ItalianoColorazioniI tessutiTessuto epitelialeTessuto connettivoEnglishStainingsThe tissuesEpithelial tissueConnective tissue Disclaimer
This is a particular connective tissue, characterized by its structure: it is composed mainly by lymphocytes, cells supported by a dense connective network. The cells composing this tissue originate in organs called primary lymphatic organs. They move in the different parts of the body through blood and lymph circulation (therefore, in blood and lymph connective tissues); they can stop in other lymphatic organs, called secondary lymphatic. Finally, they can leave the vessels and migrate through loose connective tissue. What has been said helps to understand that the cells constituting lymphoid tissue can also be found in various types of connective tissue. This happens because their function is not the typical function of connective tissue (i.e. trophic and supportive), but a protecting function against various pathogens. This function relies on their ability to circulate throughout the body and reach the area containing a pathogen to destroy. They can be found either isolated or, more often, aggregated in more or less organized groups.
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Lymphocytes are in general small cells, with a central, round, highly visible nucleus, surrounded by a thin cytoplasmic ring. Their main morphological characteristic, other than a small size, is their high stainability, regardless of the technique.Lymphatic organs are divided into primary lymphatic (or central) and secondary lymphatic (or peripheral) organs.In humans, primary lymphatic organs are the bone marrow and the thymus (in fetuses, the liver and the spleen). Birds have a particular primary lymphatic organ, located in the intestine, called the bursa of Fabricius. Secondary lymphatic organs are the spleen, lymph nodes, and the mucosa-associated lymphatic tissue (MALT: tonsils, Peyer’s patches, cecal appendix, and other lymphocyte clusters of the mucosa).All the differentiation stages take place in the primary lymphatic organs. Such stages start from already lymphatic-oriented stem cells and produce mature virgin lymphocytes (B lymphocytes in the bone marrow; T lymphocytes in the thymus) (antigen-independent process). After lymphocytes meet the antigen (antigen-dependent activation), they start complying with their functions in the secondary lymphatic organs.There are two main types of lymphocytes:B lymphocytes, are generated and matured in the bone marrow (in birds they generate and mature in the bursa of Fabricius, hence their name);T lymphocytes are generated in the bone marrow, but reach their maturation in the thymus (hence their name).There is a third category of lymphocytes. Initially, they were defined as neither B nor T cells because they do not have the same phenotypic features. They are known as Natural Killer lymphocytes (NK).Once the maturation process is over, lymphocytes migrate towards the secondary or peripheral lymphatic organs, such as the spleen, lymph nodes and the mucosa-associated lymphatic tissue (MALT) in order to comply with their functions and recognize and fight microbial infections. The spleen not only carries out an immune function, but also destroys immature or malfunctioning red blood cells (hemocatheresis). This process takes place in the red pulp.
In humans, this is the main hemopoietic organ. The bone marrow is formed by lymphatic tissue and it is named after its location: the inner cavities of both long and flat bones. In normal conditions, it has a primary function in the production and maturation of blood cells. The bone marrow with hematopoietic function is called red bone marrow because, in vivo, it appears with an intense red color, due to the high presence of blood and erythrocytes.During the first moments of the fetus life, it first appears in the clavicle and subsequently spreads to all the remaining bones. During fetal development and for several years, the red bone marrow is prevalent. After the individual develops, the majority of bone marrow loses its hemopoietic function, while the adipocyte and connective component increases. This involves a change in color, which turns white-yellowish. The result is yellow bone marrow. In adults, this change narrows the hemopoietic function, and hence the presence of red bone marrow, to some zones of the cranial diploë, and to sternum, ribs, iliac crests and the central areas of some short bones.Bone marrow includes:the supportive tissue, formed by connective cells, reticulocytes, that form a dense reticular meshwork with their argyrophilic fibers. Such meshwork supports the cells of the hemopoietic tissue and forms a spongy reticular system that eases their passage and migration;the hemopoietic compartment, packed with differently matured cells (erythrocytes, neutrophil granules, basophilic granules, eosinophilic granules, lymphocytes, monocytes, megakaryocytes, platelets);the vascular compartment, constituted by venous sinuses or sinusoids that allow a constant migration of erythrocytes and other elements through the circulation as well as having a trophic function. Leaning against the sinusoids are the megakaryocytes, large cells that through the budding and detachment of a part of cytoplasm create platelets.It is difficult to obtain bone marrow histological preparations due to the extremely delicate structure of this tissue. After an adequate fixation and decalcification of the bone tissue, microtome sections can be achieved, as well as compression preparations or preparations with tissue fragment smears. The most used techniques are those typically used for blood staining: Em-Eo o May Grumwald-Giemsa.
Figure C108A. Human red bone marrow. The hematopoietic tissue is stained red-purple; adipocytes are colorless since the lipid droplet has been solubilized by solvents. H&E X40
Figure C108B. Human red bone marrow. The hematopoietic tissue is stained red-purple; adipocytes are colorless since the lipid droplet has been solubilized by solvents. H&E X40
Figure C109. Human bone marrow in situ. Longitudinal section of a long bone with inside red bone marrow composed of hematopoietic tissue mixed with adipose tissue. H&E X63
Figure C110A. Human bone marrow in situ at higher magnification. You can clearly see both the endosteum that lines the lamellar bone and some large megakaryocytes inside the hematopoietic tissue. H&E X100
Figure C110B. Human bone marrow in situ at higher magnification. You can clearly see both the endosteum that lines the lamellar bone and some large megakaryocytes inside the hematopoietic tissue. H&E X100
Figure C111. Human bone marrow at high magnification. You can see islets of hematopoietic tissue mixed with adipocytes. In the center of the micrograph, you can see a large cell with a polylobed nucleus: the megakaryocyte (arrow), from which platelets originate by budding cytoplasm portions. H&E X200
Figure C112. Bursa of Fabricius. The bursa of Fabricius is a primary lymphoid organ present only in birds and located in the wall of the intestine. Iron hematoxylin-eosin X12.5
Figure C113A. Bursa of Fabricius. Nonetheless, the bursa of Fabricius has a morphological appearance similar to the thymus; it produces B lymphocytes (the B of B lymphocyte derives from Bursa). Iron hematoxylin-eosin X63
Figure C113B. Bursa of Fabricius. Nonetheless, the bursa of Fabricius has a morphological appearance similar to the thymus, it produces B lymphocytes (the B of B lymphocyte derives from Bursa). Iron hematoxylin-eosin X63
This organ is located in front of the heart large vessels. It is formed by two lobes and morphologically characterized by a thick connective capsule, from which various septa leave and divide the organ into lobules. Each lobule contains a peripheral zone, called cortical, with a more intense color, in which thymocytes are more numerous and separate, and a lighter zone, called medullary, centrally located, where thymocytes are less numerous and where some formations called Hassall’s corpuscles are present. Hassall’s or thymic corpuscles are round formations of around 30-100 µm composed of medullary epithelial cells, keratinized and concentrically arranged. This is the reason why they appear highly colored with basophilic staining methods (for example, in HE with eosin intense pink).The thymus is extremely active during childhood: starting from the teenage years, it regresses and leads to a morphological substitution, with a more gradually confused organization, rich in connective and adipose tissue. In adults, the thymus is represented by a few portions of lymphatic tissue surrounded by connective tissue and adipocytes.
Figure C114A. Human thymus. The thymus is a primary lymphoid organ filled up with cells called thymocytes that subsequently mature into T lymphocytes. The connective tissue capsule sends inward septa that divide the organ into lobules, each one containing an external darker cortex and an inner, less stained, medulla. H&E X10
Figure C114B. Human thymus. The thymus is a primary lymphoid organ filled up with cells called thymocytes that subsequently mature into T lymphocytes. The connective tissue capsule sends inwards septa that divide the organ into lobules, each one containing an external darker cortex and an inner, less stained, medulla. H&E X10
Figure C115. Human thymus at higher magnification. The connective tissue capsule sends inwards septa that divide the organ into lobules, each one containing an external darker cortex and an inner lighter medulla. H&E X40
Figure C116. Human thymus at higher magnification. Digitally processed micrograph. You can see the medulla in light green, the connective septa in dark green and the cortex in deep pink. H&E X40
Figure C117. Human thymus. The thymus is easily identifiable as a lymphoid organ because of the subdivision into lobules, the large amount of lymphocytes organized into a cortex and a medulla and the concentric eosinophilic formations in the center of the medulla and named thymic corpuscles. You can notice the large amount of blood vessels stained pink (arrows). H&E X63
Figure C118. Human thymus. In the medulla, the epithelioreticular cells may have a concentric organization that lead to the formation of corpuscles called thymic corpuscles or Hassal’s corpuscles (arrows). These cells show clear signs of degeneration. H&E X200
Figure C119. Thymus in regression of an adult subject. The thymus morphology, after puberty, progressively change: the lymphoid tissue decreases while adipocytes and connective tissue increase. E&H X40
The spleen is a large lymphatic organ located in the abdominal cavity on the left, under the diaphragm. It is surrounded by a thick connective capsule from which several and thick septa leave. Although they penetrate deeply into the organ, they do not split it into lobules. Rather, they become thinner and thinner until they form a thin reticular meshwork that supports the parenchyma. The spleen has various main functions: it organizes the immune response against blood microbes (lymphopoietic function, white pulp) and destroys malfunctioning or deteriorated erythrocytes (hemocatheretic function, red pulp).The parenchyma of the spleen is divided into red pulp and white pulp with the interposed marginal zone, which presents several arteries and active macrophages.White pulp is characterized by lymphatic nodules, ovoid formations composed of B lymphocytes, and periarterioral sheaths formed by T lymphocytes. The arteriole is generally central with respect to the periarterioral sheath. In histological specimens, the white pulp is easily distinguishable due to its darker shade, both with HE and with other conventional staining methods, because of the high affinity of lymphocytes with acidophilic staining methods.Red pulp is composed of a dense network of sinusoids surrounded by endothelial cells, macrophages and plasma cells, and it is uniformly distributed inside the organ. Under the microscope, this area is easily recognized because of its light color, lower concentration of lymphocytes and higher quantity of loose connective tissue.
Figure C120A. Mouse spleen at low magnification. The spleen is a secondary lymphoid organ. The spleen parenchyma presents a white pulp and a red pulp. The white pulp derives its name from the fact that the lymphoid tissue of the periarteriolar sheets is white whereas the red pulp, that is highly vascularized, is dark red. Mallory-Azan X12.5
Figure C120B. Mouse spleen at low magnification. The spleen is a secondary lymphoid organ. The spleen parenchyma presents a white pulp and a red pulp. The white pulp derives its name from the fact that the lymphoid tissue of the periarteriolar sheets is white whereas the red pulp, that is highly vascularized, is dark red. Mallory-Azan X12.5
Figure C121A. Mouse spleen. In the spleen, a secondary lymphoid organ, is evident the division of the parenchyma in a white pulp, made up of periarteriolar sheets, and a red pulp. H&E X25
Figure C121B. Mouse spleen. In the spleen, a secondary lymphoid organ, is evident the division of the parenchyma in a white pulp, made up of periarteriolar sheets, and a red pulp. H&E X25
Figure C122. Mouse spleen. You can see, stained pink-orange, the connective tissue capsule that projects inwards large connective septa, without dividing the organ into lobules.
Figure C123. Human spleen. Azan three-color process shows the connective tissue capsule, stained light blue, that encloses the organ and the septa that project inwards to support, together with the reticular connective tissue, the parenchyma. Mallory-Azan X40
Figure C124A. Human spleen. Reticular fibers that enclose a lymphoid follicle and the central artery. Bielschosky X100
Figure C124B. Human spleen. Reticular fibers that enclose a lymphoid follicle and the central artery. Bielschosky X100
Figure C125. Human spleen. Secondary lymphoid follicle. The B lymphocytes making up the follicle have been stained with anti-IgG (red), anti-IgM (blue) and anti-IgA (green) antibodies. You can see also some small blood vessels. (Courtesy of Silvia Bruno, Department of Experimental Medicine, University of Genoa).
In normal conditions, lymph nodes are small, ovoid organs distributed along the lymph vessels. The lymph node is surrounded by capsular dense connective tissue that sends septa that later penetrate the lymph node parenchyma for a short distance. Although these septa are clearly visible, they rarely manage to reach the medulla. The parenchyma is composed of lymph cell accumulations supported by a stroma composed of a dense network of reticular connective tissue and divided into three zones: the cortex, packed with B lymphocytes, the paracortex, packed with T lymphocytes, and the medulla, packed with plasma cells.The cortex is the most superficial zone. It is located underneath the connective capsule and is composed of numerous ovoid formations called follicles. When follicles present a constant morphology and a uniform color are called inactive primary follicles, while when they present a clearer central area (germinal center of Fleming) surrounded by a darker area (the mantle), they are known as active secondary follicles.Deeper to the follicle zone is the paracortex, rich in T lymphocytes that are squeezed in order to create a dense network in which follicles are rare.In the center of the lymph node there is the medulla, less colored than the cortex because of the high amount of vessels and connective tissue. Here, lymphocytes are clustered around the medullary cords. They are branched and tend to interconnect. Inside the medulla there is a dense network of reticular fibers that adequately support the loose parenchyma of the lymphatic organ. In normal conditions, the blood vessels of the medulla have a reduced volume and are hardly visible.Lymphocytes penetrate the lymph node through two ways: through the afferent lymph vessels, if present in lymph, or through high endothelial venules (HEV), if present in blood.The lymph penetrates the lymph node through lymph vessels (pre-nodal lymphatic collectors) crossing the capsule. Then, it spills in the subcapsular sinus and crosses the medullary sinuses. Finally, it reaches the lymph vessel (post-nodal lymphatic collector) and leaves the organ through the hilum. The lymph that reaches the lymph node can also directly cross the parenchyma to merge into the post-nodal lymphatic collector. This type of lymph flow through the lymph node allows cells that have absorbed the antigen (e.g. dendritic cells) or free microbes to stop inside the lymph node and enable an immune response.
Figure C126A. Human lymph node. In the cortex of the lymph node, you can see several follicles. In the center of the follicle, there is a lighter zone, the germinal center, rich in B lymphocytes, surrounded by a darker external zone, the mantle, rich in T lymphocytes. H&E X25
Figure C126B. Human lymph node. In the cortex of the lymph node, you can see several follicles. In the center of the follicle, there is a lighter zone, the germinal center, rich in B lymphocytes, surrounded by a darker external zone, the mantle, rich in T lymphocytes. H&E X25
Figure C127. Mouse lymph node. Vital staining with India ink that highlights, in black, the vascular network of the organ. India ink X63
Figure C128. Human lymph node. Cortex of a lymph node cut with a cryostat. You cannot see the medulla because the lymph node was cut on the surface. DAB- Ematossilin X25
Figure C129. Human lymph node at higher magnification. You can see two follicles in the cortex of a lymph node. In the center of the follicle, there is a lighter zone, the germinal center, surrounded by a darker external zone, the mantle. H&E X63
Figure C130. Human lymph node. The medulla is characterized by medullary cords (lighter zones) and by medullary sinuses, stained deep pink. H&E X40
Tonsils, the Peyer”s patches and the vermiform appendix belong to the MALT. The lymphatic nodules present in these formations have an organization and a particular, characteristic stable structure: they are an integrated component of the organs they are immersed in. Moreover, they have no connective capsule to mark their border (except for the palatine tonsil hemicapsule), but present a dense meshwork to support them, in its typical ovoid shape. The mucosa-associated lymphatic tissue is organized in follicles that can be either primary or secondary, depending on the presence of a germinal center. Microscopically, tonsils are characterized, other than for the several follicles, for the presence, on their free margin, of a stratified squamous epithelium, typical of the first section of the digestive system (i.e. the palatine tonsils) or of a pseudostratified ciliated epithelium, typical of the respiratory system (i.e. the pharyngeal tonsils). Deeply inside the epithelium, there is a subepithelial zone, interposed between the epithelium and the follicles. Conversely, the vermiform appendix is characterized by a group of lymphatic follicles surrounding a lumen, an extension of the intestinal lumen, covered by a columnar epithelium and by the presence of simple tubular glands.Moreover, all connective tissues, especially the loose ones underneath the epithelia, may contain accumulation of lymphocytes at different developmental stages. Such accumulations are recognizable due to the presence of small, highly colored cells, the lymphocytes, and their volume can vary significantly depending on the level of inflammation of the tissue. These accumulations neither present follicles nor stromal architecture nor, in general, a specific spatial organization.
Figure C131A. Human palatine tonsil. Low magnification micrograph of a palatine tonsil where you can see, under a stratified squamous epithelium, the lymphoid tissue organized into follicles. The presence of stratified squamous epithelium let us to distinguish the palatine tonsils from the pharyngeal tonsils. H&E X12.5
Figure C131B. Human palatine tonsil. Low magnification micrograph of a palatine tonsil where you can see, under a stratified squamous epithelium, the lymphoid tissue organized into follicles. The presence of stratified squamous epithelium let us to distinguish the palatine tonsils from the pharyngeal tonsils. H&E X12.5
Figure C132. Human lingual tonsil. Lingual tonsil where you can see, under a stratified squamous epithelium, the lymphoid tissue organized into follicles. Mallory-Azan X25
Figure C133. Human lingual tonsil. Digitally processed micrograph to highlight the lymphatic nodules. X25
Figure C134. Human palatine tonsil. Under the stratified squamous epithelium, you can see three lymphatic nodules, each with a germinal center in the middle. H&E X40
Figure C135. Human pharyngeal tonsil. You can distinguish the pharyngeal tonsil from the palatine and lingual tonsils because the tissue is lined by a ciliated pseudostratified epithelium, typical of the rhinopharynx. H&E X40
Figure C136. Human pharyngeal tonsil. Human pharyngeal tonsil at higher magnification to highlight the ciliated pseudostratified epithelium of the rhinopharynx. H&E X200
Figure C137A. Human vermiform appendix. Transverse section. This low magnification micrograph allows to esteem the organization of the appendix. H&E X12.5
Figure C137B. Human vermiform appendix. Transverse section. This low magnification micrograph allows to esteem the organization of the appendix. H&E X12.5
Figure C138A. Human vermiform appendix. You can see the intestinal glands, the simple columnar epithelium with goblet cells and a lymphatic follicle. H&E X40
Figure C138B. Human vermiform appendix. You can see the intestinal glands, the simple columnar epithelium with goblet cells and a lymphatic follicle. H&E X40
Figure C139. Human colon. Lymphatic nodules, transverse section. H&E X40
Figure C140. Human colon. Lymphatic nodules, transverse section. H&E X100
In pathologic conditions, it is possible to highlight the presence of lymphocytic infiltration caused by inflammatory reaction inside the organs.
Figure C141A. Human skin. Lymphocyte infiltrate in a patient with lupus erythematosus sistemicus. Alcian Blue-Ematossilin X100
Figure C141B. Human skin. Lymphocyte infiltrate in a patient with lupus erythematosus sistemicus. Alcian Blue-Ematossilin X100
Figure C142. Human skin. Lymphocyte infiltrate in the dermis of a patient with psoriasis. Alcian Blue-Ematossilin X100
Figure C143. Dolphin lung at high magnification. Lymphocyte infiltrate and macrophages in a lung infection. Both lymphocytes and macrophages (arrows) are positive for the protein Bcl-2 (brown precipitate), a protein that promotes cell surviving by inhibiting apoptosis.
Figure C145. Mouse kidney. Strong lymphocyte infiltrate in the cortical zone and, in particular, in the glomeruli. H&E X40
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