Once class 12th results are out and the school is over, it is time to make the strategies for higher education and think over what to do next. With numerous options available today, students often get confused in choosing a relevant career path for them. Many of the students might have already had plans for their future in place but for some the confusion still persists.

Here are some tips to keep in mind while choosing the most relevant career path.

>Know your interests

Before jumping on to look for the available options in the science, commerce or humanities stream, it is extremely important to consider your interests. If you don’t want to spend your time at job/work counting your days then look for the career which best suits and aligns with your interests and abilities. Deciding out of peer pressure or family pressure might not turn out to be beneficial in long run.

>Choose the right course

These days there are a number of ways to pursue the same course such as degree course, diploma course, correspondence mode, online mode and distance mode of education. By getting to know about the course structure, syllabus and methodology of teaching you can pick up the course which suits your needs.

>Look out for future scope and opportunities

It might happen that your interests direct you to your preferred career path but not a viable career. In order to overcome this major hurdle, you need to search for and know about the future scope and opportunities available for that particular field in your country and abroad.

>Maintain a balance between college preference and course of study

A college preference might be as important as the preferred course but a balance between the two is more important. A good college offering your preferred course is a steal deal. However, if things don’t go as per your will, consider the course above the college brand. Because it is only the course that is going to decide your future prospects and not the college’s brand value.

>Have a plan B

Just in case you doubt losing the opportunity to grab your preference of course or college always have a plan B. It would not only save your time from being wasted but also let you to explore other options. Who knows the unexplored opportunities come with hidden but favourable outcomes for you.

In times like today, health has become the primary concern for all. Good immunity proportionates healthy living which comes from eating the right food in the right amount. Superfoods are the go-to food items for strong immunity and good health.

Superfoods are high in nutrition having very few calorie count. They contain high value of vitamins, minerals and naturally occuring antioxidants which keep your body disease-free and make you healthier. When taken in the right quantity in your diet, superfoods can improve heart health and increase energy level in the body, detox the body, regulate metabolism, lower body cholestrol, reduce cardiovascular disease risks and also help in weight reduction.

>Green leafy vegetables

Green leafy vegetable are a great source of many nutrients that boost our immunity such as vitamin A, C, E and K, calcium, iron, fibre, zinc, potassium, magnesium etc. The fibres and nutrients present in green leafy vegetables are found useful in preventing heart diseases, type-2 diabetes and certain chronic diseases. Some well known green leafy vegetables include kale, spinach, beet greens, watercress etc.

>Citrus fruits

Citrus fruits are rich source of vitamin C and B6, ribloflavin, calcium, magnesium and a variety of phytochemicals. These nutrients are responsible for improved gastrointestinal function and vascular protection. Also, consuming citrus fruits reduces risk of diabetes, cancer and neurological diseases. Examples of citrus fruits are orange, sweet lime, tangerine, kinnow,pomelo etc.

>Berries and cherries

Berries are rich in vitamin C, minerals, manganese and antioxidants and are also low in calories. They also contain flavonoids which are responsible for protection of body cells. Similar to berries, cherries are a great source of antioxidants which help in protection against viruses. Potassium rich berries are also good for improved blood pressure.

>Turmeric

Known for its antibacterial properties, turmeric is a very commonly found and well known ingredient in Indian households. It is rich in proteins, carbohydrates and minerals like manganese, potassium and phosphorous. Scientifically proven health benefits of turmeric include prevention of heart diseases, cancer, Alzheimer’s and prevent symptoms of depression and arthritis.

>Honey

Honey, which is often considered a substitute of sugar, is a rich source of ascorbic acid, pantothenic acid, niacin and riboflavin and minerals like iron, copper, zin, calcium, phosphorous etc. It is also rich in antioxidants and helps regulate blood pressure and has benefits on heart health.

>Yogurt

Yogurt provides to the body good amount of vitamin B12, minerals like calcium, riboflavin, phosphorous etc and proteins. The fermentation process used to make yogurt makes it healthier than milk and easy to digest which cause the nutrients to get absorbed by the body more easily and quickly. This not just improves digestive health but also helps in weight management, strengthens immunity and prevents bone diseases like osteoporosis.

Forced migration can be described as mass movement of people of a particular area out of threat to their lives and livelihoods. People unwilling to leave their home towns and countries are forced to migrate to nearby, or sometimes far away, cities, towns and countries to have access to better facilities.

In context to Uttarakhand, forced migration or distressed migration has arisen as one of the major issues in recent times. In particular, male-specific outmigration has become a trend in the hills. The people have been migrating not just to seek better employment but also to have access to better healthcare and educational facilities. The educated ones are the first to leave as they get good opportunities in the cities and settle there forever. However, the elderly population is not yet ready to leave their home land because of the affection and attachment to the place.

More than 5 lakh people have migrated from Uttarakhand within the last 10 years. According to 2011 census, a total of 1,18,961 people from 6,338 village panchayats have migrated out of Uttarakhand permanently, while 3,83,726 people have migrated in search of work and prefer to visit their native places in the hills frequently. Out of 16,500 villages in Uttarakhand, 734 have become ghost villages. Also, there are 664 villages with negligible population and 3,900 other villages in the state that have a population of 50 or less.

The state of Uttarakhand was formed in the year 2000 after separation from Uttar Pradesh to ensure development in the hilly region. Though the purpose doesn’t seem to be served yet. Well structured roads and good health facilities continue as the basic requirements of the people. The lack of educational facilities is also among the majors reasons of migration.

Moreover, the decreased fertility of soil is a major concern for the locals affecting the agricultural productivity. Since it is an ecologically fragile state prone to natural disasters with half of the population’s workforce on farm, scope for other employment opportunities reduces.

Changing time brings along changes in basic needs which might not be fulfilled by the traditional methods and style of Uttarakhand. It proves to be a major cause of the shift. People now prefer to settle in the cities permanently in order to enjoy the relaxing life and lucrative opportunities offered there as compared to their home towns in the hills where the daily routine is tough and hectic and a decent livelihood has become a challenge.

Joe Biden’s statement was at odds with the long-held US policy known as “strategic ambiguity,” where Washington helps build Taiwan’s defenses but does not explicitly promise to come to the island’s help.

Baltimore, United States: 

President Joe Biden on Thursday said the United States would come to the defense of Taiwan if the island were attacked by China, which considers it part of its territory.

“Yes,” he responded when asked in a CNN town hall about defending Taiwan. “We have a commitment to that.”

Biden’s statement was at odds with the long-held US policy known as “strategic ambiguity,” where Washington helps build Taiwan’s defenses but does not explicitly promise to come to the island’s help.

He made a similar pledge in August during an interview with ABC, insisting that the United States would always defend key allies, including Taiwan, despite the withdrawal from Afghanistan in the face of the victorious Taliban.

Biden said the United States made a “sacred commitment” to defend NATO allies in Canada and Europe and it’s the “same with Japan, same with South Korea, same with Taiwan.”

The phenotype (from Greek o- (faino-)’showing’ and (tpos) ‘type’) is a set of observable features or qualities of an organism in genetics. The phrase refers to an organism’s morphology, or physical shape and structure, as well as its developmental processes, biochemical and physiological features, behaviour, and behavioural outcomes. The expression of an organism’s genetic code, or genotype, and the effect of environmental variables are the two primary components that determine its phenotype. Both factors may interact, altering phenotype even more. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic.

Phenotypic variation

Phenotypic variation (due to underlying heritable genetic variation) is a fundamental prerequisite for evolution by natural selection. It is the living organism as a whole that contributes (or not) to the next generation, so natural selection affects the genetic structure of a population indirectly via the contribution of phenotypes. Without phenotypic variation, there would be no evolution by natural selection.

The interaction between genotype and phenotype has often been conceptualized by the following relationship:genotype (G) + environment (E) → phenotype (P)

A more nuanced version of the relationship is:genotype (G) + environment (E) + genotype & environment interactions (GE) → phenotype (P)

Genotypes often have much flexibility in the modification and expression of phenotypes; in many organisms these phenotypes are very different under varying environmental conditions (see ecophenotypic variation). The plant Hieracium umbellatum is found growing in two different habitats in Sweden. One habitat is rocky, sea-side cliffs, where the plants are bushy with broad leaves and expanded inflorescences; the other is among sand dunes where the plants grow prostrate with narrow leaves and compact inflorescences. These habitats alternate along the coast of Sweden and the habitat that the seeds of Hieracium umbellatum land in, determine the phenotype that grows.

An example of random variation in Drosophila flies is the number of ommatidia, which may vary (randomly) between left and right eyes in a single individual as much as they do between different genotypes overall, or between clones raised in different environments.^{[citation needed]}

The concept of phenotype can be extended to variations below the level of the gene that affect an organism’s fitness. For example, silent mutations that do not change the corresponding amino acid sequence of a gene may change the frequency of guanine–cytosine base pairs (GC content). These base pairs have a higher thermal stability (melting point) than adenine–thymine, a property that might convey, among organisms living in high-temperature environments, a selective advantage on variants enriched in GC content.

The extended phenotype[edit]

Main article: The Extended Phenotype

Richard Dawkins described a phenotype that included all effects that a gene has on its surroundings, including other organisms, as an extended phenotype, arguing that “An animal’s behavior tends to maximize the survival of the genes ‘for’ that behavior, whether or not those genes happen to be in the body of the particular animal performing it.” For instance, an organism such as a beaver modifies its environment by building a beaver dam; this can be considered an expression of its genes, just as its incisor teeth are—which it uses to modify its environment. Similarly, when a bird feeds a brood parasite such as a cuckoo, it is unwittingly extending its phenotype; and when genes in an orchid affect orchid bee behavior to increase pollination, or when genes in a peacock affect the copulatory decisions of peahens, again, the phenotype is being extended. Genes are, in Dawkins’s view, selected by their phenotypic effects.

Other biologists broadly agree that the extended phenotype concept is relevant, but consider that its role is largely explanatory, rather than assisting in the design of experimental tests.

Epigenetics is the study of heritable phenotypic modifications that do not entail DNA sequence changes in biology. [1Epigenetics is defined by features that are “on top of” or “in addition to” the usual genetic foundation for heredity. The Greek prefix epi- (- “over, outside of, surrounding”) denotes traits that are “on top of” or “in addition to” the traditional genetic basis for inheritance. Modifications in gene activity and expression are the most common epigenetic changes, although the phrase can also refer to any heritable phenotypic change. External or environmental influences may have an effect on cellular and physiological phenotypic features, or they may be a normal aspect of development.

Molecular basis

Epigenetic changes modify the activation of certain genes, but not the genetic code sequence of DNA. The microstructure (not code) of DNA itself or the associated chromatin proteins may be modified, causing activation or silencing. This mechanism enables differentiated cells in a multicellular organism to express only the genes that are necessary for their own activity. Epigenetic changes are preserved when cells divide. Most epigenetic changes only occur within the course of one individual organism’s lifetime; however, these epigenetic changes can be transmitted to the organism’s offspring through a process called transgenerational epigenetic inheritance. Moreover, if gene inactivation occurs in a sperm or egg cell that results in fertilization, this epigenetic modification may also be transferred to the next generation.

Specific epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, DNA methylation reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning.

DNA damage

DNA damage can also cause epigenetic changes. DNA damage is very frequent, occurring on average about 60,000 times a day per cell of the human body (see DNA damage (naturally occurring)). These damages are largely repaired, but at the site of a DNA repair, epigenetic changes can remain. In particular, a double strand break in DNA can initiate unprogrammed epigenetic gene silencing both by causing DNA methylation as well as by promoting silencing types of histone modifications (chromatin remodeling – see next section). In addition, the enzyme Parp1 (poly(ADP)-ribose polymerase) and its product poly(ADP)-ribose (PAR) accumulate at sites of DNA damage as part of a repair process. This accumulation, in turn, directs recruitment and activation of the chromatin remodeling protein ALC1 that can cause nucleosome remodeling. Nucleosome remodeling has been found to cause, for instance, epigenetic silencing of DNA repair gene MLH1. DNA damaging chemicals, such as benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene, cause considerable hypomethylation of DNA, some through the activation of oxidative stress pathways.

Foods are known to alter the epigenetics of rats on different diets.Some food components epigenetically increase the levels of DNA repair enzymes such as MGMT and MLH1and p53.Other food components can reduce DNA damage, such as soy isoflavones. In one study, markers for oxidative stress, such as modified nucleotides that can result from DNA damage, were decreased by a 3-week diet supplemented with soy. A decrease in oxidative DNA damage was also observed 2 h after consumption of anthocyanin-rich bilberry (Vaccinium myrtillius L.) pomace extract.

Techniques used to study epigenetics

Epigenetic research uses a wide range of molecular biological techniques to further understanding of epigenetic phenomena, including chromatin immunoprecipitation (together with its large-scale variants ChIP-on-chip and ChIP-Seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase identification (DamID) and bisulfite sequencing. Furthermore, the use of bioinformatics methods has a role in computational epigenetics.

Aneuploidy is the presence of an aberrant number of chromosomes in a cell, such as 45 or 47 instead of the usual 46 in a human cell. A difference of one or more entire sets of chromosomes is not included. A euploid cell is one that has any number of full chromosomal sets.

Some genetic abnormalities are caused by an extra or missing chromosome. Atypical chromosomal counts can also be found in cancer cells. Aneuploid solid tumours account for roughly 68 percent of all human tumours. When the chromosomes do not separate properly between the two cells during cell division, aneuploidy occurs (nondisjunction). The majority of cases of autosomal aneuploidy result in miscarriage.

Mechanisms

Aneuploidy arises from errors in chromosome segregation, which can go wrong in several ways.

Nondisjunction usually occurs as the result of a weakened mitotic checkpoint, as these checkpoints tend to arrest or delay cell division until all components of the cell are ready to enter the next phase. For example, if a checkpoint is weakened, the cell may fail to ‘notice’ that a chromosome pair is not lined with the spindle apparatus. In such a case, most chromosomes would separate normally (with one chromatid ending up in each cell), while others could fail to separate at all. This would generate a daughter cell lacking a copy and a daughter cell with an extra copy.

Completely inactive mitotic checkpoints may cause nondisjunction at multiple chromosomes, possibly all. Such a scenario could result in each daughter cell possessing a disjoint set of genetic material.

Merotelic attachment occurs when one kinetochore is attached to both mitotic spindle poles. One daughter cell would have a normal complement of chromosomes; the second would lack one. A third daughter cell may end up with the ‘missing’ chromosome.

Multipolar spindles: more than two spindle poles form. Such a mitotic division would result in one daughter cell for each spindle pole; each cell may possess an unpredictable complement of chromosomes.

Monopolar spindle: only a single spindle pole forms. This produces a single daughter cell with its copy number doubled.

A tetraploid intermediate may be produced as the end-result of the monopolar spindle mechanism. In such a case, the cell has double the copy number of a normal cell, and produces double the number of spindle poles as well. This results in four daughter cells with an unpredictable complement of chromosomes, but in the normal copy number.

Somatic mosaicism in the nervous system

Mosaicism for aneuploid chromosome content may be part of the constitutional make-up of the mammalian brain. In the normal human brain, brain samples from six individuals ranging from 2–86 years of age had mosaicism for chromosome 21 aneuploidy (average of 4% of neurons analyzed).This low-level aneuploidy appears to arise from chromosomal segregation defects during cell division in neuronal precursor cells,and neurons containing such aneuploid chromosome content reportedly integrate into normal circuits.However, recent research using single-cell sequencing has challenged these findings, and has suggested that aneuploidy in the brain is actually very rare.

Partial aneuploidy

The terms “partial monosomy” and “partial trisomy” are used to describe an imbalance of genetic material caused by loss or gain of part of a chromosome. In particular, these terms would be used in the situation of an unbalanced translocation, where an individual carries a derivative chromosome formed through the breakage and fusion of two different chromosomes. In this situation, the individual would have three copies of part of one chromosome (two normal copies and the portion that exists on the derivative chromosome) and only one copy of part of the other chromosome involved in the derivative chromosome. Robertsonian translocations, for example, account for a very small minority of Down syndrome cases (<5%). The formation of one isochromosome results in partial trisomy of the genes present in the isochromosome and partial monosomy of the genes in the lost arm.

Genome instability (also known as genetic instability or genomic instability) is characterised by a high frequency of mutations in a biological lineage’s genome. Changes in nucleic acid sequences, chromosomal rearrangements, and aneuploidy are all examples of mutations. In bacteria, genome instability does occur. Genome instability is a key element in carcinogenesis in multicellular species, and it’s also a role in several neurological illnesses including amyotrophic lateral sclerosis and myotonic dystrophy in humans.

DNA Replication Defects

In the cell cycle, DNA is usually most vulnerable during replication. The replisome must be able to navigate obstacles such as tightly wound chromatin with bound proteins, single and double stranded breaks which can lead to the stalling of the replication fork. Each protein or enzyme in the replisome must perform its function well to result in a perfect copy of DNA. Mutations of proteins such as DNA polymerase, ligase, can lead to impairment of replication and lead to spontaneous chromosomal exchanges. Proteins such as Tel1, Mec1 (ATR, ATM in humans) can detect single and double-stranded breaks and recruit factors such as Rmr3 helicase to stabilize the replication fork in order to prevent its collapse. Mutations in Tel1, Mec1, and Rmr3 helicase result in a significant increase of chromosomal recombination. ATR responds specifically to stalled replication forks and single-stranded breaks resulting from UV damage while ATM responds directly to double-stranded breaks. These proteins also prevent progression into mitosis by inhibiting the firing of late replication origins until the DNA breaks are fixed by phosphorylating CHK1, CHK2 which results in a signaling cascade arresting the cell in S-phase. For single stranded breaks, replication occurs until the location of the break, then the other strand is nicked to form a double stranded break, which can then be repaired by Break Induced Replication or homologous recombination using the sister chromatid as an error-free template. In addition to S-phase checkpoints, G1 and G2 checkpoints exist to check for transient DNA damage which could be caused by mutagens such as UV damage. An example is the Saccharomyces pombe gene rad9 which arrests the cells in late S/G2 phase in the presence of DNA damage caused by radiation. The yeast cells with defective rad9 failed to arrest following radiation, continued cell division and died rapidly while the cells with wild-type rad9 successfully arrested in late S/G2 phase and remained viable. The cells that arrested were able to survive due to the increased time in S/G2 phase allowing for DNA repair enzymes to function fully.

Fragile Sites

There are hotspots in the genome where DNA sequences are prone to gaps and breaks after inhibition of DNA synthesis such as in the aforementioned checkpoint arrest. These sites are called fragile sites, and can occur commonly as naturally present in most mammalian genomes or occur rarely as a result of mutations, such as DNA-repeat expansion. Rare fragile sites can lead to genetic disease such as fragile X mental retardation syndrome, myotonic dystrophy, Friedrich’s ataxia, and Huntington’s disease, most of which are caused by expansion of repeats at the DNA, RNA, or protein level. Although, seemingly harmful, these common fragile sites are conserved all the way to yeast and bacteria. These ubiquitous sites are characterized by trinucleotide repeats, most commonly CGG, CAG, GAA, and GCN. These trinucleotide repeats can form into hairpins, leading to difficulty of replication. Under replication stress, such as defective machinery or further DNA damage, DNA breaks and gaps can form at these fragile sites. Using a sister chromatid as repair is not a fool-proof backup as the surrounding DNA information of the n and n+1 repeat is virtually the same, leading to copy number variation. For example, the 16th copy of CGG might be mapped to the 13th copy of CGG in the sister chromatid since the surrounding DNA is both CGGCGGCGG…, leading to 3 extra copies of CGG in the final DNA sequence.

Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include amyloidosis.

The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, and certain chemicals. Multiple myeloma may develop from monoclonal gammopathy of undetermined significance that progresses to smoldering myeloma. The abnormal plasma cells produce abnormal antibodies, which can cause kidney problems and overly thick blood. The plasma cells can also form a mass in the bone marrow or soft tissue. When one tumor is present, it is called a plasmacytoma; more than one is called multiple myeloma. Multiple myeloma is diagnosed based on blood or urine tests finding abnormal antibodies, bone marrow biopsy finding cancerous plasma cells, and medical imaging finding bone lesions. Another common finding is high blood calcium levels.

Multiple myeloma is considered treatable, but generally incurable. Remissions may be brought about with steroids, chemotherapy, targeted therapy, and stem cell transplant. Bisphosphonates and radiation therapy are sometimes used to reduce pain from bone lesions.

Globally, multiple myeloma affected 488,000 people and resulted in 101,100 deaths in 2015.In the United States, it develops in 6.5 per 100,000 people per year and 0.7% of people are affected at some point in their lives. It usually occurs around the age of 60 and is more common in men than women.It is uncommon before the age of 40. Without treatment, the median survival in the prechemotherapy era was about 7 months. After the introduction of chemotherapy, prognosis improved significantly with a median survival of 24 to 30 months and a 10-year survival rate of 3%. Even further improvements in prognosis have occurred because of the introduction of newer biologic therapies and better salvage options, with median survivals now exceeding 60 to 90 months. With current treatments, survival is usually 4–5 years. The five-year survival rate is about 54%. The word myeloma is from the Greek myelo- meaning “marrow” and -oma meaning “tumor”.

Risk factors

• Monoclonal gammopathy of undetermined significance (MGUS) increases the risk of developing multiple myeloma. MGUS transforms to multiple myeloma at the rate of 1% to 2% per year, and almost all cases of multiple myeloma are preceded by MGUS.
• Smoldering multiple myeloma increases the risk of developing multiple myeloma. Individuals diagnosed with this premalignant disorder develop multiple myeloma at a rate of 10% per year for the first 5 years, 3% per year for the next 5 years, and then 1% per year.
• Obesity is related to multiple myeloma with each increase of body mass index by five increasing the risk by 11%.

Studies have reported a familial predisposition to myeloma. Hyperphosphorylation of a number of proteins—the paratarg proteins—a tendency that is inherited in an autosomal dominant manner, appears a common mechanism in these families. This tendency is more common in African-American with myeloma and may contribute to the higher rates of myeloma in this group.

Plasma cells, also known as plasma B cells, are white blood cells that are produced by B lymphocytes in the lymphoid organs and express huge amounts of proteins called antibodies in response to certain substances called antigens. These antibodies are delivered from plasma cells to the target antigen (foreign substance) through blood plasma and the lymphatic system, where they begin neutralisation or destruction. B cells differentiate into plasma cells, which produce antibody molecules that are very similar to the precursor B cell’s receptors.

Structure

Plasma cells are large lymphocytes with abundant cytoplasm and a characteristic appearance on light microscopy. They have basophilic cytoplasm and an eccentric nucleus with heterochromatin in a characteristic cartwheel or clock face arrangement. Their cytoplasm also contains a pale zone that on electron microscopy contains an extensive Golgi apparatus and centrioles (EM picture). Abundant rough endoplasmic reticulum combined with a well-developed Golgi apparatus makes plasma cells well-suited for secreting immunoglobulins. Other organelles in a plasma cell include ribosomes, lysosomes, mitochondria, and the plasma membrane.

Surface antigens

Terminally differentiated plasma cells express relatively few surface antigens, and do not express common pan-B cell markers, such as CD19 and CD20. Instead, plasma cells are identified through flow cytometry by their additional expression of CD138, CD78, and the Interleukin-6 receptor. In humans, CD27 is a good marker for plasma cells; naïve B cells are CD27-, memory B-cells are CD27+ and plasma cells are CD27++.

The surface antigen CD138 (syndecan-1) is expressed at high levels.

Another important surface antigen is CD319 (SLAMF7). This antigen is expressed at high levels on normal human plasma cells. It is also expressed on malignant plasma cells in multiple myeloma. Compared with CD138, which disappears rapidly ex vivo, the expression of CD319 is considerably more stable.

Development

After leaving the bone marrow, the B cell acts as an antigen-presenting cell (APC) and internalizes offending antigens, which are taken up by the B cell through receptor-mediated endocytosis and processed. Pieces of the antigen (which are now known as antigenic peptides) are loaded onto MHC II molecules, and presented on its extracellular surface to CD4+ T cells (sometimes called T helper cells). These T cells bind to the MHC II-antigen molecule and cause activation of the B cell. This is a type of safeguard to the system, similar to a two-factor authentication method. First, the B cells must encounter a foreign antigen and are then required to be activated by T helper cells before they differentiate into specific cells.

Upon stimulation by a T cell, which usually occurs in germinal centers of secondary lymphoid organs such as the spleen and lymph nodes, the activated B cell begins to differentiate into more specialized cells. Germinal center B cells may differentiate into memory B cells or plasma cells. Most of these B cells will become plasmablasts (or “immature plasma cells”), and eventually plasma cells, and begin producing large volumes of antibodies. Some B cells will undergo a process known as affinity maturation.This process favors, by selection for the ability to bind antigen with higher affinity, the activation and growth of B cell clones able to secrete antibodies of higher affinity for the antigen.

Immature plasma cells[edit]

The most immature blood cell that is considered of plasma cell lineage is the plasmablast. Plasmablasts secrete more antibodies than B cells, but less than plasma cells. They divide rapidly and are still capable of internalizing antigens and presenting them to T cells. A cell may stay in this state for several days, and then either die or irrevocably differentiate into a mature, fully differentiated plasma cell. Differentiation of mature B cells into plasma cells is dependent upon the transcription factors Blimp-1/PRDM1 and IRF4

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules; however, these antibodies are not secreted. Rather, they are inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. Additionally, B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines. In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the ‘B’ stands for bursa and not bone marrow as commonly believed.

B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response.

Antigen presentation is the process of a cell displaying antigen bound by major histocompatibility complex (MHC) proteins on its surface; this is known as antigen presentation. These complexes may be recognised by T cells via their T cell receptors (TCRs). Antigens are processed by APCs and presented to T-cells.

Antigens can be presented in a variety of ways by almost all cell types. They can be found in a wide range of tissues. Professional antigen-presenting cells, such as macrophages, B cells, and dendritic cells, present external antigens to helper T cells, whereas virus-infected cells (or cancer cells) can present cytotoxic T cells with antigens produced inside the cell.

Activation

B cell activation: from immature B cell to plasma cell or memory B cell

B cell activation occurs in the secondary lymphoid organs (SLOs), such as the spleen and lymph nodes. After B cells mature in the bone marrow, they migrate through the blood to SLOs, which receive a constant supply of antigen through circulating lymph. At the SLO, B cell activation begins when the B cell binds to an antigen via its BCR. Although the events taking place immediately after activation have yet to be completely determined, it is believed that B cells are activated in accordance with the kinetic segregation mode, initially determined in T lymphocytes. This model denotes that before antigen stimulation, receptors diffuse through the membrane coming into contact with Lck and CD45 in equal frequency, rendering a net equilibrium of phosphorylation and non-phosphorylation. It is only when the cell comes in contact with an antigen presenting cell that the larger CD45 is displaced due to the close distance between the two membranes. This allows for net phosphorylation of the BCR and the initiation of the signal transduction pathway. Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells and B1 B cells preferentially undergo T cell-independent activation.

B cell activation is enhanced through the activity of CD21, a surface receptor in complex with surface proteins CD19 and CD81 (all three are collectively known as the B cell coreceptor complex). When a BCR binds an antigen tagged with a fragment of the C3 complement protein, CD21 binds the C3 fragment, co-ligates with the bound BCR, and signals are transduced through CD19 and CD81 to lower the activation threshold of the cell.

Antigen presentation is the process of a cell displaying antigen bound by major histocompatibility complex (MHC) proteins on its surface; this is known as antigen presentation. These complexes may be recognised by T cells via their T cell receptors (TCRs). Antigens are processed by APCs and presented to T-cells.

Antigens can be presented in a variety of ways by almost all cell types. They can be found in a wide range of tissues. Professional antigen-presenting cells, such as macrophages, B cells, and dendritic cells, present external antigens to helper T cells, whereas virus-infected cells (or cancer cells) can present cytotoxic T cells with antigens produced inside the cell.

Types and functions

Antigen-presenting cells fall into two categories: professional and non-professional. Those that express MHC class II molecules along with co-stimulatory molecules and pattern recognition receptors are often called professional antigen-presenting cells. The non-professional APCs express MHC class I molecules.

T cells must be activated before they can divide and perform their function. This is achieved by interacting with a professional APC which presents an antigen recognized by their T cell receptor. The APC involved in activating T cells is usually a dendritic cell. T cells cannot recognize (and therefore cannot respond to) “free” or soluble antigens. They can only recognize and respond to antigen that has been processed and presented by cells via carrier molecules like MHC molecules. Helper T cells can recognize exogenous antigen presented on MHC class II; cytotoxic T cells can recognize endogenous antigen presented on MHC class I. Most cells in the body can present antigen to CD8+ cytotoxic T cells via MHC class I; however, the term “antigen-presenting cell” is often used specifically to describe professional APCs. Such cells express MHC class I and MHC class II molecules and can stimulate CD4+ helper T cells as well as cytotoxic T cells.^[2][3]

APCs can also present foreign and self lipids to T cells and NK cells by using the CD1 family of proteins, which are structurally similar to the MHC class I family.

Professional APCs

Professional APCs specialize in presenting antigens to T cells. They are very efficient at internalizing antigens, either by phagocytosis (e.g. macrophages), or by receptor-mediated endocytosis (B cells), processing the antigen into peptide fragments and then displaying those peptides (bound to a class II MHC molecule) on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading to activation of the T cell. The expression of co-stimulatory molecules and MHC class II are defining features of professional APCs. All professional APCs also express MHC class I molecules as well.

The main types of professional antigen-presenting cells are dendritic cells, macrophages and B cells.

Dendritic cells (DCs)

Dendritic cells have the broadest range of antigen presentation and are necessary for activation of naive T cells. DCs present antigen to both helper and cytotoxic T cells. They can also perform cross-presentation, a process by which they present exogenous antigen on MHC class I molecules to cytotoxic T cells. Cross-presentation allows for the activation of these T cells. Dendritic cells also play a role in peripheral tolerance, which contributes to prevention of auto-immune disease.

Prior to encountering foreign antigen, dendritic cells express very low levels of MHC class II and co-stimulatory molecules on their cell surface. These immature dendritic cells are ineffective at presenting antigen to T helper cells. Once a dendritic cell’s pattern-recognition receptors recognize a pathogen-associated molecular pattern, antigen is phagocytosed and the dendritic cell becomes activated, upregulating the expression of MHC class II molecules. It also upregulates several co-stimulatory molecules required for T cell activation, including CD40 and B7. The latter can interact with CD28 on the surface of a CD4+ T cell. The dendritic cell is then a fully mature professional APC. It moves from the tissue to lymph nodes, where it encounters and activates T cells.