Early Brain Development and Learning

It is not commonly known that the brain is 90% developed by age five. Most people believe that at age five children are just starting to learn. In fact, the brain absorbs more from birth to age five rather than from age five on. Parents and family can do many things to aid in the development of a baby’s brain, ultimately assisting in their learning. The sequence and rate at which the brain develops predicts the optimal times for a baby to learn. Sequence and rate is measured by milestones that a baby may reach by a certain age. Experiences are one thing that helps promote brain development. Our five senses give us these experiences. How in the first few years of life do we develop into the complex people we are today? We will look at how nature versus nurture; sensory perception; positive and negative experiences and both our social and physical environment contribute to and develop everything about whom we are as individuals. The brain is influenced in many different ways. The most important factors in brain development start with genetics, nutrition, and responsiveness from parents, daily experiences, and physical interactions. Parents need to know that children are learning and accepting more information that a fully grown adult. Children need positive and sensitive feedback from family. In the past, scientist believed that the human brains development was determined by a biologically determined path (Brotherson, 2005). This means that the brain would develop genetically through family, but leading technology and science proved that the brain is not predetermined genetically by family. The brain matures through the five senses: smell, touch, vision, taste, and hearing. The experiences that the five senses bring are very crucial to help build the connections that guide brain development. The importance of the parents understanding of the first few years of his or her child’s life is extremely important. As Titzer, P. H. D, (2008) uses a computer metaphor to explain brain development he put it this way â€Å"Your baby’s brain could be thought of as a highly responsive, self-programming computer. For the first few years, the hardware is still coming together – a baby is not a finished product, but a growing, developing individual, complete with organic â€Å"circuitry† – the central nervous system† (p. ). The brain will absorb more with more stimulation. At an earlier age stimulation for the brain circuitry is at its best. This will cause the brain circuitry to develop more effectively. The main function of the brain in the first three years of life is to create and support connections between neurons. The con nections are referred to as synapses. Synapses could be envisioned as the limbs on the tree. Imagine a large family tree with its trunk as the original lineage. Then the main branches are the families as they grow and have children. Neurons are like the trunk and the main branches of the tree. The number of neurons a baby is born with remains constant in the first three years of life. Synapses (all those years of lineage on the family tree) are all the little twigs and branches that come off the main trunk. In the first three years of life our brains synapses increase to a number in the hundreds of trillions. However, after age three the number of synapses begins to slow until age 10. During this period there are more synapses created than needed. A person creates more synapses than needed and the â€Å"use it or lose it† theory applies to all the unused synapses. The synapses being used the most, meaning the circuits that transfer information the most become permanent to the brain. The synapses not used are lost in a process called pruning. In fact, the ability to see light is lost if the eyes are not exposed to light within the first three weeks of life, hence â€Å"use it or lose it† theory (Hawley, 2003). This will happen because the synapses that can see light will be lost because they will not have been used. That is why we want to give our children as much experience socially and with learning as possible. With this kind of experience these synapses will become permanent. Brotherson (2005) describes a baby’s brain at this point like a â€Å"†super sponge† absorbing everything given to it (para. 4) The first three years are the most sensitive for learning and development (Gable & Huntington, 2001). The brain takes in these experiences through our five senses. According to Gable & Huntington (2001) â€Å"an infant’s social, emotional, cognitive, physical and language development are stimulated during multisensory experiences† (para. 12) During these first few years of life is most rapid growth period for the brain. At birth the brain is 25% developed, at six months it is 50% developed , at 30 months 75% developed and at age five it is already 90% developed. There have been many optimal opportunities for parents to teach their children many things from birth to this point already. Children at the age of two have been known to read at the reading level of a fifth grader because they were taught at the â€Å"prime time. † Acquiring the knowledge of how a baby’s brain develops and what can be done to influence it in a positive way can make a world of difference for a child. A positive influence during this critical period is very crucial. Let us take a look at nature versus nurture; sensory perception; positive and negative experiences and both our social and physical environment contribute to and develop everything about who we are as individuals. Take the study of nature, for example, our individual innate qualities versus nurture, and our personal experiences. As evidences by the recent Human Genome Project, it is currently believed that there is much more nurture than nature in the result of each of us. With this, how does nurture become nature? Let us look at the example of ‘perfect pitch’ to show the relationship between genetics and environment. This is an example of how† heredity and environment can interact† (Davies, 2001, para. 3). Davies (2003) describes perfect pitch as â€Å"The ability to recognize the absolute pitch of musical tone without any reference note. People with perfect pitch often have relatives with the same gift and research show this is a highly inherited gift, possibly the result of a single gene. However, studies also demonstrate a requirement for early musical training (before age 6) to manifest perfect pitch. Many personality and behavioral traits will not be exclusively the result of nature or nurture, but rather an inextricable combination of both† (para. 5). _ Nature versus nurture and the role that heredity and environment have in human development indicates that with almost all biological and psychological traits genes and environment work together in communication back and forth to create us as individuals . No one questions it; this is the ying and the yang, the Adam and Eve, the Mom and Pop of pop psychology and genealogy. Nature and Nurture is what made us what we are today and will determine what our children will be tomorrow. I have heard the expression that life is all about perception. We all know people who are positive and those who are negative. And each of us has either an optimistic or pessimistic personality. How we perceive the world around us is i nherently a matter of our sensory perception of the world and largely that done in the first several years of life. We have many senses but we most often refer to the five senses of sight, hearing, smell, touch and taste. We are born with the need for a multisensory environment. Research shows that interactions that are associated with many of emotion are more â€Å"readily remembered and recalled†_ __(Gable & Huntington, 2001, para. 17)_. With this, it is proven that with a multisensory environment we develop out temperament and emotions during an early the early stages of life. Developmental milestones are certain things that a child should be able to do by a certain age range. A child’s doctor will use these milestones to assess the development of a child in the area of his/her gross motor, fine motor, language, cognitive, and social skills. Even though each milestone has an age range, each child is different and unique so the age can vary significantly. One child may start to walk as early as seven months old and another child may not begin to walk until 16 months old and both would be considered normal. They both would be within the normal age range. In conclusion, we have looked at how genetics and environment in early brain development occurs as well as the importance of multiple sensory experiences, positive interactions, and social and physical stimulation in early development of a variety of cognitive and behavioral skills. It was briefly discussed that there are many interventions and treatments for improvement in many areas of interrupted brain development due to early childhood trauma, stress, and neglect with appropriate intervention. Many agencies today focus on education for parents and caregivers to ensure a more positive and educational experience for the early brain development. References Brotherson, Gable,S. & Hunting, M. (2001). Nature, Nurture and Early Brain Development. Retrieved from http://extension. missouri. edu/publications/DisplayPub. aspx? P=GH6115 Hawley, T. (2003). Starting Smart. How Early Experiences Affect Brain Development. Titzer, R. Ph. D. (2008). Your Baby Can Read. Carlsbad, Ca

Biblical Judaism essays

Biblical Judaism essays The Hasmonean dynasty can be considered to be a turning point in the history of the biblical Jewish ancient state. It represented the time in history that marked two important moments in the Jewish culture: on the one hand, the end of the Maccabean Wars, and on the other hand, the start of the Roman rule over Palestine. The most important contribution of the reign of the Hasmonean dynasty was the period of development for the Jewish people. One of the most visible changes that took place at the time was the territorial expansion of the state. In this sense, The policy of conquest carried out by the Hasmoneans led to a major expansion of Jewish territory, achieved by expulsion and dispossession of non-Jewish population groups. In principle, these new territories became the property of the ruler, that is, the reigning family, just as was the case under the Hellenistic monarchies (Schfer, 2003). From this point of view it can be said that the dynasty played an important role in establishing the Jews as a unitary group on a definite territory. Another major role played by the dynasty was in the creation of a standing army of the Jewish state. With the use of mercenaries as part of their army, this allowed them to be in better control of their land and territory, both to protect him from outside threats, as well as to maintain its unity in the face of internal threats. Also during the Hasmonean Dynasty, the political scene changed as the Pharisees became an ever increasing force. Thus, while under Alexander Jannaeus, the Pharisees were subjected to outright persecution, under Jannaeus' successor, Salome Alexandra, they apparently rose to become the dominant party in the state (Schfer, 2003). Afterwards, new parties, that of the Zealots also emerged. However, the start for a certain type of political life became fully visible during the Harmonean Dynasty and from this point of view, it represents one of t...

Banking System and Macroeconomic Effects †MyAssignmenthelp

Crypto currencies are forms of digital currency. These currencies use encryption techniques in order to regulate the generation of currency units. Bitcoin is one such crypto currency. Crypto currency is not yet considered as a legal tender in most countries. In fact, at present most of the central banks of the world are putting efforts to ban the trade of crypto currencies. Over the last few years, certain crypto currencies like Bitcoin have garnered immense attention from across different traders owing to their volatile nature. Bitcoin was introduced in the year 2009. The currency is traded without a middleman and with zero bank involvement. It is a peer to peer network through which this currency is traded and transactions are made directly to the parties. Bit coin can be used to trade in goods and services, some use it as a form of investment and some are using it for making payment of businesses (Popper, N., 2015). However, most countries have yet not accepted it as a legal payme nt methodology. It is similar to digital cash transaction as Bitcoin can also be sent through mobile applications and puters. Bitcoin is stored in a digital wallet. These wallets are used as a virtual bank account that allows users to save, send and receive their payments. These wallets are not recognised by the FDIC as methods of paying for goods or services. Bitcoin works as a medium of exchange for goods and services in four countries at the moment which are Japan, Canada, Germany and Holland. Bitcoin is considered to be a form of currency as it can be stored for future investments (Forrester and Solomon, 2013). Bitcoin investment of an individual can also reflect upon the purchasing power of consumer. Consumer have the option to buy the currency, hold it in their accounts or book profits as they deem profitable depending upon the volatility in the market (Bit coin, 2018). Merchants who accept Bit coin as a payment can convert it into standard currency that is in Dollars, Euros etc. Bitcoin has some advantages as it introduces a new payment mechanism; tipping system, automated payment solution, time locked payment management, public asset tracking, low trust escrow services, micro payment channels and more such facilities (Bit coin, 2018). Another advantage of Bitcoin is that its high volatility in the currency market makes it a ‘high risk and high return’ asset. Pegging any currency against the dollar refers to the act of fixing the currency value with respect to the value of Dollar. In other words we can say that the value of US dollar against the other currency is fixed and will not move irrespective of how the market functions. The process of pegging currency with US dollar is often conducted in oil extracting countries as US is the largest importer of oil. GCC economies are the third largest economy. The growth of this economy is highly dependent on selling oil (The Economist, 2018). By pegging the GCC against Dollar has several advantages and disadvantages. Pegging of currency eliminates the risk of currency fluctuations and the risks associated with it. This provides stability to the currency in the international currency market. Pegging encourages the regional currency valuation as the dollar is considered to be the standard currency and by pegging with dollar, currency of other country does not fluctuate (Brooking, 2018). In countries like Saudi Arabia and Venezuela pegging with US dollar has been done in order to protect the countries from the risk of currency fluctuations because US is the major importer for oil. Various countries opt for pegging in order to increase external trade in the country. As external trade increases, the GDP of the country also increases. When pegging of a currency is done to a higher value currency then the value of the country enhances in the public opinion making it an attractive destination to invest. Therefore investment b es easier in that country. This process also protect country from speculation Pegging also gives freedom to set rules and economic policies, interest rates and help to control inflation in the country. Therefore countries must peg their currencies to dollar in order to limit their risks. If a country currency is pegged with the US dollar then the country can take more loan as it will have a more stable environment and economy. Pegging also helps in getting better deals for international loans and interest rates provided the economy’s inflation is in control. The loan taken in the dollar value is harder to pay off because dollar has the high value as pared to the other currency. Therefore in the longer run, pegging would result in rising cost of capital and increased import prices (Espinoza and Prasad, 2010).   The country which pegs it’s currency with the USD has to maintain a high reserve of dollars. It means central bank of that country has to hold a high amount of reserves in US dollars (Financial Times, 2018). Holding of foreign currency reserve (dollar) indulges a cost which adversely affects the economy. Pegging also leads to an increase in inflation. Growth and development of a country is dependent on the performance of dollar. Monetary policies are restricted in every country and are wholly dependent on the performance of the currency to which the currency is pegged. Similarly in the case of US dollar and countries pegged with it, it means that if the value of US dollar falls the currency of other country will also fall and vice versa. Bitcoin, 2018. ‘Bit coin for developers’. [Online]. Available at:   https://Bit coin.org/en/Bit coin-for-developers [ACCESSED ON 30 th march 2018] Bitcoin, 2018. ‘Bit coin for individual’. [Online]. Available at:   https://Bit coin.org/en/Bit coin-for-individuals. [ACCESSED ON 30 th march 2018] Brooking, (2018). ‘Sustaining the GCC currency pegs: The need for collaboration’. [Online]. Available at: https://www.brookings.edu/research/sustaining-the-gcc-currency-pegs-the-need-for-collaboration/. [ACCESSED ON 31 th march 2018] Espinoza, R.A. and Prasad, A., 2010.  Ã¢â‚¬ËœNonperforming loans in the GCC banking system and their macroeconomic effects (No. 10-224)’. International Monetary Fund. Financial Times, 2018. ‘Gulf’s dollar peg makes sense’. [Online]. Available at:   https://www.eiu /industry/article/1725886356/will-the-gulf-co-operation-council-currency-pegs-survive/2017-09-13. [ACCESSED ON 31th march 2018] Forrester, D. and Solomon, M., 2013.  Ã¢â‚¬ËœBitcoin explained: Today's plete guide to tomorrow's currency’. CreateSpace Independent publishing platform. Popper, N., 2015.  Digital gold: Bitcoin and the inside story of the misfits and millionaires trying to reinvent money  (pp. 156-197). New York: Harper. Tanha, H. and Dempsey, M., 2017. Derivatives usage in emerging markets following the GFC: Evidence from the GCC countries.  Emerging Markets Finance and Trade,  53(1), pp.170-179. The Economist, 2018. ‘Financial Services’. [Online]. Available at:   https://www.eiu /industry/article/1725886356/will-the-gulf-co-operation-council-currency-pegs-survive/2017-09-13. [ACCESSED ON 30 th march 2018]. The National, 2018. ‘Why GCC states should ditch the dollar peg and switch to a currency basket’. [Online]. Available at: https://www.thenational.ae/business/economy/why-gcc-states-should-ditch-the-dollar-peg-and-switch-to-a-currency-basket-1.700668. [ACCESSED ON 31 th march 2018]

The last financial crisis 2007-2009 has many implication on different Term Paper

The last financial crisis 2007-2009 has many implication on different markets , however there are some arguments that the gulf a - Term Paper Example Granting of loans in an uncontrolled manner, which resulted in the value of the loan exceeding that of the assets, was the root of the problem. These loans were provided to the borrowers without conducting a minimum check on their credit-worthiness. The result was that many of the borrowers failed to pay their loans back, which clearly reflected the financial status of the institutions and their inability to pay their obligations, thereby resulting into collapse. This paper investigates the severity of the impact on the GCC market. In this context, the financial market of the GCC countries has been considered along with special attention towards Qatar. The study revealed that the severity of the impact was not as huge as compared to the rest of the world. This can be due to the fact that the policy makers of GCC countries took ardent steps to mitigate the risk. Moreover, the Qatari economy did not get much affected and the banks were declared solvent in that time. However, the real e state business was seen to experience huge hit by the credit crunch. 1. Introduction In the year 2008 and 2009, the global economy was rocked by the financial crisis which was considered as the most devastating economic event, after the Great Depression in 1930s. The aftermath of this global crisis was felt in every part of the world. The global crisis was initiated by the low interest rate regime along with huge inflow of foreign funds that led to the housing construction boom and encouraged large consumption of debt-financing in USA. The Federal Government of United States made it possible for almost everyone to own a home by giving 1 percent rate on the mortgages. The loans that included the mortgages were given to almost everybody without checking the credit worthiness of the borrowers (Sivakumar and Krishnaswami, 2012). With the decline in the housing prices, the major financial institutions, which were involved in borrowing for investing in the subprime MBS, had reported signi ficant loss. This decrease in the price also resulted in a fall in the prices of the homes that worth less than the mortgage loans, which incentivised financially the entry towards the foreclosure. Towards the end of 2008, the crisis peaked. Several banks and other financial institutions of Europe and USA failed as a result of this crisis and governments were trying hard to save these institutions by bailing them out (Kasekende, Ndikumana and Rajhi, 2009; Anon., 2009). The crisis started propagating beyond its epicentre, thereby affecting not only the advanced economy, but also the emerging economies and the rich Arab GCC countries. This paper aims to analyse the degree of impact on the GCC countries. In this context, the paper will specially analyse the situation in Qatar and other GCC countries. 2. Literature Review 2.1 Evolvement and Concept of Global Financial Crisis The term financial crisis refers to the sudden reduction in the price of the assets, which can be financial, such as, bonds and shares and can even be materials like, equipments and machinery. This sudden reduction can result from the price bubble which indicates an abrupt and huge increase in the prices ending in a sudden collapse. Moreover, the bankruptcy of Lehman Brothers, the giant financial institu

Book Review on Economic Sophisms, by Frdric Bastiat Essay

Book Review on Economic Sophisms, by Frdric Bastiat - Essay Example This argument is extended to high tariffs, because these tariffs do not benefit the consumer, only the manufacturer. Discussion Bastiat begins the argument by examining the theory of scarcity verses the theory of abundance. One of the arguments that protectionists put forth is that free trade causes a surplus of goods, and that this will drive down the price of goods sold. Bastiat refutes this argument by noting that, while the theory of scarcity does benefit the producers, the consumers are benefited when goods are abundant, and that, if man did not operate by the exchange of goods, abundance would be more beneficial to him in the long run (Bastiat, 1964, p. 10). Bastiat takes issue with the analysis of protectionists because it so heavily favors the side of the producers, while not looking at the perspective of the consumers. Protectionism produces scarcity and lessens the obstacles to production for the producers, but the consumer, who will have to pay higher prices because goods are scarcer, is not considered in the equation (Bastiat, 1964, p. 29). Further, Bastiat takes issue that the success of the foreign competitor will mean the failure of the domestic firm, even if the foreign competitor has better conditions to produce the commodity. ... However, Bastiat rejects this argument. Rather, Bastiat argues that each competitor can produce according to how strong he is, but it does not mean that one succeeds and one fails (Bastiat, 1964, p. 30). Furthermore, such an arrangement, where country A produces a commodity cheaper than country B, and is allowed to freely export the commodity into country B, benefits the consumers, and Bastiat sees this as an appropriate ends to the means (Bastiat, 1964, p. 42). A further error refuted by Bastiat, which is related to the previous error that countries do not have equal conditions of production, therefore protectionism is valid to protect the domestic firms from cheap imports, is that high taxes are needed on foreign imports to equalize the costs of goods. This is especially true when the targeted country has high domestic taxes. If the domestic taxes are high, then foreign tariffs must also be high. If this were not true, the domestic products would be substantially more expensive, du e to the high taxes, and would therefore be less desirable to consumers to buy then the foreign competitors. Bastiat refutes this by pointing out that the people get a return on their investment in these domestic taxes, through the building of roads, bridges and the like. However, the protectionist tariffs, argues Bastiat, are not for the good of the people, but for the producers. Yet the people pay to subsidize the firms. Further, free trade benefits the people, because exporting French goods means that other countries are paying the taxes that the French would be paying (Bastiat, 1964, pp. 48-49). Bastiat also makes the argument that protectionists are, essentially, making the

Public Policy and Law Essay Example | Topics and Well Written Essays - 3000 words

Public Policy and Law - Essay Example The Equal Employment Opportunity Commission (EEOC) has discovered several major weaknesses in the anti-harassment policies and processes in many agencies. This essay discusses the definition of sexual harassment, as well as the relevant laws, case laws, and the current figures and scenarios. Introduction Cases of sexual harassment in the workplace is well documented and widely known. Catharine MacKinnon led the campaign for sexual harassment to be acknowledged as a rightful issue under the 1964 Civil Rights Act’s sex discrimination requirements (Mink 64). Before sexual harassment was acknowledged by the U.S. Supreme Court as a valid type of sex discrimination forbidden by federal law in its resolution in Meritor Savings Bank v Vinson in 1986, numerous lower courts had wrestled with the difficult problems posed by sexual harassment (Mink 64). Numerous lower courts had declined to acknowledge sexual harassment as a valid ‘cause of action’, claiming that courts shoul d not investigate or examine explanations of human conduct in the workplace. Human conduct or behavior, according to these courts, embodied a ‘slippery slope’ that would require a much larger number of federal judges, or that it would dramatically increase the number of court cases (Achampong ix). The invalidation of these decisions was an acknowledgment of the reality that sexual harassment is a criminal conduct that brings about a valid cause of action. Definitions, Relevant Laws, and Case Laws The 1990s have witnessed a sharpened awareness in society about sexual harassment, and a persistent, very important move toward total prevention of sexual harassment in the workplace (Bakirci 17). However, there is no direct and simple definition for sexual harassment. However, any definition in any policy should be clear and straightforward without leaving out the key legal principles (Orlov & Roumell 61): Sexual harassment is against the law. Any conduct of a sexual nature wi th or between coworkers or other managers could be considered sexual harassment. Anyone who breaks the law will be punished. All policies pertaining to sexual harassment must explicitly define that sexual harassment is a type of sexual discrimination prohibited by Title VII of the 1964 Civil Rights Act or federal employment discrimination laws and nearly all other anti-discrimination laws. The policies of the Equal Employment Opportunity Commission (EEOC) policies sexual harassment must be used. Most companies integrate them into their guidelines because they provide a quite precise and definite legal description of sexual harassment. The EEOC defines sexual harassment in this way (Achampong 201): Unwelcome sexual advances, requests for sexual favors, and other verbal or physical conduct of a sexual nature constitutes sexual harassment when (1) submission to such conduct is made either explicitly or implicitly a term or condition of an individual’s employment, (2) submission to or rejection of such conduct by an individual is used as the basis for employment decisions affecting such individuals, or (3) such conduct has the purpose or effect of unreasonably interfering with an individual’s work performance or creating an intimidating, hostile, or offensive work environment. Nevertheless, any definition of sexual harassment must not end with the EEOC policies. They are simply the basis for a definite and brief definition. The various forms of sexual harassm

T Cell Receptor and the B Cell Receptor: Comparison

T Cell Receptor and the B Cell Receptor: Comparison The entire world is full of pathogens which we need to fight off to leave a normal life. Due to this, we have an immune system that helps us fight off and prevent/manage subsequent infections. Our immune system can be classified into two, the innate and acquired immune responses. The innate immune response is broadly specific and provides the first defensive action against any infection. Their response to any subsequent infection stays the same as the initial infection. In contrast, the acquired immune response is highly specific such that it provides defence by generating antibodies specific to an antigen. They also have the capacity of keeping infection memory such that there will be a more powerful response to future infections. Innate immune response is mostly provided by macrophages, dendritic cells, polymorphonuclear leukocytes, mast cells, natural killer cells, erythrocytes and platelets. The acquired immune response is provided by lymphocytes, the T (T cells) and B lymphocyte s (B cells). The lymphocytes are derived from hematopoietic stem cells (HSC) in the bone marrow. That form MLPs (myeloid-lymphoid progenitors). If the HSC and MLP stay in the bone marrow they form B cells and if they migrate (via blood) to the thymus they form T cells (see figure below). Initiation of immune response by the lymphocytes first requires recognition of the antigens and this is achieved by cell surface receptors called BCRs (B cell receptor) and TCRs (T cell receptor). These two receptors have great similarities and differences in their structure complexes, antigen recognition, cell activation and genetic recombination. A) STRUCTURE OF BCRs AND TCRs Both the BCR and TCR have great similarities and differences in the structure. They both exist as multi-chain complexes as seen in the diagrams below: i) Antigen recognition components In the figure above, section A shows the structure of a BCR. The BCR antigen recognition medium is an immunoglobulin (Ig) molecule (a transmembrane antibody). The antibody is modified via alternative splicing that adds a hydrophobic transmembrane domain and a short cytoplasmic domain (~3 aminoacids) at the C terminus of the immunoglobulin heavy chain (Wall Kuehl 1983). All naà ¯ve B cells only express both IgM and IgD classes of immunoglobulin but do switch to other classes upon activation by antigens (Goding, 1978). The antibody (figure 2C) is a highly specific Ig that can adopt any one of the 5 immunoglobulin isotopes, IgG, IgA, IgM, IgD and IgE. The antibody has 3 regions of which 2 regions (FAB) vary from antibody to antibody and bind to antigens and 1 region (FC) that binds to effector molecules. The antibody is composed of 2 light and 2 heavy chains held together by inter and intra disulphide bonds. The heavy chains depending on the Ig isotypes can be any one of ÃŽÂ ³, Ã⠀šÃ‚ µ, ÃŽÂ ±, ÃŽÂ ´ or Ɇº chains. The variable domains (VH and VL) bind to antigen and also bring about variability and antigen recognition specificity. This specificity is mainly due to the presence of 3 hypervariable regions (Complementary Determining Regions), namely CDR1, CDR2 and CDR3 in the variable regions. Similar to BCR, the antigen recognition medium in TCR is an immunoglobulin heterodimer made from ÃŽÂ ± and ÃŽÂ ² Ig chains (in most T cells) or ÃŽÂ ³ and ÃŽÂ ´ Ig chains. Unlike in BCRs where the IG can be of 5 types, in TCRs the Ig heterodimers are only of 2 types. The two Ig chains in TCRs are (also like BCRs) held together by intra and inter disulphide bonds. As seen in section C, each Ig chain folds into 2 domains, the variable and the constant domain. This folding greatly resembles the FAB region of the antibody in BCRs. Likewise antibodies, the ÃŽÂ ±ÃƒÅ½Ã‚ ² and ÃŽÂ ³ÃƒÅ½Ã‚ ´ heterodimers also have hypervariable regions (CDR1, CDR2 and CDR3) in variable domains. The variable regions in both BCRs and TCRs bring about specificity and diversity The BCR antibodies have a hinge joint (connecting FAB and FC) that makes the Ig molecule very flexible. Unlike antibodies, the flexibility of the TCR Ig molecule is very limited at the elbow region (junction of constant and variable region) (Degano et al, 1996). ii) ACCESSORY PROTEINS Both the BCR and TCR have very short cytoplasmic domains that restrict the binding of any signal transduction factors to the receptors. Due to this the receptors are unable to transducer signals into cells upon antigen recognition. Signal transduction is achieved via the accessory proteins. BCRs (figure 2 section A) accessory proteins consists of one or more dimmers of one each of Ig-ÃŽÂ ± and Ig-ÃŽÂ ² chains held together in the cell membrane by a pair of disulphide bonds. The cytoplasmic domains of these chains have phosphorylation sites called ITAMS. Unlike BCR accessory protein, the TCR accessory proteins (figure 2, section C) is composed of a complex know as CD3. It consists of 3 types of invariant chains, namely ÃŽÂ ³, ÃŽÂ ´ and Ɇº. A ÃŽÂ ³ or ÃŽÂ ´ chain couples up with one Ɇº chain (by formation of disulphide bonds) each to form two dimmers (ÃŽÂ ³Ãƒâ€°Ã¢â‚¬ º and ÃŽÂ ´Ãƒâ€°Ã¢â‚¬ º). In addition to this, a dimmer of 2 zeta (ÃŽÂ ¶) chains is also present. Together, these 3 dimers make up the CD3 complex. The ÃŽÂ ¶ chains have a much longer cytoplasmic tail than the ÃŽÂ ³, ÃŽÂ ´ and Ɇº chains and have 3 ITAMs as compared to one in the ÃŽÂ ³, ÃŽÂ ´ and Ɇº chains. Therefore for both BCR and TCR accessory proteins are dimmers that all contain ITAMs. B) GENERATION OF RECEPTOR DIVERSITY There are millions antigens and we need to produce millions of antibodies against them. However, we do not have millions of Ig genes so how are we able to produce all these different antibodies? The answer is antibodies are produced in developing B cells via genetic recombination of genes encoding the immunoglobulins (Hozumi and Tonegawa, 1976). The figure below shows the gene segments coding immunoglobulins. Figure legend: The human heavy chain locus as shown in the last row, consists of about 38-46 functional VH genes, 27 DH and 6 JH genes. The light chain can be either made of ÃŽÂ » or ÃŽÂ º chains. The ÃŽÂ » locus consists of about 30 functional V ÃŽÂ » genes and 5 J ÃŽÂ » genes each separated by a J segments. The Kappa locus has about 34-40 functional VÃŽÂ º genes and 5 JÃŽÂ º genes. The variable heavy chain region of the antibody is made from the joining of the V (variable), D (diversity) and J (joint) gene segments and the variable light chain (which can be either ÃŽÂ º or ÃŽÂ ») is formed from the joining of V and J segments only. A process called V(D)J recombination involves joining different gene segments and as a result bringing about antibody diversity. At the heavy chain locus, any one of the 27 D and 6 J gene segments are first joined together and then any one of 46 V gene segment is joined to this DJ segment. This rearranged DNA is then transcribed to form a primary mRNA. This mRNA then undergoes splicing to bring the VDJ segment close to the constant gene segment. Additional diversity is achieved as any 1 of the two types of light chains can be formed. Random insertion of nucleotides either side of D segments also creates N-nucleotide diversity. In total about 106 possible immunoglobulin gene combinations can be formed. This recombination process is driven by recombination signal sequences that flank the coding gene segments. Certain enzymes (RAG-1 and RAG-2) help mediate this somatic recombination process. The antibodies produce undergo a processs of clonal selectin where only the antibody specific to the antigen preferentially proliferates to make many antibodies. Binding affinity of BCR is greatly increased after antigen recognition where the variable regions of both heavy and light chain undergo somatic hypermutations. This is where point mutations are put in the variable regions of rapidly proliferating B cells. These mutations produce antibodies that may have good, moderate or good affinity for the antigens. The antibody with good affinity will have a selective advantage during clonal selection. The gene segements encoding TCR ÃŽÂ ² chain follow the similar V,D,J and C arrangement of BCRs. The recombination process involves of of the two DÃŽÂ ² genes rearranges next to one of JÃŽÂ ² genes. Then one of the ~50 V genes arranges next to the preformed DÃŽÂ ²JÃŽÂ ² genes. As seen , this is also similar to the B cells where a DJ segement forms first and then joins up with a V segment. There is also random insertion, just like in B cells, of nucleotides either side of D segments to create N-nucleotide diversity. Unlike in B cells, there is no somatic hypermutation in T cells after antigen recognition. If this occurs, the TCR will loose its ability to recognise MHC and the peptide it presents. C) ANTIGEN BINDING/RECOGNITION BCR and TCR have similar immunoglobulin antigen recognition receptors but the types of antigens they recognise are very different. BCR can recognise naÃÆ' ¯ve (as a whole) antigens and TCR can only recognise a single antigen peptide sequence presented onto cell surfaces by MHC (Major histocompatibility complex) molecules. The antigens recognised by B cells are naÃÆ' ¯ve and therefore the antibody in BCR mostly recognise discontinuous epitopes on the antigen and antigens recognised by the TCR is in form of linear peptide sequences and therefore they mostly recognise continuous or linear epitopes. Antigen recognition by BCR is very simple where the antibody variable region simply recognises specific epitopes on antigen and bind to it. The BCR can recognise 3 types of antigens, Type 1 thymus independent antigens (where bacterial lipoproteins can bind to mitogenic bypass molecules on B cells surface and this allows non-specific antigen B cell activation), Type 2 thymus independent antigens (appiles to antigens that have well spaced and repetitive polysaccharides that bind to multiple antibodies in BCR and activate the B cell) and Thymus dependent antigens (require helper T cells). Thymus dependent antigens when bind to TCR, instead of causing activation normally cause anergy. Due to this, once the binding has occurred, the whole antigen+TCR comples is endocytosed, the antigen is hydrolysed by enzymes and processed to small linear peptides and then presented onto the B cell surface via MHC2 molecules. Helper T cells then recognise this peptide-MHC complex. B cells have loads of C D40 on their surface that binds to CD40L present on Th helper cells. In response to this Th cells secrete IL-4, 5, 6 that also help activate other costimulatory molecules in the BCR coreceptor complex. All these events provide costimulation of the B cells and it is activated. ÃŽÂ ±ÃƒÅ½Ã‚ ² heterodimer TCRs in comparison can recognise any type of antigen that is processed and presented as a single peptide on MHC1 on target cells and MHC2 on B cells, macrophages and dendritic cells (all professional antigen presenting cells). The non-covalent forces that help TCR bind to the peptide-MHC complex are similar to the forces that enable the antibody bond to the antigen i.e. noncovalent. Unlike BCR that only have to recognise epitopes on antigens, the TCR has to both recognise the presence of both MHC molecule and antigen peptide. The TCR VÃŽÂ ± (variable alpha region) overlays ÃŽÂ ±2 helix of MHC1 or ÃŽÂ ²1 helix of MHC2 and the VÃŽÂ ² domain overlays ÃŽÂ ±1 helix in both MHC1/2. The CDR1 and CDR2 bind to ÃŽÂ ± helices of MHC and the CDR3 (which is more variable), binds to the antigen peptide on MHC. This concept is summarised in the picture below: Figure legend: The picture shows how the TCR variable complementarity determining regions (CDR) which are the binding sites interact with peptide-MHC complex. The CDR1 and CDR2 bind to the MHC alpha helices and CFR3 binds to the peptide. The ÃŽÂ ³ÃƒÅ½Ã‚ ´ TCRs are more similar to BCR antibody as they can recognise naÃÆ' ¯ve antigens without the requirement of processed antigen presentation. Another similarity of BCR and ÃŽÂ ³ÃƒÅ½Ã‚ ´ TCRs is that in the antibodies of BCRs, the CDR3 regions on heavy chain are shorter than the CDR3 in heavy chains and also the same in ÃŽÂ ³ÃƒÅ½Ã‚ ´ TCRs is seen where the ÃŽÂ ³ are shorter than the ÃŽÂ ´ CD3. COSTIMULATIONS Both lymphocytes do not get activated (but undergo anergy) once they recognise and bind to an antigen. They require costimulatory signals that will eventually lead to the activation of the lymphocytes. The B cells have BCR co receptor complex consisting of CD19 and CD21 (complement receptor), CD81 and LEU13 (interferon induced transmembrane protein 1). All these molecules are stimulated in presence of interferons and complements that give a costimulatory signal to B cells and activate it when it has recognised an antigen. The precise details of how these costimulatory molecules stimulate B cell signalling are still under investigation. In contrast to the 4 main costimulatory molecules in B cells, the primary costimulatory molecule in T cells is CD28 (figure besides) The binding of peptide-MHC to TCR causes up-regulation of certain molecules (e.g. CD28). T cells, like B cells can be costimulated by either cytokines or costimulatory molecule interactions. APC have surface molecules such as the B7.1 and B7.2 (or the CD80 and CD86) that recognise and bind to a molecule on the surface of the T cells called CD28 found on CD. This interacting provides co stimulation. The CTLA4 molecule is highly expressed after proliferation of the T cells. Once it binds to B7, instead of co stimulating T cells, it turns the T cells off. This is helpful in preventing excessive immune responses. No such regulatory mechanism is seen in B cells. A unique feature of T cells is that they have co receptors (CD4 and CD8) that help recognise the MHC molecules. CD4 molecules act as co receptors for MHC2 and are found on helper T cells and CD8 molecules present on cytotoxic T cells help recognise MHC1 molecules. ACTIVATION OF B AND T CELLS The activation of B and T cells following antigen recognition is somehow similar as it involves the phosphorylation of the ITAMS of accessory proteins. In B cells, antigen binding and co stimulation recruits the BCR+antigen to lipid rafts that brings protein tyrosine kinase Lyn close to the ITAMs of the cytoplasmic tails of the BCR associated proteins. Lyn phosphorylates ITAMs and triggers a signal cascade that results in increase of cytoplasmic calcium levels that activate transcription factors that control the entry of B cells into cell cycle. Eventually activate the B cells which then form plasma cells (that make loads of clones of antibodies to the antigen) and memory cells that will help manage subsequent infections. The initial proliferation of the activated B cell is accompanied by somatic hypermutation of the rearranged antibody variable genes that lead to the production of antibodies that may have poor, moderate or good binding capacity to the antigen. The good binding antib odies will be preferentially selected during clonal selection and they will further undergo proliferation to produce plasma and memory cells. A similar situation also occurs in T cells where there is activation of lipid rafts that bring the zeta chain ITAMS close to Lck (a protein tyrosine kinase) that phosphorylates the ITAMs and therefore create opportunity for other factors to bind to it and eventually cause mobilization of calcium that causes proliferation of T cell into Helper T cells, Regulatory T cells and Cytotoxic T cells.