]

text: Cancer[edit]

text: Cancer of T cells is termed T-cell lymphoma, and accounts for perhaps one in ten cases of non-Hodgkin lymphoma.[54]  The main forms of T cell lymphoma are:

text:
Extranodal T cell lymphoma
Cutaneous T cell lymphomas:  Sézary syndrome and Mycosis fungoides
Anaplastic large cell lymphoma
Angioimmunoblastic T cell lymphoma

text: Exhaustion[edit]

text: T cell exhaustion is the progressive loss of T cell function. It can occur during sepsis and after other acute or chronic infections.[55][56]

text:
T cell exhaustion is mediated by several inhibitory receptors including programmed cell death protein 1 (PD1), TIM3, and lymphocyte activation gene 3 protein (LAG3).[57]
CD8+ T cell exhaustion occurs in some tumours, and can be partly reversed by blocking the inhibitory receptors (e.g. PD1).[58]

text: T cell exhaustion is associated with epigenetic changes in the T cells.[59]

text: ( See also Immunosenescence#T cell functional dysregulation as a biomarker for immunosenescence ).

text: Research[edit]

text: Genetic engineering[edit]

text: In 2015, a team of researchers led by Dr. Alexander Marson[60] at the University of California, San Francisco successfully edited the genome of human T cells using a Cas9 ribonucleoprotein delivery method.[61] This advancement has potential for applications in treating "cancer immunotherapies and cell-based therapies for HIV, primary immune deficiencies, and autoimmune diseases".[61]