**10. Means to modulate the functioning of the thymus gland**

Thymic involution with age has negative impacts on the immune system. Proper performance of the thymus and integral immune system are required to protect against disorders. With the advancements of the modern sciences, a technique named as photobiomodulation is newly employed to slower the process of thymic involution. This delayed process improves immunity and may add in extension of the individual lifespan. Another new method which reduce the thymus atrophy and boost the thymus functioning is the sex-steroid ablation therapies [14]. Genetics has also an important role for determining the initial thymus size and rate of involution. Many hormonal medications, surgical procedures, and applications of antioxidants are testified as replacements for the reversal of aging in atrophy of the thymus. Males display a trend of lower grade thymopoiesis in comparison to females. There are several procedures that can improve the normal physiology of the thymus gland which ultimately leads to strengthen the immune system active for prolong time [20]. Continuous use of dietary supplements like rosehips, echinacea, olive leaf, and cruciferous vegetables are tested to be connected to establishment of the thymus health. These supplements are comprised of glucosinolates. This substance is famous for fighting contrary to the tumorous cells and other malformations in the tissues. Vegetables especially cruciferous vegetables like cauliflower, Bok Choy, broccoli, and cabbage are good source of nutrients that trigger antioxidants and anti-inflammatory responses. This can also assist thymus function. Proper timely intake of antioxidants and various vitamins like E and C in the diet is mostly necessary. These are needed for proper functioning of the thymus cells [21]. Zinc is also a very useful micronutrient required for the growth and growth of the vertebrate. The immune system is very sensitive to zinc deficiency and produces the multiple disturbances like atrophy of the thymus parenchyma and the increased chances for a disease to occur [22]. Many genes which regulate thymus gland activity are under the response of metalloenzymes in which zinc act as metal. So, dietary supplementation is very necessary for the proper functioning of the thymus gland otherwise, there may be a serious consequence related to the synthesis of the T lymphocytes. Exercise on daily basis is additional tool to ensure blood circulation throughout the body and the thymus gland. In this way increased blood flow will ensure that thymus waste products are removed promptly and do not cause damage to the thymus. Furthermore, through the circulation the key nutrients reach around the body more rapidly which allow quicker recovery to take place. Thymus gland stimulate the production of white blood cells that help against infection by thymosin hormone. This thymus glandular extract regulates many other immune functions. The extract called as thymomodulin, obtained from bovine species and act as immune boosting activities in immunodeficient individuals. Such extract act as a substitute and work against respiratory

**31**

*Microarchitecture of the Thymus Gland; Its Age and Disease-Associated Morphological…*

the probiotics are the *Bifidobacteria*, *Streptococci*, *Lactobacilli*, *Enterococcus*,

*Pediococcus*, along with some yeast. Some probiotics like *L. paracasei* CNCM I-1518 and *L. casei* CRL 431 have a toll like receptors through which they make an attachment with the intestinal epithelial cells. Here, they mediate the immune stimulation by producing cytokines such as IL-6 and protein 1, which is chemoattractant in nature. Most of the probiotics are physically strengthening the intestinal barrier by producing the mucus layer, which is secreted from the goblet cells in the intestine. This viscous and impermeable mucus layers protect the intestinal barrier also stimulate the IgA and motivate the immunity. The probiotics also improve the health of animal by producing low molecular organic acids such as acetic acid and lactic acid. They also produce high molecular weight antimicrobial compound known as bacteriocins. These have strong inhibitory effect on the pathogenic gram-negative bacteria, i.e., *H. pylori* and the *Salmonella* species [24]. They inhibit the growth of pathogenic microbes and improve the health of animals. The lactobacilli containing probiotic has the ability to protect the children and adults from antibiotic-associated diarrhea and reduces its risk. *L. acidophilus* or *L. casei* are those probiotics can regulate the composition of microbial species present in the gut at balance level and suppress the growth of pathogenic bacteria. *L. acidophilus* or *L. casei* and lactic acid bacteria together act and result into suppressing the fecal coliform and other anaerobic bacteria. Some probiotics are also responsible for the shifting of microbes of gut to the beneficial bacteria, e.g., *Prevotella* and *Oscillibacter*. These bacteria are responsible for the production of anti-inflammatory metabolites. It can cause decrease the polarization of Th17 which favors the differentiation of anti-inflammatory Treg/ Type 1 regulatory T (Tr1) cells in the gut. The *S. thermophilus* and *L. acidophilus*

infections and many other infections like asthma, food allergies and hay fever. Olive leaf extract has a significant effect on thymocyte apoptosis and cell cycle progression to protect the thymus gland from toxicity. Tapping sternum is a practice which may also stimulate thymus gland. But this practice is a bit laborious. Organic acid has a positive effect on the immune system. It has been reported that sodium butyrate improves the thymus histology and ultimately improves the immune system of a body [23]. Probiotics are called as the group of beneficial bacteria. Probiotics are generally defined as the friendly living micro-organ¬isms, when taken orally in an appropriate dose, exhibit a beneficial effect on the host health. When the probiotics is taken orally, they go along side of the lumen of the gastrointestinal tract and interact with the mucosal immune system. Here, the whole bacteria or its cell wall mediate a network of signal production and activate the immune system. They produce different kinds of cytokines and chemokines and result into the activation of T lymphocytes. Another model of mechanism of action of probiotics is that they can suppress the growth of pathogenic bacteria and help in the balancing of microflora environment in the gastrointestinal tract. Probiotics protect the body against the pathogens by the induction of direct killing, nutritional competency of pathogens, and meanwhile by triggering the gut-associated immune repertoire. Thymus gland is known as the "Master gland of immunity" [2]. It regulates the immune system by producing different types of chemical known as cytokines that enhance the migration of T lymphocytes and meantime enhances the immunity [20]. The probiotic fermented milk (PFM) is a nutritional supplement which is used to improve the histology of the thymus gland mean to say it will cause a decrease in cellular apoptosis and enhance the percentage of CD4/CD8 cells. The PFM enhance the production of different kinds of cytokines in the thymus gland. This type of milk is usually used in case of protein-energy malnutrition; which result into malfunctioning of the immune system. This milk or bacterial-free supernatant helps to improve the immune system by activating thymus gland activity. Commonly used probiotics are specific strains of the lactic acid bacteria. The main genus includes in

*DOI: http://dx.doi.org/10.5772/intechopen.88480*

#### *Microarchitecture of the Thymus Gland; Its Age and Disease-Associated Morphological… DOI: http://dx.doi.org/10.5772/intechopen.88480*

infections and many other infections like asthma, food allergies and hay fever. Olive leaf extract has a significant effect on thymocyte apoptosis and cell cycle progression to protect the thymus gland from toxicity. Tapping sternum is a practice which may also stimulate thymus gland. But this practice is a bit laborious. Organic acid has a positive effect on the immune system. It has been reported that sodium butyrate improves the thymus histology and ultimately improves the immune system of a body [23]. Probiotics are called as the group of beneficial bacteria. Probiotics are generally defined as the friendly living micro-organ¬isms, when taken orally in an appropriate dose, exhibit a beneficial effect on the host health. When the probiotics is taken orally, they go along side of the lumen of the gastrointestinal tract and interact with the mucosal immune system. Here, the whole bacteria or its cell wall mediate a network of signal production and activate the immune system. They produce different kinds of cytokines and chemokines and result into the activation of T lymphocytes. Another model of mechanism of action of probiotics is that they can suppress the growth of pathogenic bacteria and help in the balancing of microflora environment in the gastrointestinal tract. Probiotics protect the body against the pathogens by the induction of direct killing, nutritional competency of pathogens, and meanwhile by triggering the gut-associated immune repertoire. Thymus gland is known as the "Master gland of immunity" [2]. It regulates the immune system by producing different types of chemical known as cytokines that enhance the migration of T lymphocytes and meantime enhances the immunity [20]. The probiotic fermented milk (PFM) is a nutritional supplement which is used to improve the histology of the thymus gland mean to say it will cause a decrease in cellular apoptosis and enhance the percentage of CD4/CD8 cells. The PFM enhance the production of different kinds of cytokines in the thymus gland. This type of milk is usually used in case of protein-energy malnutrition; which result into malfunctioning of the immune system. This milk or bacterial-free supernatant helps to improve the immune system by activating thymus gland activity. Commonly used probiotics are specific strains of the lactic acid bacteria. The main genus includes in the probiotics are the *Bifidobacteria*, *Streptococci*, *Lactobacilli*, *Enterococcus*, *Pediococcus*, along with some yeast. Some probiotics like *L. paracasei* CNCM I-1518 and *L. casei* CRL 431 have a toll like receptors through which they make an attachment with the intestinal epithelial cells. Here, they mediate the immune stimulation by producing cytokines such as IL-6 and protein 1, which is chemoattractant in nature. Most of the probiotics are physically strengthening the intestinal barrier by producing the mucus layer, which is secreted from the goblet cells in the intestine. This viscous and impermeable mucus layers protect the intestinal barrier also stimulate the IgA and motivate the immunity. The probiotics also improve the health of animal by producing low molecular organic acids such as acetic acid and lactic acid. They also produce high molecular weight antimicrobial compound known as bacteriocins. These have strong inhibitory effect on the pathogenic gram-negative bacteria, i.e., *H. pylori* and the *Salmonella* species [24]. They inhibit the growth of pathogenic microbes and improve the health of animals. The lactobacilli containing probiotic has the ability to protect the children and adults from antibiotic-associated diarrhea and reduces its risk. *L. acidophilus* or *L. casei* are those probiotics can regulate the composition of microbial species present in the gut at balance level and suppress the growth of pathogenic bacteria. *L. acidophilus* or *L. casei* and lactic acid bacteria together act and result into suppressing the fecal coliform and other anaerobic bacteria. Some probiotics are also responsible for the shifting of microbes of gut to the beneficial bacteria, e.g., *Prevotella* and *Oscillibacter*. These bacteria are responsible for the production of anti-inflammatory metabolites. It can cause decrease the polarization of Th17 which favors the differentiation of anti-inflammatory Treg/ Type 1 regulatory T (Tr1) cells in the gut. The *S. thermophilus* and *L. acidophilus*

*Thymus*

Thymic lymphomas are tumors which originate from the thymocytes of the thymus gland. These lymphomas or leukemia acts like the precursors of the origin of the thymocyte are often classified as T acute lymphoblastic leukemia/lymphoma. Before 1950, the radiation was used to cure the people who are suffering from the enlarged thymus gland particularly the children. The post-operative complication in the treated people includes an elevated incidence of thyroid cancer and leukemia. The rare malformation of thymus gland includes the cervical thymus cyst which is something confusing with the tumors. In the literature, there is no as such detail study of the thymic cyst prevalence. There is no such common lesion appeared which are present in this condition. In the childhood, there are more chances of the

Thymic involution with age has negative impacts on the immune system. Proper performance of the thymus and integral immune system are required to protect against disorders. With the advancements of the modern sciences, a technique named as photobiomodulation is newly employed to slower the process of thymic involution. This delayed process improves immunity and may add in extension of the individual lifespan. Another new method which reduce the thymus atrophy and boost the thymus functioning is the sex-steroid ablation therapies [14]. Genetics has also an important role for determining the initial thymus size and rate of involution. Many hormonal medications, surgical procedures, and applications of antioxidants are testified as replacements for the reversal of aging in atrophy of the thymus. Males display a trend of lower grade thymopoiesis in comparison to females. There are several procedures that can improve the normal physiology of the thymus gland which ultimately leads to strengthen the immune system active for prolong time [20]. Continuous use of dietary supplements like rosehips, echinacea, olive leaf, and cruciferous vegetables are tested to be connected to establishment of the thymus health. These supplements are comprised of glucosinolates. This substance is famous for fighting contrary to the tumorous cells and other malformations in the tissues. Vegetables especially cruciferous vegetables like cauliflower, Bok Choy, broccoli, and cabbage are good source of nutrients that trigger antioxidants and anti-inflammatory responses. This can also assist thymus function. Proper timely intake of antioxidants and various vitamins like E and C in the diet is mostly necessary. These are needed for proper functioning of the thymus cells [21]. Zinc is also a very useful micronutrient required for the growth and growth of the vertebrate. The immune system is very sensitive to zinc deficiency and produces the multiple disturbances like atrophy of the thymus parenchyma and the increased chances for a disease to occur [22]. Many genes which regulate thymus gland activity are under the response of metalloenzymes in which zinc act as metal. So, dietary supplementation is very necessary for the proper functioning of the thymus gland otherwise, there may be a serious consequence related to the synthesis of the T lymphocytes. Exercise on daily basis is additional tool to ensure blood circulation throughout the body and the thymus gland. In this way increased blood flow will ensure that thymus waste products are removed promptly and do not cause damage to the thymus. Furthermore, through the circulation the key nutrients reach around the body more rapidly which allow quicker recovery to take place. Thymus gland stimulate the production of white blood cells that help against infection by thymosin hormone. This thymus glandular extract regulates many other immune functions. The extract called as thymomodulin, obtained from bovine species and act as immune boosting activities in immunodeficient individuals. Such extract act as a substitute and work against respiratory

thymic cyst and the ectopic cervical thymus than the adults.

**10. Means to modulate the functioning of the thymus gland**

**30**

probiotics have ability to increase the intestinal integrity by enhancing the gene expression in tight junction signaling. These probiotics decrease the adhesion entero-invasive *E. coli* in HT29 and Caco-2 cells by the maintenance (actin and ZO-1) or enhancement (actinin and occludin) of cytoskeletal and tight junctional protein phosphorylation. Antimicrobial peptides produced by probiotics are now considered as the future of the new class of therapeutics because it produces lesser resistance and have a specific antimicrobial activity to protect the host. Different kinds of antimicrobial peptides like lysozyme, secretory phospholipase A2, defensins, defensin-like peptides (elafin and SLPI), and cathelicidins are produce from the paneth cells. These are the characteristics epithelial cells of the small intestinal which is located at the bottom of the intestinal crypts. The probiotics *B. subtilis* was found in improvement of the thymus microarchitecture in broilers [25]. Prebiotics are those high fibrous non-digestible food particles that are used as a source of energy for the beneficial bacteria like bifidobacteria and lactobacteria and symbiotic is the combination of the probiotics and the prebiotics. It modulates the host immune system and usually effect the intestinal microflora and regulate the immune system directly and indirectly. When symbiotic are administered during the embryo it enhances the proliferation of the lymphocytes by causing decrease in the cortex/medulla ratio of the thymus gland. In a research, a number of prebiotics like inulin (Pre1), Bi2tos (Pre2), and also a symbiotic composed of inulin and *Lactococcus lactis* subsp. lactis IBB SL1 (Syn1), a symbiotic composed of Bi2tos and *L. lactis* subsp. cremoris IBB SC1 (Syn2), is administrated in the early chick embryonic life in order to check its effect on the lymphoid tissue activity. B. longum and a prebiotic (Synergy 1) when administered into the body, can enhance the release of defensins from epithelial cells and they have antimicrobial activity. The outcomes of the research come in the form of enhance lymphocytes proliferation. When the Bi2tos were administered with *L. lactis* subsp. cremoris (Syn2) they caused reduction of the thymic cortex to medullary ratio [26]. This indicates the more spreading of the medulla without the effect on the cortex representing the subsequent impacts on the thymus.
