**6. Function of epithelial reticular cells**

Epithelial reticular cells, also called as TECs, are present both in the cortex and medulla; however, it can be easily recognizable in the thymic medulla through histology. These cells contained the thymic granules which is assumed to be the called as the thymic hormone [12]. This structure has the following functions;


The pluripotent progenitor cells migrated from the bone marrow to the thymus parenchyma, where the maturation of the unexperienced T cells occurs in the complex microarchitecture. However, this structure changes with the age.

### **7. Age associated changes occurs in the thymus**

Aging is an irreversible, on-going, and inevitable progression that is correlated through manifold organ dysfunction. The key organ of immune system and

**27**

being replaced by the stromal cells.

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

primary organ of T cell production is the thymus gland which is endodermal in nature. Involution of the thymus with progressing age is into the consequences of a decreased T cell production primarily and leads toward a long list of the following diseases and even a mortality of the individual [6]. The corticomedullary junction is disrupted and the number of medullary epithelial cells are also decrease. This age-related cellular apoptosis and atrophy is still un-answered. There are several reasons to be considered for this process, but the main cause known is reactive oxygen species (ROS). The entity that are assumed to be responsible for expressing the age-related changes in the thymus is due to the discrepancy amongst the free oxygen-derived radicles and that of the antioxidants. Mitochondria is the main site were such reactive species are produced. Inside mitochondria, the oxidative stress produce ROS which results into mitochondrial damage within the cells and leads to liberate more ROS. In fact, aging is a physiological multifactorial process accompanied by decline of organ function. Histologically, the thymus gland of mammals divided into three consecutive morphological stages; the epithelial, the lymphopoietic, and the differentiated cellular microenvironment [7]. The progenitor cells are synthesizing in the thymus which later differentiated into mature T cells. Thymus also comprises the main stromal niche termed as thymic epithelial space. It supports T cell development and maturation [6]. The thymus is greater in size and is very dynamic in the neonates and pre-adolescents. With the progression in age, the involution starts and ultimately disappears and are then replaced by rudiments and fat. The process of involution started just after 1 year of birth [2]. If in case the thymus is absent in individual congenitally, then there would be a probable chance of deficiency of T cells. The main components of the thymus which undergoes involution during the aging include the T cells of hematopoietic origin and the TECs of non-hematopoietic origin. During the process of involution, disruption of the thymic epithelial/endothelial ratio happened and results into gradual loss of pro-T cells. Primarily just after the start of involution, the thymic epithelium mass is decreased in the parenchyma. This decrease in epithelium leads toward the disorganization of corticomedullary junction and results into loss of demarcation between the thymic cortex and medulla. This process where a continuous loss of cells and their functions is called aging [6]. Histology of thymus gland varies with the individual's age. It is observed that this gland is extremely delicate to stand against the biological abnormalities, for example, autoimmune diseases, infection, and age progression. It attains its maximum development shortly after birth. After attaining the age of puberty, the thymus gland regress and degenerate. Due to this effect the lymphocyte production decreases and the reticuloepithelial cells (thymic corpuscles) increases. Cellular portion, especially of T cell of thymus gland, decreases and are being replaced by connective tissue and adipose cells. Parenchyma of the thymus gland at and after puberty is filled with adipose tissue. Immunity, however, in this stage it is not compromised because progeny of the T lymphocytes has already been established. Thymus gland is well developed only in late fetal life and persists for a few months after birth [6]. Subsequent to this period, it undergoes rapid atrophy, fatty infiltration, and the amyloid degeneration [13]. Increase in the amount of adipose tissue and fat-bearing cells in the thymus parenchyma indicates that the body is now vulnerable to the infection and autoimmune diseases. So, in adult, only a thin remnant appeared in the anterior mediastinum or has entirely disappeared. Thymus gland size is also affected by the sex-steroid hormone and hypothalamic-pituitary-adrenal axes hormones [14]. It has been found that during the thymus involution, the CT which is present in the capsule, septa, perivascular tissue, and in the stroma of the cortex and medulla is getting enriched with the fibronectin contents. Later, most of the thymic parenchymal areas are

*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*

primary organ of T cell production is the thymus gland which is endodermal in nature. Involution of the thymus with progressing age is into the consequences of a decreased T cell production primarily and leads toward a long list of the following diseases and even a mortality of the individual [6]. The corticomedullary junction is disrupted and the number of medullary epithelial cells are also decrease. This age-related cellular apoptosis and atrophy is still un-answered. There are several reasons to be considered for this process, but the main cause known is reactive oxygen species (ROS). The entity that are assumed to be responsible for expressing the age-related changes in the thymus is due to the discrepancy amongst the free oxygen-derived radicles and that of the antioxidants. Mitochondria is the main site were such reactive species are produced. Inside mitochondria, the oxidative stress produce ROS which results into mitochondrial damage within the cells and leads to liberate more ROS. In fact, aging is a physiological multifactorial process accompanied by decline of organ function. Histologically, the thymus gland of mammals divided into three consecutive morphological stages; the epithelial, the lymphopoietic, and the differentiated cellular microenvironment [7]. The progenitor cells are synthesizing in the thymus which later differentiated into mature T cells. Thymus also comprises the main stromal niche termed as thymic epithelial space. It supports T cell development and maturation [6]. The thymus is greater in size and is very dynamic in the neonates and pre-adolescents. With the progression in age, the involution starts and ultimately disappears and are then replaced by rudiments and fat. The process of involution started just after 1 year of birth [2]. If in case the thymus is absent in individual congenitally, then there would be a probable chance of deficiency of T cells. The main components of the thymus which undergoes involution during the aging include the T cells of hematopoietic origin and the TECs of non-hematopoietic origin. During the process of involution, disruption of the thymic epithelial/endothelial ratio happened and results into gradual loss of pro-T cells. Primarily just after the start of involution, the thymic epithelium mass is decreased in the parenchyma. This decrease in epithelium leads toward the disorganization of corticomedullary junction and results into loss of demarcation between the thymic cortex and medulla. This process where a continuous loss of cells and their functions is called aging [6]. Histology of thymus gland varies with the individual's age. It is observed that this gland is extremely delicate to stand against the biological abnormalities, for example, autoimmune diseases, infection, and age progression. It attains its maximum development shortly after birth. After attaining the age of puberty, the thymus gland regress and degenerate. Due to this effect the lymphocyte production decreases and the reticuloepithelial cells (thymic corpuscles) increases. Cellular portion, especially of T cell of thymus gland, decreases and are being replaced by connective tissue and adipose cells. Parenchyma of the thymus gland at and after puberty is filled with adipose tissue. Immunity, however, in this stage it is not compromised because progeny of the T lymphocytes has already been established. Thymus gland is well developed only in late fetal life and persists for a few months after birth [6]. Subsequent to this period, it undergoes rapid atrophy, fatty infiltration, and the amyloid degeneration [13]. Increase in the amount of adipose tissue and fat-bearing cells in the thymus parenchyma indicates that the body is now vulnerable to the infection and autoimmune diseases. So, in adult, only a thin remnant appeared in the anterior mediastinum or has entirely disappeared. Thymus gland size is also affected by the sex-steroid hormone and hypothalamic-pituitary-adrenal axes hormones [14]. It has been found that during the thymus involution, the CT which is present in the capsule, septa, perivascular tissue, and in the stroma of the cortex and medulla is getting enriched with the fibronectin contents. Later, most of the thymic parenchymal areas are being replaced by the stromal cells.

*Thymus*

**4. Blood-thymus barrier**

**5. Maturation and selection of T cells**

**6. Function of epithelial reticular cells**

• It formed the blood-thymus barrier.

tor, interleukin, and interferon are secreted.

**7. Age associated changes occurs in the thymus**

It is a physical barrier formed by endothelial cells, epithelial reticular cells, and macrophages. Its function is to prevent developing lymphocytes from the exposure of blood borne antigen [8]. This barrier provides tremendous environment for the substance exchange between vasculature and the thymus also help maturation of the immature thymocytes. Macrophages present outside the capillaries prevent the interaction of the substances that are transported in the blood vessels with the developing T cells in the cortex. Matured T cells leave the thymus gland through the blood vessels and colonize in the lymph node, spleen, and lymphatic tissue of the organism [11].

Maturation is the condition of developing progenitor within the thymus parenchyma, where the cells known as thymocytes, undergoes various developmental processes to perform exclusively. These cells can be recognized based on manifestation of various markers on the cell surface and the antigen presenting cells present the T cells with self and foreign antigen [11]. It usually consists of positive selection in which the lymphocytes that recognize the foreign antigens survived and reached to the maturity then enter the medulla through the cortex. Later, goes to the other sites in the body via blood [9]. Maturation is a very complicated process and only a small number of lymphocytes reach to the stage of maturity in the thymus. The negative selection in which the lymphocytes which are incapable to distinguish the self-antigens are eliminated by the macrophages. This is approximately 95% of the total cells.

Epithelial reticular cells, also called as TECs, are present both in the cortex and medulla; however, it can be easily recognizable in the thymic medulla through histology. These cells contained the thymic granules which is assumed to be the called

• Secrete hormone which are required for proliferation, differentiation, and maturation of T cells. Also, for the expression of their surface markers. The hormones including thymulin, thymopoietin, thymosin, thymic numeral fac-

• It forms thymic (Hassall's) corpuscles, distinctive whorls, in the medulla of the thymus gland. The thymus gland is identified by this thymic corpuscle.

The pluripotent progenitor cells migrated from the bone marrow to the thymus

Aging is an irreversible, on-going, and inevitable progression that is correlated

parenchyma, where the maturation of the unexperienced T cells occurs in the complex microarchitecture. However, this structure changes with the age.

through manifold organ dysfunction. The key organ of immune system and

as the thymic hormone [12]. This structure has the following functions;

**26**
