In the medulla, the stroma consists of prominent epithelial cells that have large, pale-staining nuclei and substantial amounts of eosinophilic (pink-staining) cytoplasm.  There are fewer T cells because most of them have entered the blood stream via vessels at the corticomedullary junction.  Antigen presenting cells (APC) are also found in the medulla (not labelled) where they are called thymic interdigitating cells. These cells are thought to present self-antigens to the matured T cells.  T cells that recognize these self-antigens are removed by a process called apotosis.  This process helps to prevent autoimmune diseases.

Micrographs of the thymus.  (Lab slide 220)

The parenchyma and stroma have different appearances depending on whether you are looking at the cortex or the medulla. 

  In the cortex, the parenchyma consists mostly of the developing T lymphocytes. It is here that the T cell receptor (TCR) genes are rearranged so that the mature T cells obtain their specific surface markers.  The stroma consists of sparse, delicate epithelial cells obscured by all of the lymphocytes. These epithelial cells form the support structure for the developing T cells but also play an important role in isolating the T cells from foreign anitgens during their development.

One prominent and identifying feature of the medulla is the presence of Hassall's corpuscles thought to represent degenerating epithelial cells.  These impressive structures begin to form in the fetus and increase in number and size as the animal ages. The arrows on the above micrograph indicate several epithelial cells that are part of a Hassall's corpuscle in the medulla of the thymus.

Structural basis for function of the thymus:

In fulfilling its major functions in producing immunocompetent but naïve T cells and in achieving immunological self-tolerance, the thymus has some special structural arrangements unlike those found in other organs.

• First, to keep the developing T lymphocytes "protected" so that they can develop their surface receptors in a "climate" that is not influenced by antigens, the thymic epithelial cells form a continuous layer along the inner surface of the capsule extending into the thymus along the septa and along blood vessels.  These cells actually provide a cellular framework for a space that is kept separate from other spaces such as the bloodstream.  This separation is maintained by desmosomes between adjacent epithelial cells and their close contact with endothelial cells of capillaries.  The "barrier" that results is called the blood-thymus barrier; it is similar in structure to the blood-brain barrier.  It is within this confined and protected space that the T lymphocytes develop into immunocompetent yet naïve T cells.  The integrity of the  space within the epithelial cell framework is extremely important because it prevents the premature stimulation of T cells by antigens. 
  
  Blood-thymus barrier - components
  
  - tight junctions between endothelial cells
  - basal lamina of endothelium
  - small connective tissue space
  - basal lamina of epithelial cell
  - continuous sheet of epithelial cell
  

• Second, to provide a mechanism by which the newly developed immunocompetent and naïve T cells can be added back to the circulation, the blood supply of the thymus also has some peculiarities.  Most arteries enter the thymus through the capsule, course via connective septae through the cortex down to the level of the corticomedullary junction where they then actually enter the parenchyma of the organ.  Capillaries from these arterial branches return to the region of the cortex within the parenchyma.  These capillaries are special in that they are not permeable to macromolecules, thus preventing any antigenic contact with developing T cells in the cortex. Postcapillary venules that derive from these same capillaries are permeable to macromolecules and lymphocytes.  The new immunocompetent T cells move into these postcapillary venules to eventually join the general circulation and move to the other tissues and organs that are part of the immune system.  Some capillaries from the arterial branches entering the thymus from the capsule extend down directly into the medulla to supply the tissue with oxygen and nutrients then reconvene as postcapillary venules that join the postcapillary venules coming from capillaries in the cortex.  Thus, blood draining the cortex and the medulla combine in the postcapillary venules and exit the thymus through typical venous pathways.

• Third, to ensure that self-tolerance is acheived, the medulla of the thymus has antigen presenting cells (APC) that are thought to present self-antigens to the matured T cells.  Any T cells that recognize these self-antigens are removed thus preventing development of autoimmune diseases.

Histological organization:

The cortex is composed of the cortical sinuses surrounded by dense accumulations of lymphocytes.  In the more superficial cortex the lymphocytes are arranged into spherical follicles, lymphoid follicles.  It is here that B lymphocytes are activated and undergo proliferation.  

Germinal Center (GC) -  contains pale-staining cells. The open, pale-staining nature of the nuclei of these cells indicate that they are B lymphocytes undergoing active proliferation. Other cells include:

• follicular dendritic cells that present antigen to the B cells
  
• tingible body macrophages that engulfed dead B cells that have died by apotosis

Functional aspects:  resting B cells enter the lymph node parenchyma though the high endothelial venules and if they encounter an antigen with which they can react, they then enter the cycle of blast transformation to produce clones of plasma cells and B memory cells. This production of clones occurs in the germinal centers of lymphoid follicles.

Paracortical zone - deeper regions of the cortex contain primarily T lymphocytes that do not form into follicles.  T lymphocytes (helper and cytotoxic/suppresor) arrive through the circulation, enter the lymph node parenchyma through the high endothelial venules and take up residence in the paracortical zone.  If activated, the T lymphocytes undergo active proliferation to produce expanded clones of activated T lymphocytes.  

Functional aspects: T lymphocytes that arrive at the lymph node via the arterial blood stream gain access to the parenchyma of the lymph node through the wall of the high endothelial venules located in the paracortical zone.  These blood vessels contain endothelial cells that are expressing specific lymphocyte binding molecules called addressins.  These surface molecules are available to bind to lymphocytes that recognize them, the lymphoctyes bind to the surface of the endothelium, then cross the vessel wall and enter the lymph node parenchyma.

Micrographs of lymph node of a cat. (Lab slide 205)

Mantle zone (corona) - The germinal center is surrounded by a ring of darker-staining cells.  The condensed nature of their nuclei indicates that these  are resting B cells. Also present in the mantle zone are T helper cells, macrophages and dendritic cells.

In a T cell-dominated response, the paracortical zone of the lymph nodes may be greatly enlarged. Interdigitating dendritic cells are the main antigen presenting cell in the paracortical zone.

The medulla of a lymph node is composed of medullary cords interspersed between medullary sinuses. 

 The medullary cords are composed of  plasma cells producing  antibodies, their precursors, macrophages and T helper cells. The most prominent cell in the cord is the precursor to plasma cells or immunoblasts that came from the germinal centers of the lymphoid follicles in the cortex of the node.

In the medullary cords, the plasma cells undergo final maturation and secrete antibodies into the lymph that is collected by efferent lymphatic vessels in the node and eventually carried to the general circulation.  Plasma cells may also get into the general circulation in this manner.

Micrographs of lymph node of a cat showing medullary sinuses and cords. (Lab slide 205)

The medullary sinuses are composed primarily of reticular fibers (RF) providing the support framework, reticular cells (fibroblast-like cells that secret the reticulin) (RC) and  macrophages.