Lymphatic System

The thymus is entirely composed of T cells, epithelial reticular cells and some macrophages. Occasionally another type of cell will get into the thymus, but it does not belong there. The thymus consists of a cortex and medulla with no germinal centers. Immature T cells are found at the edges of the cortex. As they mature, they migrate deeper into the cortex and eventually leave as mature naïve T cells through the venules of the medulla. In the lymph node, the cortex is made of primary follicles of resting B cells and secondary follicles with germinal centers. The germinal centers are where B cells are undergoing clonal expansion, after binding antigen and receiving T cell help. Most T cells are located deeper in the cortex. Antigen-stimulated helper T cells are formed when antigen is presented to them by dendritic cells (and possibly macrophages), deep in the cortex. B cells also bind their antigen in this region. B cells entering the lymph node travel through the cortex to a follicle. If they have bound antigen in the cortex, they attract antigen-stimulated T helper cells to the follicle, where T cell help occurs. T cell help in the spleen occurs in the PALS. Close to, if not touching, the PALS are follicles of resting B cells, a clone of which may give rise to a germinal center upon proper stimulation.

These are the stellate shaped fibroblasts found in the lymph node that are involved in making reticular (type III collagen) fibers. They are NOT the same as the epithelial reticular cells found in the thymus: epithelial reticular cells s are true epithelial cells derived from the endodermal lining of the third pharyngeal pouch in the embryo (the third pouch is what gives rise to the thymus) whereas reticular cells, like most connective tissue fibroblasts, are derived primarily from mesoderm.

Nowhere. Once a plasma cell differentiates in the lymph node, it generally migrates to a medullary cord in the medulla of the lymph node and begins secreting antibodies that travel throughout the body (first through efferent lymphatics that then drain into venous blood). Once in the medullary cord, the plasma cell generally stays puts. It is worth noting that plasma cells are rarely observed in peripheral blood. The numerous plasma cells found in various tissues in the body traveled in the circulation as naive B lymphocytes until they were stimulated to enter the peripheral tissue and differentiate into a plasma cell locally.

There are many adhesion molecules and receptors expressed both by the high endothelial post capillary venules of the lymph node and on the B and T lymphocytes that allow them to enter the lymph node. This process is called "lymphocyte homing". When appropriate signals are received, cells begin to cross the endothelial cells of the venules. Finally they reach the deep cortex where they can receive T cell help and continue on to the follicles.

With their dark staining nuclei and little cytoplasm, the abundant T lymphocytes in the cortex give the thymus a dark color. The thymic medulla has far fewer lymphocytes in it and so stains much lighter.

Lymph nodes are filled with reticular cells and fibers. The fibers, made by reticular cells (which are related to fibroblasts) and composed of type III collagen, form a supportive meshwork for lymphocytes and other cells in the cortex and medulla. Reticular cells in the lymph node wrap around the reticular fibers (they are extracellular fibers). This same reticular fiber support is found in the spleen and tonsil as well as the bone marrow. The thymus has epithelial reticular cells. Like reticular cells elsewhere, thymic epithelial reticular cells provide support in the cortex and medulla. Unlike reticular cells, epithelial reticular cells have keratin filaments and are joined by desmosomes. Epithelial reticular cells (which, unlike reticular cells, are true epithelial cells) help make the blood-thymus barrier in the thymic cortex and provide a microenvironment in the thymus for T cells to develop. They also play a crucial role in positive and negative selection of T-cells.

To leave the thymus, lymphocytes must survive negative selection to enter the thymic medulla. From the medulla, they intravasate by crossing the walls of venules located at the cortico-medullary junction. Alternatively, they may leave the thymus via efferent lymphatic vessels. There are generally no afferent lymphatic vessels in the thymic cortex because this might allow free antigens to enter the cortex thereby impinging on the positive selection process.

The spleen has two main functions in the body. First, it is a lymphoid organ, providing a place for T cell help and B cell differentiation. This occurs in the white pulp of the spleen. The spleen also serves as a filter of the blood. Arterioles flowing into the cords of the red pulp end and the blood spills into the cords (when blood is not contained in a vessel, it is termed "open circulation"). In order for this blood to re-enter the venous system of the spleen, it must pass from the cords of the red pulp into the sinuses. The walls of the splenic sinuses are made of elongated endothelial cells with transverse running reticular fibers, giving them the look of sheaves on a barrel. These are called "rod cells". Blood cells must wiggle through this "filter" to continue circulating. Those that can't pass through are removed by the macrophages of the spleen.

Lymphoblasts (sometimes called "large lymphocytes") are typically found in the germinal centers of secondary follicles (which, in turn, may be found in mucosa-associated lymphoid tissue --aka MALT, the cortex of lymph nodes, and the white pulp of the spleen). The presence of lymphoblasts gives germinal centers their lighter appearance, both because of their large size and because of their lightly staining, euchromatic nuclei. Recall that heterochromatic or dense, deeply staining nuclei are characteristic of cells with very limited nuclear transcription; whereas euchromatic or lightly staining nuclei indicate the presence of much transcriptionally active chromatin. Thus, lymphoblasts have euchromatic nuclei because they are transcribing many genes as they differentiate into plasma cells and memory B cells.

You shouldn't see macrophages in splenic sinuses, only in the cords. As cells (especially RBCs) age, they lose their agility. This increased stiffness makes it harder for them to wiggle through the small gaps between the endothelial cells of the splenic sinus. Macrophages often occupy these spaces (within the cords) to "clean up" any cells that don't make it through or that are moving very slowly.

The lymph node is composed of follicles surrounding medullary cords and sinuses. A feature that is characteristic of the lymph node is the post capillary, high endothelial venule. You can occasionally see lymphocytes migrating from the blood into the lymph node if you examine the walls of these vessels. In the palatine tonsil you can see large follicles and a stratified squamous epithelium. One feature of the lymphoid tissue of the tonsil and MALT in general is that its follicles have a "starry sky" appearance. This comes from the numerous, light staining macrophages present, along with lymphocytes and plasma cells, in the germinal centers of the tonsil. The spleen consists of areas of red and white pulp. The spleen can be identified by looking for deep staining areas of white pulp surrounding central arteries. These areas are known as the periarterial lymphatic sheath (PALS for short). Germinal centers of the spleen often run along the PALS. The thymus is unique in that it is the only lymphoid organ with no germinal centers. Germinal centers are made up of B cells that are proliferating and preparing to become plasma cells. You should never see B cells in the thymus. It is a place for the maturation of T cells, which then leave the thymus and enter other lymph tissues. The thymus is composed of lobules. One easily recognizable feature of the thymic medulla is the presence of Hassall's corpuscles. The function of these corpuscles is uncertain, although they do secrete IL-4 and IL-7 and therefore certainly influence the development of the thymus and T-cell maturation.

Macrophages are the major APCs in the tonsil and the spleen (although the spleen also has dendritic cells that do this to some extent as well). In the lymph node, dendritic cells are the major antigen presenters, although macrophages in the medullary sinuses also do this to some extent as well.

The thymus is entirely composed of T cells, epithelial reticular cells and some macrophages. Occasionally another type of cell will get into the thymus, but it does not belong there. The thymus consists of a cortex and medulla with no germinal centers. Immature T cells are found at the edges of the cortex. As they mature, they migrate deeper into the cortex and eventually leave as mature naïve T cells through the venules of the medulla. In the lymph node, the cortex is made of primary follicles of resting B cells and secondary follicles with germinal centers. The germinal centers are where B cells are undergoing clonal expansion, after binding antigen and receiving T cell help. Most T cells are located deeper in the cortex. Antigen-stimulated helper T cells are formed when antigen is presented to them by dendritic cells (and possibly macrophages), deep in the cortex. B cells also bind their antigen in this region. B cells entering the lymph node travel through the cortex to a follicle. If they have bound antigen in the cortex, they attract antigen-stimulated T helper cells to the follicle, where T cell help occurs. T cell help in the spleen occurs in the PALS. Close to, if not touching, the PALS are follicles of resting B cells, a clone of which may give rise to a germinal center upon proper stimulation.

These are the stellate shaped fibroblasts found in the lymph node that are involved in making reticular (type III collagen) fibers. They are NOT the same as the epithelial reticular cells found in the thymus: epithelial reticular cells s are true epithelial cells derived from the endodermal lining of the third pharyngeal pouch in the embryo (the third pouch is what gives rise to the thymus) whereas reticular cells, like most connective tissue fibroblasts, are derived primarily from mesoderm.

Nowhere. Once a plasma cell differentiates in the lymph node, it generally migrates to a medullary cord in the medulla of the lymph node and begins secreting antibodies that travel throughout the body (first through efferent lymphatics that then drain into venous blood). Once in the medullary cord, the plasma cell generally stays puts. It is worth noting that plasma cells are rarely observed in peripheral blood. The numerous plasma cells found in various tissues in the body traveled in the circulation as naive B lymphocytes until they were stimulated to enter the peripheral tissue and differentiate into a plasma cell locally.

There are many adhesion molecules and receptors expressed both by the high endothelial post capillary venules of the lymph node and on the B and T lymphocytes that allow them to enter the lymph node. This process is called "lymphocyte homing". When appropriate signals are received, cells begin to cross the endothelial cells of the venules. Finally they reach the deep cortex where they can receive T cell help and continue on to the follicles.

With their dark staining nuclei and little cytoplasm, the abundant T lymphocytes in the cortex give the thymus a dark color. The thymic medulla has far fewer lymphocytes in it and so stains much lighter.

Lymph nodes are filled with reticular cells and fibers. The fibers, made by reticular cells (which are related to fibroblasts) and composed of type III collagen, form a supportive meshwork for lymphocytes and other cells in the cortex and medulla. Reticular cells in the lymph node wrap around the reticular fibers (they are extracellular fibers). This same reticular fiber support is found in the spleen and tonsil as well as the bone marrow. The thymus has epithelial reticular cells. Like reticular cells elsewhere, thymic epithelial reticular cells provide support in the cortex and medulla. Unlike reticular cells, epithelial reticular cells have keratin filaments and are joined by desmosomes. Epithelial reticular cells (which, unlike reticular cells, are true epithelial cells) help make the blood-thymus barrier in the thymic cortex and provide a microenvironment in the thymus for T cells to develop. They also play a crucial role in positive and negative selection of T-cells.

To leave the thymus, lymphocytes must survive negative selection to enter the thymic medulla. From the medulla, they intravasate by crossing the walls of venules located at the corticomedullary junction. Alternatively, they may leave the thymus via efferent lymphatic vessels. There are generally no afferent lymphatic vessels in the thymic cortex because this might allow free antigens to enter the cortex thereby impinging on the positive selection process.