The Tissues and Organs of the Lymphatic System
The lymphatic system is a specialized form of connective tissue. It consists of groups of cells, tissues and organs that monitor body surfaces and internal fluid compartments and react to the presence of potentially harmful antigenic substances. These substances include infectious micro-organisms, toxins, foreign cells and tissues, as well as normal cells that have transformed into cancer cells and are recognized as "non-self". Lymphatic tissue constitutes the second line of defence against invaders. The first line of defense is the epithelial covering of the skin, and the gastrointestinal, respiratory and urogenital tracts.
Lymphocytes are the chief cellular constituents of lymphatic tissue and are the key element in an immune response. Functionally, there are two types of lymphocytes, B lymphocytes and T lymphocytes. Both types differentiate from precursors called colony-forming units (CFUs) that originate in early fetal life in the yolk sac, liver and spleen. By late fetal life, CFUs are restricted to the bone marrow, where they continue to proliferate during postnatal life.
Differentiation of Lymphatic Tissue
Primary Lymphatic Organs and Tissues
Undifferentiated stem lymphocytes migrate to the primary lymphatic organs and tissues where they undergo differentiation into immunocompetent cells. This process entails the synthesis of unique internal and membrane proteins. This initial proliferation and differentiation is antigen-independent, and gives rise to populations of cells in which individual cells are genetically pre-programmed to recognize only one antigenic determinant. B and T lymphocytes undergo differentiation in different areas.
T lymphocytes or T cells undergo differentiation in the thymus (hence "T"). They have a long life span and are involved in cell-mediated immunity.
B lymphocytes or B cells undergo differentiation in special microenvironments in the bone marrow. Recent evidence suggests that the lymphatic tissue of the cecum, appendix and ileum is also involved. These areas of the bone marrow and gut-associated lymphatic tissue (GALT) are sometimes called the "bursa equivalent" areas, after the bursa of Fabricius, a mass of lymphoid tissue associated with the cloaca, in birds. B cells got their name because B cell differentiation was first demonstrated in the bursa of Fabricius of chicken embryos. B cells are involved in humoral immunity and the production of antibodies.
To summarize: The primary lymphatic organs are the thymus (for T cells) and bone marrow and probably specific areas of GALT, collectively called bursa equivalent, (for B cells). The primary lymphatic organs are sometimes called the central lymphatic organs.
Secondary Lymphatic Organs and Tissues
Immunocompetent lymphocytes enter the blood and lymph systems to be transported throughout the body. Together with plasma cells, derived from B lymphocytes, and macrophages, they organize around mesenchymal reticular cells and their reticular fibres to form the secondary lymphatic organs (also called the peripheral lymphatic organs). The secondary lymphatic organs and tissues are lymph nodules, the lymph nodes, tonsils and spleen. Immunocompetent lymphocytes also travel to the diffuse connective tissue (lamina propria) that underlies the epithelium of the digestive, respiratory and urogenital tracts.
The mechanisms of the immune responses will not be discussed here.
Histology of the Lymphatic Organs and Tissues
Note: The structure of bone marrow is covered in Hematology and will not be described here.
Diffuse Lymphatic Tissue
Figure
1 
shows the diffuse lymphatic tissue of the lamina propria underlying the
epithelium in an intestinal villus. The lamina propria is a loose connective
tissue consisting of abundant cells and ground substance. The ground substance
is not preserved in routine histological preparations. The cells are primarily
lymphocytes, although plasma cells, macorphages, eosinophils, fibroblasts and
other cell types are also present. Some of the individual cells are indicated
(they are labelled as lymphocytes although at this magnification they can’t
really be identified with certainty). Other structures that are found in the
lamina propria of a villus are also idicated (eg, the central lacteal, which
is a lymph vessel draining the villus, and a strand of smooth muscle
associated with it that allows the villus to contract).
The diffuse lymphatic tissue underlying the epithelia of various organ systems is important in monitoring against invaders. In the event that a lymphocyte reacts with an antigen, it travels to a regional lymph node and undergoes proliferation and differentiation. Its progeny then return to the lamina propria as effector B or T lymphocytes, plasma cells and memory cells. The regular presence of large numbers of plasma cells (especially in the lamina propria of the GI tract) indicates local antibody secretion.
Lymph Nodules
Sometimes lymphocytes form localized concentrations that are sharply defined but not encapsulated. Such concentrations are called lymph nodules. They are common in the walls of the alimentary canal, respiratory passages and urogenital tract, as well as other parts of the body. For the most part, such nodules are disposed singly and in a random manner. However, in the alimentary canal aggregations of nodules are found in specific regions, notably the appendix and cecum and in the Peyer’s patches of the ileum.
A nodule consisting mainly of small lymphocytes is called a primary nodule. A primary nodule appears uniformly dense or colored. Many nodules however, are secondary nodules, containing a lighter-staining central region called the germinal centre, and an outer ring of small lymphocytes. The germinal centre develops when a lymphocyte that has recognized an antigen returns to a primary nodule and undergoes blastic transformation. It is lighter-staining due to the presence of large lymphocytes (lymphoblasts and plasmablasts). Frequently, mitotic figures can be observed here, reflecting the proliferation of new lymphocytes.
Figure
2 shows a row of three lymph nodules in the submucosa of the appendix. The
middle one is not quite as well defined as the other two, and appears to be
budding off the lower nodule. A small germinal centre can be seen in the lower
nodule.
To the right of the lymph nodules, the diffuse lymphatic connective tissue of the lamina propria can be seen between the mucosal glands (crypts).
Lymph Nodes
Lymph nodes are small, encapsulated lymphatic organs located along lymphatic vessels. They are bean-shaped, with a convex and a concave surface. They range in size from 1 mm to about 2 cm along their longest dimension. They serve as filters through which lymph percolates on its way to the blood. Although they are widely distributed, they are concentrated in certain areas, such as the groin, axilla, and mesenteries.
Supporting Framework of Lymph Node
The lymph node is covered by a capsule of dense connective tissue. Trabeculae, also made of dense CT, extend from the capsule into the substance, forming the gross framework of the node. A fine supporting meshwork of reticular fibres (made of collagen type III) is found throughout the remainder of the gland. Reticular fibres are not seen in routine preparations, but can be seen with special stains, eg. silver stains. The reticular fibres are secreted by reticular cells, which are stellate or elongate cells with an oval nucleus and a small amount of acidophilic cytoplasm. Cytoplasmic processes of reticular cells wrap around the bundles of reticular fibres, isolating them from the lymphocytic parenchyma.
Although they can’t be distinguished with the light microscope, two populations of reticular cells have been identified by electronmicroscopy, immunocytochemistry and autoradiography. The first population, as described above, has a structural function. The second population of reticular cells, also called dendritic cells, has functions characteristic of antigen-presenting cells or tissue macorphages. These cells are splayed along the meshwork of reticular fibres to increase the surface area for phagocytosis and other cell interactions.
N.B.: The supporting meshwork of reticular fibres produced by reticular cells and enveloped by the cytoplasmic processes of those cells, is typical of lymphoid organs in general (so it won’t be described for each one) WITH THE EXCEPTION OF THE THYMUS (discussed below). Other lymphoid organs also have the two populations of reticular cells (secretory and antigen-presenting).
Organization of Parenchyma of Lymph Node
The parenchyma of the lymph node is separated from the capsule by a sinus, the subcapsular (or marginal or cortical) sinus. The subcapsular sinus is continuous with sinuses that extend along the trabeculae, called trabecular sinuses.
The parenchyma of the lymph node is divided into a cortex and a medulla. The cortex forms the outer part of the node, except at the hilum. It consists of a dense mass of lymphatic tissue. In the outer part of the cortex, the lymphocytes are typically organized into nodules which consist mainly of B cells. The part of the cortex adjacent to the medulla is not organized into nodules. It is called the deep cortex (or juxtamedullary cortex, or paracortex). It is dependent on T cells for its development, and perinatal thymectomy results in a poorly developed paracortex. For this reason, it is also called the thymus-dependent cortex.
The medulla forms the inner part of the lymph node. It consists of cords of lymphatic tissue, separated by lymphatic sinuses called medullary sinuses. The medullary sinuses are continuous with the trabecular sinuses of the cortex. They converge toward the hilum, where they drain into efferent lymphatic vessels. The medullary cords consist mostly of B lymphocytes.
Lymphatic and Blood Supply of Lymph Node
Afferent lymphatic vessels penetrate the capsule at various points on its convex surface. Lymph flows into the subcapsular sinus and through the trabecular and medullary sinuses toward the efferent lymphatic vessels. Efferent lymphatic vessels leave at the hilum, a depression on the concave surface, which also serves as the entry and exit for blood vessels and nerves.
The spaces of the sinuses are crossed by a network of reticular fibres, reticular cells, and macrophages. Potential antigens, such as macromolecules, bacteria, parasites, or tumoral cells reaching the node through the afferent lymphatics are usually trapped in this network and processed by macrophages.
The sinuses have a lining of endothelium that is continuous when it is directly adjacent to the connective tissue of the capsule or trabeculae (septa), but discontinuous when it faces the lymphatic parenchyma. Lymphocytes and macrophages readily pass back and forth between the sinuses and parenchyma. A macrophage in the parenchyma may also send long cytoplasmic processes, called pseudopods, into a sinus through endothelial discontinuities to monitor the lymph percolating through.
Arteries enter at the hilum and progress toward the cortex, forming capillary beds around the cortical nodules. Postcapillary venules progress back toward the hilum, becoming larger and converging onto the vein as they do so. Postcapillary venules are lined by an unusual cuboidal or columnar epithelium. This extra-tall epithelium allows lymphocytes to pass through the vessel by diapedesis but prevents the passage of fluid. In fact, most lymphocytes enter the node through the postcapillary venules, although some enter with the lymph of the afferent lymph vessels. Antigen-transformed lymphocytes remain in the lymph node to proliferate and differentiate. T cells remain in the thymus-dependent paracortex, while B cells migrate to the nodular cortex. Most lymphocytes leave the lymph node by entering a lymphatic sinus from which they reach the efferent lymphatic vessels.
Figures for Lymph Nodes
We have 2 slides of lymph nodes, slide 31 and slide S31. Slide 31 is an active lymph node, and some morphological features are difficult to see. On many of the slides (#31), the section seems to have largely missed the medulla and shows mainly cortical tissue. Slide S31 is made from an inactive lymph node, and the organization of the node is easier to see.
Figures 3 to 7 are made from slide 31 (active lymph node).
Figure
3 shows a low power view of the cortical area of the lymph node. The
capsule is at the left. Sections of septa (or trabeculae) that extend from the
capsule lie within the cortex. The supporting meshwork of reticular fibres is
not evident without special stains.
The subcapsular sinus can be seen directly beneth the capsule. It continues into a trabecular sinus running alongside an unlabelled septum at the upper left. The parenchyma of the cortex is filled with lymphocytes and other cells. In this section, the organization of the cortex into nodules is not evident.
The
organization of the nodule can be seen slightly better in Figure 4. The
subcapsular sinus is easily identified, and a lymph nodule, with a slightly
eccentric germinal centre, lies in the middle of the field of view. It is
surrounded by sections of trabeculae (asterisks).
Figure 5
shows an area of the medulla (hard to find on many of your slides). Cords of
lymphatic tissue are separated by the medullary sinuses. The lighter-staining
medulla is surrounded by an area of darker-staining paracortex (except at the
bottom of the field of view). Sections of septa are seen in the paracortex.
Figure
6 shows a close-up of the subcapsular sinus. Blood vessels can be seen in
the adjacent cortex. Notice the lymphocyte infiltration of the capsule.
Reticular cells are very hard to find in standard sections. Look for a cell in which you can identify a nucleus and some cytoplasm. The nucleus should be ovoid and pale-staining. The cytoplasm is acidophilic. You will only have a hope of finding reticular cells in areas where the lymphocytes are less densely packed, that is, in the sinuses and medulla.
Figure
7 shows a close-up from the medulla. Two possible reticular cells (the
lower one is better) and a possible macrophage are indicated.
Figures 8 to 10 are made from slide S31 (inactive lymph node).
Figure 8
shows a low power view of the lymph node. The capsule blends into the adjacent
connective tissue, in which blood vessels can be seen. The different parts of
the lymph node can be much more readily identified in this slide. A row of
lymph nodules of different sizes is seen below the subcapsular sinus.
Individual lymph nodules in the cortex of a node are distinct, although they
may sometimes blend into one another. The paracortex appears as a band of
solid lymphatic tissue. No paracortex is evident on the right-hand side of the
figure. The hilum is toward the lower left. The thickness of the various areas
(cortex, paracortex, medulla) will vary as you scan your slide on low power.
Figure
9 shows a high power view of the cortex. A septum is seen arising from the
capsule and extending between some nodules in the cortex. The continuity of
the subcapsular sinus and trabecular sinuses is seen in this section.
Figure
10 shows a high power view of the medulla and adjacent paracortex. The
boundary is indicated by asterisks. The paracortex appears as a fairly uniform
mass of lymphatic tissue, while in the medulla, cords of lymphatic tissue are
separated by sinuses. Notice that cells are present even in the sinuses.
Tonsils
Tonsils are organs composed of aggregates of incompletely encapsulated lymphoid tissue. They are characterized by depressions of surface epithelium around which aggregations of lymph nodules are grouped. Three consular groups, the palatine tonsils, lingual tonsils, and pharyngeal tonsils, form a ring of lymphoid tissue surrounding the pharynx where the nasal and oral passages unite.
Tonsils aid in the protection of the body against invading bacteria, viruses, and foreign proteins. The antigens stimulate the production of antibodies in plasma cells derived from lymphocytes. However, epithelial erosion seems to enhance an invasion by microorganisms, and the tonsils are frequent portals of infection.
Tonsils reach their maximum development in childhood, and thereafter form an incomplete ring around the pharynx. The palatine (or faucial) tonsils are paired, ovoid structures located in the mucous membrane at the junction of the oropharynx and oral cavity (faucia). The lingual tonsils are small and fairly numerous structures located in the root of the tongue, behind the circumvallate papilla. The pharyngeal tonsil is a single tonsil located in the median posterior wall of the nasopharynx. (Extensions of the pharyngeal tonsil around the pharyngeal orifices of the eustacean tubes are sometimes considered as separate tonsils, the tubal tonsils.) Here, we will only look at the palatine tonsils.
The Palatine Tonsils
The palatine tonsils are covered on their free surface with stratified squamous epithelilum that is continuous with the lining of the mouth and pharynx. The epithelium rests on a basement membrane, under which there is a thin layer of fibrous connective tissue. In about 10 to 20 places, the epithelium covering the tonsil dips into the interior of the tonsil, forming tonsillar crypts. The crypts are lined with a continuation of the stratified squamous epithelium. The lumens of the crypts contain desquamated epithelial cells, live and dead lymphocytes, and bacteria.
Lymphoid tissue surrounds the crypts as a diffuse mass in which lymph nodules are embedded. The nodules may contain germinal centres. In the deeper parts of the crypts, there is an intense infiltration of the epithelium with lymphocytes, and consequently no clear delineation between epithelium and lymphoid tissue. Adjacent to the deepest portions of the tonsil, the fibrous tissue is condensed to from a thin capsule that covers the base and sides of the tonsil. The capsule acts as a barrier against spreading tonsillar infections. Connective tissue septa extend into the interior of the tonsil and separate the various crypts, with their surrounding lymphatic tissue, from one another. Small mucous glands lie in the connective tissue beneath the tonsil and its capsule; their ducts usually open on the free surface, occasionally into the crypts.
Tonsils possess no afferent lymphatic vessels. Lymphoid tissue is supplied from blood vessels coursing in the capsule and septa of the tonsils. Plexuses of lymph capillaries occur around the lymphoid tissue and drain into efferent lymphatic vessels.
Figures for Tonsils
Figure 11
shows the general structure of the palatine tonsil at low power. A crypt lined
with stratified squamous epithelium runs along the lower left (hard to
identify at this magnification). The lymph nodules embedded in the diffuse
lymphoid tissue surrounding the crypts can readily be identified. The large
spaces toward the upper right are artifacts caused by damage to the tissue.
Figure
12 is very similar to Figure 11. In this case, the low power view is of
lymph nodules in the diffuse lymphoid tissue lying beside a connective tissue
septum (orange). These septa extend from the capsule in the deep part of the
tonsil toward the interior of the tonsil.
Figure 13
shows a higher power view of a cleft extending from the surface toward the
inside of the tonsil. Because of damage to the tissue, the lumen of the cleft
is not well-defined. (Even when not damaged, clefts are usually filled with
debris as described above.) Nodules are not easily identified in the lymphoid
tissue within the field of view. The separation of the lymphoid tissue from
the lower surface of the cleft is an artifact.
Figure
14 is a high power view of the stratified squamous epitherlium covering
the free surface and clefts of the tonsil. The epithelium is frequently more
infiltrated with lymphocytes than appears to be the case here. A layer of
fibrous connective tissue underlies the epithelium.
The Spleen
The spleen is the largest of the lymphoid organs. It is located in the upper left of the abdominal cavity and has a rich blood supply. While lymph nodes serve as the immunological filter of the lymph, the spleen serves as the immunological filter of the blood. It is an important defense against microorganisms that penetrate the circulation.
General Sructure
The spleen is surrounded by a capsule, which itself is covered by a serous membrane, the peritoneum. Many trabeculae pass from the capsule into the interior of the organ. On the medial surface of the spleen is a deep indentation, the hilum, which provides for the passage of the splenic artery and vein, lymph vessels and nerves. The capsule and trabeculae are made of dense connective tissue that contains myofibroblasts. These cells are contractile and also produce the extracellular CT fibres. In those species in which the spleen has the capacity to hold a large volume of blood (not humans), contraction of the capsule and trabeculae helps discharge stored RBCs into the circulation.
The trabeculae, which branch and anastomose repeatedly, delineate many compartments, or lobules, within the spleen. Each lobule is bounded by several trabeculae, but the lobules are not distinct because they are not completely outlined by trabeculae. Each lobule is supplied by a central artery (described below) and drained by veins that run in the trabeculae to leave the lobule.
The parenchyma of the spleen is supported by a fine meshwork of reticular fibres that blends with the capsule, trabeculae and walls of blood vessels. Reticular cells (as described for lymph nodes) and macrophages are associated with the reticular fibres.
White Pulp and Red Pulp
The substance of a freshly cut spleen appears as two colors. Circular or elongated whitish-gray areas are surrounded by more reddish areas. These areas are called the white pulp and the red pulp, respectively. The white pulp consists of aggregations of lymphocytes, the red pulp consists of cords of cells separated by sinusoids.
Branches of the splenic artery course through the capsule and trabeculae and enter the parenchyma. The arteries, whose adventitia is largely replaced by reticular tissue, immediately become enveloped by a sheath of lymphocytes. This lymphocyte sheath is called the periarterial lymphatic sheath (PALS). It constitutes the white pulp, and the artery inside is called the central artery. In cross section, the sheath of lymphocytes appears circular and may give the appearance of a nodule; however, the presence of a central artery distinguishes PALS from a nodule. Nodules do, however, appear along the length of the periarterial lymphatic sheath. They appear as localized expansions of PALS and tend to displace the central artery. In cross sections of PALS with a nodule, the central artery has an eccentric, rather than a central position. The central artery sends branches into the PALS and to the sinus (called the marginal sinus, see below) surrounding the PALS.
The nodules of the white pulp consist of B lymphocytes, while the non-nodular PALS ensheathing the central artery consists of T lymphocytes (and is therefore a thymus-dependent zone). The nodules often have a germinal centre, which, as in other lymphatic tissue, is a response to antigen exposure. The periarterial lymphatic sheath is surrounded by a margin of less densely packed lymphoid tissue with many sinuses called the marginal zone. The marginal zone has fewer lymphocytes but many macrophages that show active phagocytosis. This zone plays a major role in the immunologic activity of the spleen. The perimeter of the white pulp is bounded by a sinus called the marginal sinus. Don’t expect to be able to distinguish the marginal sinus on your slides.
The red pulp consists of cellular cords, called splenic cords or Billroth's cords, which form a spongy network of modified lymphatic tissue that gradually merges into the white pulp. Separating the cords are venous sinuses. The splenic cords are supported by the typical meshwork of reticular cells and fibres that contains large numbers of RBCs, macrophages, lymphocytes, plasma cells and granulocytes. The macrophages phagocytose (among other things) damaged RBCs. They begin the process of hemoglobin breakdown and iron reclamation. The iron is stored as ferritin or hemosiderin to be reutilized in the formation of new RBCs. It will be transported, in combination with transferrin, to the bone marrow to be reused in erythropoiesis. The heme is broken down into bilirubin, to be transported to the liver via the portal system and there conjugated to glucuronic acid, which is secreted into the bile. Globin, the protein part of hemoglobin, is hydrolized to amino acids that are reutilized for protein synthesis. Of all the phagocytes in the body, the splenic ones are also the most active in the phagocytosis of living particles such as bacteria and viruses.
The endothelial cells that line the sinuses of the red pulp are extremely long, and their long axes parallel the direction of the vessel. Electron microscopy has revealed that these rod-like endothelial cells are only intermittantly connected to one another by side processes and that they do not have a continuous basement membrane. Rather, strands of basement membrane loop around the outside of the sinus at right angles to the long axes of the endothelial cells, like hoops around the staves of a barrel. Thus, there are prominent intercellular spaces between the endothelial cells. Processes of macrophages extend between the endothelial cells and into the lumen of the sinuses to monitor the passing blood for antigens. Blood is also able to pass into and out of the sinuses quite easily. Blood fills both the sinuses and the cords of the red pulp, often to such an extent that it is difficult, in (light microscopy) histological sections, to distinguish between the cords and the sinuses.
Splenic Circulation - Open and Closed Models
After numerous divisions, the arterioles of the PALS lose their investment of white pulp and enter the red pulp. Here each arteriole divides into several small branches that lie close together, like a brush or penicillus. These arterioles are called penicilli or penicillar arterioles. The penecilli continue as arterial capillaries. They may become surrounded by aggregations of macrophages, in which case they are called sheathed capillaries. The macrophages ingest blood-borne particles.
The manner in which blood flows from the arterial capillaries in the red pulp into the interior of the sinuses has not been completely elucidated. Some investigators believe that the capillaries open directly into the sinusoids; they are proponents of the closed circulation model. Other investigators believe that the blood empties directly into the reticular meshwork of Billroth's cords. The blood would then percolate throught the cords and be exposed to their macorphages before returning to the circulaton by entering a sinus from the extravascular side. This is the open circulation model.
The open circulation model is currently the most favored. It provides a more efficient exposure of blood to red pulp macrophages. In the closed circulation model, blood cells would have to leave the sinuses and then reenter them in order to be exposed to macrophages. All investigators agree that blood cells do leave the vasculature to populate the red pulp and white pulp and that they reenter the vascular system in the red pulp. (The sinuses, as described above, are very leaky.)
The venous sinuses empty into the pulp veins that leave the pulp and unite to form larger veins which pass into the trabeculae as trabecular veins. The trabecular veins (consisting only of endothelium and the fibromuscular tissue of the trabeculae) travel to the hilum, where they drain into the splenic vein.
Lymphatic vessels originate in the white pulp near the trabeculae and constitute a route for lymphocytes to leave the spleen. Efferent vessels are present in the larger trabeculae and capsule. The spleen has no afferent lymphatic vessels.
Functions of the Spleen
The spleen functions in both the immune and hematopoetic systems.
Its immune functions include:
- proliferation of lymphocytes
- production of humoral antibodies
- removal of macromolecular antigens from the blood
Its hematopoetic functions include:
- formation of blood cells in fetal life
- removal and destruction of senile, damaged and abnormal RBCs and platelets
- retrieval of the iron from hemoglobin
- storage of blood in some species (not humans)
Despite its many functions, the spleen can be removed surgically if necessary, for example, if trauma causes intractable bleeding from the spleen. The destruction of RBCs then occurs in the bone marrow and liver.
Figures for the Spleen
We have 2 slides to show the parenchyma of the spleen, slides #34 and #71. Both are from monkey, but the tissue in slide #71 was fixed by perfusion, and the sinuses are more distended. Figures 15 – 19 are from slide #34.
Figure 15
shows a low power view of the spleen. Areas of white pulp and red pulp are
readily identifiable. Lymph nodules can be seen in the white pulp; some, like
the one labelled at the right, have large germinal centres. (At this
magnification, it might be hard to distinguish PALS with a central artery from
lymph nodules; however, a light central area surrounded by a dark ring
suggests that it is a lymph nodule. Compare the lymph nodule with the white
pulp to the left of it.) Trabeculae (septa) containing blood vessels are also
seen.
Figure
16 shows a medium power view of white pulp surrounded, above and below, by
red pulp. Three areas of PALS with a central artery are seen in the middle of
the field of view. The PALS at the far right seems to have a small nodule with
a germinal centre. White pulp, which may be a nodule, is also seen at the top
right.
Figure
17 shows a high power view of a central artery within the PALS. The
structure to the left is likely a branch from the central artery.
Figure
18 shows the red pulp of the spleen. The cords and sinuses seem kind of
squeezed together. However, red blood cells, which are a bit more brightly
colored than the surrounding cords, can be seen in the sinuses. Some (not all)
of the sinuses are labelled. Billroth’s cords run between the sinuses.
Figure
19 is similar to Figure 18. In addition to the cords and sinuses, a
section of a connective tissue septum is seen.
Figure
20 is taken from the slide of perfused monkey spleen (slide #71). The
sinuses are more dilated (and therefore more distinct from the cords) with
fewer red blood cells.
Figure 21
is from a special slide (#73) prepared with Cajal’s reticulin stain to show
the distribution of reticular fibres. Strands of the dark-staining reticular
fibres can be seen throughout the parenchyma. They appear as fine wavy lines.
Sometimes you will see a concentration of them, as indicated by the 2 arrows
at the left. Those bands of fibres are probably surrounding blood vessels. Don’t
look for cellular details in this slide.
The Thymus
The thymus is a 2-lobed organ located in the upper mediastinum anterior to the heart and great vessels. The two lobes are united by connective tissue. The thymus varies in size and development with the age of the individual. It attains its maximum development after puberty, after which it becomes inconspicuous. Much of the thymus tissue eventually becomes replaced with adipose tissue.
The thymus is the site where stem lymphocytes proliferate and differentiate into T cells. During fetal life, the thymus becomes populated by functionally immature (stem) lymphocytes arising from the yolk sac, liver and spleen. In late fetal life, bone marrow becomes the source of these lymphocytes. The transformation of immature lymphocytes to T cells is promoted by a humoral factor called thymosin. Thymosin is believed to be produced by epithelioreticular cells (see below).
Within the thymus, there is large-scale proliferation of cells and large-scale cell death. Most newly formed lymphocytes die within a few days. Nevertheless, large numbers of T lymphocytes are released and carried by the blood to the lymph nodes, spleen, and other lymphatic organs and tissues, where they occupy specific areas. Under proper stimulation, the T cells proliferate and participate in cell-mediated immune response. T cells survive for long periods and recirculate through lymphatic tissue.
Structure of Thymus
Each thymic lobe is composed of thousands of lobules, each of which has an outer cortical and inner medullary component. A capsule encloses each lobe, and septa extend from it as far as the medulla to delineate the lobules. The lobules are not completely separate, because the medullary components of different lobules are continuous with one another. The capsule and septa contain blood vessels, efferent lymph vessels (but no afferent lymph vessels), and nerves.
Lymphocytes are the predominant cell type in the thymus, but plasma cells, granulocytes, mast cells, and fat cells are also present. Macrophages are numerous, especially in the cortex. The framework for the thymic parenchyma is provided by epithelioreticular cells. These cells arise from endoderm, unlike the reticular cells of other lymphatic organs, which arise from mesenchyme. During development, the epithelium of the thymus (which arises as a paired ventral outgrowth from the third pharyngeal pouch) invaginates into and soon obliterates the lumen. Stem lymphocytes invade and occupy the spaces between the epithelial cells. Some of these epithelial cells give rise to the epithelioreticular cells. Despite the large numbers of lymphocytes, the epithelioreticular cells remain joined to one another by desmosomes at the end of long cytoplasmic processes. As a consequence, they assume a stellate shape. They posess ovoid, pale-staining nuclei with a distinct nucleolus.
The epithelioreticular cells correspond to the reticular cells and their associated reticular fibres in other lymphoid tissue in providing a framework. However, the reticular cells of the thymus do not produce any reticular fibres.
Unlike other lymphoid organs, the lymphatic tissue of the thymus is not arranged in nodules. The outer portion, or cortex, of each thymic lobule contains a high concentration of small lymphocytes, also called thymocytes. The inner portion, or medulla, contains a lesser concentration of lymphocytes. In addition to thymocytes, medium and large lymphocytes may also be present. Thus the cortex appears dark-staining, and the medulla appears lighter staining. Because of the density of lymphocytes in the cortex, it is almost impossible to identify reticular cells there; they can sometimes be seen in the medulla. In some tissue sections, the continuities between the medullas of different lobules can also be seen.
Structures called Hassall's corpuscles are a distinctive feature of the thymus. Hassall's (or thymic) corpuscles are isolated masses of concentrically arranged epithelioreticular cells. Their centre may display evidence of keratinization. They are acidophilic and become more prominent during periods of intense destruction of thymocytes and during involution. They are more common in the medulla.
The Blood-Thymic Barrier
Arteries entering the thymus branch and travel along the trabeculae. Arterioles enter the lobules at the junction of the cortex and medulla. Numerous capillary branches pass into the cortex, and less regular branches pass into the medulla. In the medulla, blood vessels carry with them a sheath of loose connective tissue. In the cortex, the perivascular connective tissue sheath becomes ensheathed in epithelioreticular cells. A basement membrane is frequently interposed between the CT and the epithelioreticular cells. These various layers form a blood-thymus barrier in the cortex. From the lumen outward, the layers of the blood-thymus barrier are: the capillary endothelium, the basement membrane of the endothelium, a thin perivascular CT sheath containing many macrophages, the basement membrane of the epithelioreticular cells, the epithelioreticular cell sheath. The endothelium itself has been shown to be highly impermeable to macromolecules.
The capillaries in the medulla drain into venules, which also receive the capillaries returning from the cortical zone. (Capillaries are the only kind of blood vessels in the cortical zone.) The medullary veins enter the connective tissue septa and leave the thymus through the capsule.
There are no afferent lymph vessels in the thymus, which therefore does not act as a lymph filter, as do lymph nodes. Efferent lymph vessels are few, and are located in the walls of blood vessels and in the CT of the septa and capsule.
Figures for the Thymus
A low power
view of the thymus is seen in Figure 22. Several septa can be seen
extending from the capsule into the cortex, dividing it into lobules. The
cortex stains a blue-purple color, while the medulla stains red-purple. The
continuity of the medullas of the various lobules is evident. Sometimes, as a
result of sectioning, the medulla of a lobule may appear as an isolated
circular area. When that happens, it looks like the germinal centre of a lymph
nodule. Such a phenomenon is not obvious in this figure.
Figure 23
shows a higher power view of the thymus. Several lobules separated by
connective tissue septa are seen. The lobule in the centre of the field of
view gives the appearance of a nodule with a germinal centre. However, the
prominent Hassall’s corpuscle of the lobule to its lower right (that looks
like it is budding off the first lobule) would alert you to the fact that this
is a section of the thymus. While the central lobule has an easily
distinguishable cortex and medulla, most of the surrounding lobules show only
cortex. The lobule with the Hassall’s corpuscle shows a small amount of
medulla around the corpuscle.
Figure 24
shows a Hassall’s corpuscle at higher magnification. Although they are made
of concentrically arranged epithelioreticular cells, Hassall’s corpuscles
often appear amorphic. They are intensely eosinophilic.
Figure 25
shows some (probable) epithelioreticular cells in the medulla. In additon to
thymocytes (small lymphocytes), small and large lymphocytes, and other cell
types as described in the text, may be present. To identify epithelioreticular
cells, look for large, pale-staining nuclei. If you are incredibly lucky, you
might see some cytoplasm with processes extending from it (not seen here).
Macrophages are also abundant. They are difficult to distinguish from the
epithelioreticular cells, and we don’t try. (They could be identified if
they happened to have ingested something that would stand out in the
sections.)
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