IMMUNE AND HEMOPOIETIC ORGANS
1. Hemopoietic organs classification.
2. Сommon features of hemopoietic organs
3. Red bone marrow
4. Yellow and mucous bone marrow
5. Thymus
6. Thymus involution
7. Spleen
8. Lymph nodes
In human body there are special structures, which prove the homeostasis of blood and immune system, they are the organs of hematopoiesis and immune protection. Such organs belong to this system: red bone marrow, thymus, spleen, lymph nodes, and lymph nodules (mucosa-associated lymphoid tissue of tonsil’s, intestine, respiratory system).
General features of hematopoietic organs.
1. Origin – mesenchyme
2. Structure
a. Stroma
Reticular tissue
Sinusoids
Macrophages
b. Parenchyma
Myeloid tissue
Lymphoid tissue
3. Functions
a. Hematopoiesis
b. Deposition of blood
c. Protective
d. Elimination
There are central and peripheral organs. Red bone marrow and thymus are the central ones. Erythrocytes, platelets, granulocytes and lymphocytes precursors take their origin in the red bone marrow. Thymus is the central lymphopoietic organ. It is necessary to underline that lymphocytes antigenindipendent prolipheration takes place in the central hematopoietic organs. Antigendependent proliferation of lymphocytes occurs in the peripheral hematopoietic organs, which lead to appearance of active special cells and memory cells. Besides the old and destroying cells are finishing their life span there.
All the hematopoietic organs are functioning simultaneously and prove the constant compounds of the blood and immune homeostasis. Coordination and regulation of their functions is performed by the humoral and nerve influences.
Despite on structural differences of hematopoietic organs, all of them have the similar morphofunctional signs. First of all reticular tissue (connective tissue with special properties) form their stroma and create the special microenvironment to the developing hemopoietic cells and lymphocytes. Their capillaries (sinusoids in red bone marrow and fenestrated on other organs) have the electoral permeability to the mature cells. Thanks to the numerous phagocyzing cells (macrophages of different types) and immune cells hematopoietic organs have protectory function, they can purify the blood or lymph from foreign particles, bacteria and remnant of dead cells.
Bone marrow (medulla osseum)
Bone Marrow– is the central hematopoietic organ, which contain the population of self-supporting stem cells and produces both cells types –myeloid and lymphoid.
In adult human being bone marrow is one of the large organs of the body and the main site of hematopoiesis. Under normal conditions, the production of blood cells by the marrow is perfectly adjusted to the organism’s functions. It can adjust rapidly to the body’s needs, increasing its activity several fold in a very short time if required. Bone marrow is found in the medullar canals of long bones and in the cavities of spongious bones. Two types have been described according to their appearance on gross examination: red, or hematogenous, whose color is due to the presence of blood and blood-forming cells, and yellow bone marrow, whose color is due to the presence of a great number of adipose cells.
RED BONE MARROW (medulla osseum rubra)
Red bone marrow is the hemopoietic portion of the bone marrow. It is the semifluid organ of dark red colour. This allows preparing the red bone marrow smear for investigation, which may be stained likes a blood smear with Romanovsky-Himsa method.
Red bone marrow is composed of a stroma (from Greek, bed), parenchyma of hematopoietic cords and sinusoidal capillaries. The stroma is a 3-dimensional meshwork of reticular cells with phagocytotic properties and a delicate web of reticular fibers containing hematopoietic cells and macrophages. Reticular cells have extensive branched cytoplasmic processes, which enclose well over 50 % of the outer surface area of the sinusoid wall. It is the reticular cells, which also ramify throughout the hemopoietic spaces forming a regular sponge-like matrix, a meshwork to support the hemopoietic cells, they also produce special growth factors, which influence on the hematopoiesis.
The sinusoids in red bone marrow are formed by endothelial cells with fenestrae and discontinuous basement membrane. Fenestrated thin regions of the endothelium are the sites for migration of mature cells from the stroma into the sinusoids. Endothelial cells are capable for contractile movement, which helps to blood cells exfusion from the red bone marrow parenchyma into the capillaries blood stream. After the cells passage fenestrae are closed. Endotheliocytes produce colony-stimulying factors and fibronectin, special protein antigen properties, which ensures cells adhesion one to each other and with substratum.
Some others cells are concerned to the hemopoietic cells microenvironment.
Stromal cells of hematopoietic organs
1. Reticular cells
2. Osteogenic cells
3. Adipocytes
4. Adventitial cells
5. Endothelial cells
6. Macrophages
Parenchyma of hemopoietic organs may consist of different blood cells myeloid type or lymphocytes – lymphoid parenchyma.
By accumulating lipids, the reticular support cells may transform into the adipocytes. Thus such cells are the constant compounds of the red bone marrow. They are oval-shaped and contain large vacuole of the lipid inclusions; their flattened nuclei are disposed peripherally under the cell membrane.
Group of osteogenic cells includes the stem cells of the supporting tissues like’s osteoblasts and their precursor cells. Osteogenic cells are disposed in the endosteum and may be found in the bone marrow spaces. These cells are capable to produce growth factors and to stimuli the blood stem cells to proliferation and differentiation in their site. Thus the most active hematopoietic processes take place near the endosteum, where the amount of stem cells are three times numerous then inside in the middle of bone marrow space.
Adventitial cells are the frequent cells of blood vessels wall, very often they cower the sinusoids from outside. They may contract under the influence of some hemopoietic factors (for example, erythropoietin). Thus they promote cells migration into the blood stream.
Inhomogeneous cells, which are a little bit differ in structure and functional possibilities, present macrophages in the red bone marrow but all of them are reach in lisosomes and phagosomes. Some of macrophages populations are secreting biologic active substances (erythropoietin, colony stimulying factor, interleukins, prostaglandins, interferon and others). By means of their processes, macrophages can introduce into blood stream through the capillaries wall and extract ironcontaining substance transferrin from the blood, and transfer it to the maturing erythroid cells. This matter is utilized for the hemoglobin gemin construction.
Red bone marrow parenchyma consists of hematopoietic cells differons, which are organized into four principle groups or hematopoietic islets: erythropoietic, granulocytopoietic, agranulocytopoietic and poiesis of platelets.
Erythropoiesis is tightly connected with macrophages. Red cells are formed in small erythroblastic islet. Such islet consists of one or two specialized phagocyte surrounded by red progenitor cells, which arise from colony forming unite that touch in contact with bone marrow macrophage. The macrophages have long cytoplasmic processes and deep invaginations to accommodate the dividing erythroid cells. All these cells are combined with him by his receptors – syaloadhesins.
Macrophages “feed” erythroblasts with iron and some compounds for ferritin. They also remove the nuclei of erythroblasts, which are exfused during their maturation. Erythroid cells migrate outwards along the macrophages cytoplasmic processes. When mature, the red cells contact nearby sinusoidal endothelium, separate from islets and pass out to enter the circulation through the capillaries wall, which consists of fenestrated endothelial cells. There are a lot of fixed macrophages among the endothelial cells. Numerous phagocytes that are present in blood islets and capillaries wall allow controlling the maturation of erythrocytes and their passage into the blood stream.
Granulopoiesis includes the formation of granulated cells. This takes place under the influence of cytokines. Granulocytopoietic cells are organized into islets, which lie in the periphery of the bone medullar cavity. Nonmature cells are surrounded with proteoglycans, which are necessary to their normal development. Maturing granulocytes are stored in the red bone marrow; there are three times more granulocytes then erythrocytes here, and 20 times more granulocytes in the red bone marrow than in the peripheral blood.
Megakaryoblasts and megakaryocytes huge multinuclear cells are disposed near the capillaries wall in such way that their pseudopodia introduce through the wall pores into the blood. Platelets are formed by separation of cytoplasm portions (by demarcation membranes) directly into the blood stream.
Myeloid tissue of red bone marrow includes small group of bone marrow lymphocytes and macrophages, which surround the blood capillary. Monocytes leave the marrow after formation with no marrow pool. They spend about 3 days in the blood before migration into the tissues in an apparently random fashion; they are then unable to re-enter the circulation.
The bone marrow is the site of formation of primitive lymphocyte precursors, which subsequently give rise to both T- and B-lymphocytes at different sites. B cells undergo initial maturation in bone marrow and move on to colonize peripheral lymphoid tissues. T cells migrate to the thymus gland where they undergo initial maturation before moving on to colonize peripheral lymphoid tissues. Lymphoid cells are capable of division in adult life, when expansion of selected clones is desirable to mount a specific immune response.
YELLOW BONE MARROW (medulla osseum flava)
Iewborns, all bone marrow is red and is therefore active in the production of blood cells. As the child grows, most of the bone marrow changes gradually into the yellow variety in the diaphysis of tubular bones. It has yellowish colour due to the presence of numerous adipocytes with pigment likes lipochromes.
As a rule iormal condition yellow bone marrow has no hematopoietic function but under certain conditions, such as severe bleeding or hypoxia, yellow bone marrow converts back into red bone marrow and myelopoietic islets appear from the bringing stem and hemistem cells.
There is no distinct difference between the yellow and red bone marrow. Some adipocytes may be observed in the red bone marrow constantly. Correlation between red and yellow bone marrow is changed in accordance with age, feed, nerve and endocrine regulation.
Bone marrow blod supplying. Red bone marrow possesses its blood supplying from the nutritive vessels, which introduce through the periosteum into the special opening in the compact bone.
Innervation. Bone marrow is innervated from the nearest blood vessels plexuses, muscular nerves and special nerves to the bone marrow. Nerves enter the bone marrow with the blood vessels through the bones channels. Then they leave vessels and proceeded with independent branches into the medullar parenchyma of the spongy bone. They are ramifying into thin fibers, which touch to the walls of bone marrow vessels or lye free among the bone marrow cells.
Age changes. In the childhood red bone marrow fulfills epiphyses and diaphyses of tubular bones and in the lamellar bones. At about 12–18 years red bone marrow is transformed into yellow one in the diaphyses. In the old age bone marrow (both red and yellow) has a mucous constituency and is called gelatinous bone marrow. It is necessary to say, that this type of bone marrow may be found somewhere early (for example, in the developing bones of skull and face).
Regeneration. Red bone marrow has well prominent physiologic regeneration and good capability for reparative one. Stem cells in tight connection with reticular stroma are the source of hemopoietic cells formation. The speed of the red bone marrow regeneration much depends on the microenvironment and growth stimulating factors of hematopoiesis.
THYMUS (thymus)
In man the thymus or thymic gland is the central immune and lymphocytopoietic organ. It proves antigenindipendent differentiation of T-lymphocytes from their precursors. During this process, the immune system distinguishes self from foreign antigens and develops self-tolerance.
It is an unpaired organ situated in the anterior mediastinum, in close connection with the pericardium and the great veins at the base of the heart. The thymus presents marked variations in its structure, depending on the age and on the condition of the organism as a whole. The organ is closed related lo lymphatic tissue; it produces lymphocytes and occasional lymphatic nodules develop within it. Other functions of this organ are the next: regulation of T-lymphocytes proliferation in the peripheral organs by means of thymosin production and their selection. Thymus also performs endocrine function, producing such hormones as: insulinlike factor, which decrease the sugar level in the blood, calcitoninlike factor, which decrease the calcium level and growth factor.
In relation to body weight, the thymus is largest during embryonic life and in childhood up to the period of puberty. At birth the thymus weighs 12 to 15 gm. This increases to about 30 to 40 gm at puberty, after puberty the thymus begins to decrease in weight, so that at sixty years it weighs only 10 to 15 gm.
Structure. The thymus consists of two main lobes, one on each side of the median line, which is closely joined by connective tissue, but is not actually fused. Each of these lobes is divided into a number of macroscopic lobules varying from 0.5 to 2 mm in diameter. The lobules are separated from one another by the interlobular connective tissue and are divided into a darkly staining, peripheral cortical area and a lighter staining, inner medullary portion. The difference between the cortex and medulla is the fact that the cortex consists mainly of densely parked small lymphocytes with their dark nuclei and, in between them, only a relatively few reticular cells, with pale-staining nuclei. In the medulla it is the reverse. From the cortex toward the medulla, the number of lymphocytes drops rather abruptly, but there is no sharp line of demarcation between the two zones. The medulla is more vascular that the cortex.
As parenchymatous organ the thymus consists of the stroma and parenchyma. The stromal reticular cells are elongated and have pale, round or oval nuclei. In most cases they contain predominantly euchromatin and one or two nucleoli. In the cortex it is difficult to follow the outlines of their cytoplasm, since the surrounding lymphocytes (thymocytes) are closely packed around them. In the medulla the lymphocytes are less numerous and it can be seen that the reticular cells form a network with its meshes filled with lymphocytes.
Different types of epithelioreticulocytes may be recognized due to their disposition, size, shape, hyaloplasm density, amount of organelles and inclusions. There are secretory cortical and medullary cells, nonsecretory (supporting) cells, and cells of Hassall’s body.
Secretory cells contain vacuoles and secretory inclusions, which are composed of hormone-like factors: a-thymosin, thymulin, thymiopoietins. In subcapsular zone and outer cortex lymphocytes are rested in deep invaginations of epithelial cells. As a rule from 10 to 20 thymocytes may be disposed in such nurse-cell, thus cytoplasmic layer between them are very thin. Lymphocytes may “exfuse” and enter the invaginations and form the tight contacts with stromal cells.
The other types of supporting cells in the cortex are macrophages: typical free and their derivatives – dendrite cells.
The lymphocytes of the thymus are morphologically identical with the small lymphocytes in the lymph node and other lymphatic tissues. Some of them are identical with medium-sized and large lymphocytes. Thymocytes arise from the mesenchyme in red bone marrow, and are lymphocytes, which have wandered into the epithelium. Small T-lymphocytes are disposed more peripherally, while lymphoblasts occupy the subcapsular zone of the cortex. Clones of T cells are produced by cell division in the outer part of the thymic cortex and undergo maturation as they are pushed deep into the cortex toward the medulla.
In the medulla, the maturing T cells enter blood vessels and lymphatics to join the pool of circulating T cells. They subsequently populate peripheral lymphoid tissues, where they reach full immunologic maturity. The amount of the cells is much more less then in cortical zone of the lobule. Cell divisions are seen very rare (15 times less then in cortex). Only a small minority of lymphocytes generated in the thymus are believed to reach maturity. These are clones of T cells with the ability to recognize foreign antigens.
The rest of the lymphocytes are thought to recognize self antigens and are eliminated: this results in immunologic self-tolerance.
Hassall’s bodies. The medulla contains the bodies of Hassall, which are characteristic of the thymus. They are rounded mild acidophilic structures, which vary from 30 to 100 microns in diameter. They are composed of concentrically arranged cells, many of which show evidences of degeneration and hyalinization. Reticular cells are connected at one or more places with the periphery of each Hassall body. The cells of the central part of Hassall body may degenerate completely, so that small cysts may develop in the center. In other cases calcium may be deposited in them.
Involution of the thymus. The thymus reaches its maximum weight at puberty after which it begins to involute —a process, which proceeds gradually and continuously throughout life under normal conditions. It is declining so that in old age it may be so small as to be unrecognizable. This change in its structure is spoken of as age involution. During the course of infectious and cachectic diseases the normal slow involution may be greatly accelerated. This is called accidental involution, and explains many of the contradictory reports on the size of the thymus, since the organ did not have a chance to regenerate in those persons who died as a result of severe infection.
Despite the progressive decrease in their number with involution, thymic lymphocytes continue to differentiate and proliferate, thus maintaining a supply of T cells throughout life.
The last elements to be replaced are the Hassall bodies, but even in very old persons there are scattered Hassall bodies surrounded by a few reticular cells and lymphocytes. This process of normal or age involution may be complicated by the rapid changes of “accidental involution”. Histological picture of the thymus are similar to the above mentioned age involution but it is connected with rapid exfusion of T lymphocytes into the blood stream and their mass destruction inside in the thymus especially in the cortical zone. At the same time epitheliocyte are enlarged. Their cytoplasm contains numerous droplets, which are glycoproteid-positive. Sometimes these inclusions are organized into follicular structures between the cells.
The thymus is functionally tightly interconnected with adrenal gland. The increase of the adrenal cortex hormones, especially glucocorticoids, may produce very active and well prominent accidental involution of the thymus.
But sometimes, age involution of the thymus does not occur. Such situation is known as “status thymico-lymphaticus”, it is the evidence of serious problem of adrenal cortex deficiency. In such men there is enlarged lymphoid tissue: enlarged lymph nodes and even in adult well prominent thymus but there are no enough hormones of adrenal glands. They are very sensitive to different influences from outside and require a special attention of medical stuff.
Vessels and nerves. The thymus has a reach vascular supply, which allows migration of lymphoid cells. The arteries supplying the thymus arise from the internal thoracic and the inferior thyroid arteries and are first distributed to the cortical tissue via the interlobular septa.
In the region of the corticomedullary junction the vessels give rise to small radially arranged arterioles and capillary loops to supply the cortex and medulla. The cortical capillaries have continuous endothelium, whereas those of the medulla and septa are of fenestrated type. Continuous basement membrane and a layer of epithelial cells, which border pericapillary space, surround cortical capillaries. In this space a lot of macrophages and some lymphocytes are observed. All this structures are named “the hematothymical barrier”. It includes the wall of hemocapillary, which consists of endothelial cells and continuous basement membrane, pericapillary space with lymphocytes, macrophages and intercellular substance and epithelioreticular cells with their basement membrane. This barrier has selective permeability as for the antigens. It preserves the lymphocytes from antigens influence and thus promotes their antigen independent prolipheration. In the case of barrier been damaged isolated plasma cells, granular leucocytes and must cells are observed. Sometimes foci of extramedullary myelopoiesis appear in the cortex.
At the corticomedullary junction, which is the site of lymphocyte migration into the thymus, postcapillary venules have a taller endothelium with features of high endothelial venules. Lymphocytes of this zone may migrate out of thymus and return back (recirculate).
Venous tributaries follow the course of the arterial vessels in the septa, some forming a plexus within the thymic capsule before draining via the thymic veins into the left brachiocephalic, internal thoracic and inferior thyroid veins.
Thus, the blood drainage from thymic lobules cortex and medulla is separating.
The thymus receives no afferent lymphatics. But the medulla and corticomedullary area give rise to efferent lymphatics.
The thymus receives a few branches from the vagus and sympathetic nerves; these are probably mainly of vasomotor nature.
Thymus functions. As a central hematopoietic organ thymus is responsible for the antigenindependent proliferation of T lymphocytes, it also participates in the lymphocytes selection and regulates their proliferation and differentiation in the peripheral hematopoietic organs by means of hormone thymosin.
The change from a large organ during embryonic development, infancy, and childhood, into a gradually disappearing organ with the development of sexual maturity, has led many authors to ascribe an endocrine function to this gland.
This function includes thymosin production and synthesis of some others biologically active factors as insulinlike factor, which decrease the sugar level in the blood, calcitoninlike factor, which decrease the calcium concentration in the blood and growth factor.
LYMPH NODES
Lymph nodes are encapsulated round or kidney-shaped organs composed of lymphoid tissue. They are distributed throughout the body, always along the course of the lymphatic vessels, which transport lymph into the thoracic and the right lymphatic ducts. They are found in the axillas and in the groin, along the great vessels of the neck, and in large numbers, in the thorax, the abdomen, and especially in the mesentery.
Lymph node has both convex and concave surfaces. The parenchyma (lymphoid tissue) consists of a peripheral cortex, adjacent to the convex surface, and a central medulla lying near the depression (hilum) in the concave surface. The connective tissue capsule that covers the node’s surface gives off trabeculae that penetrate between the cortical nodules and subdivide the cortex. Blood vessels enter and leave through the hilum.
Cortex in active lymph nodes, the cortex is dark-staining because of the presence of tightly packed lymphocytes. These are suspended in a reticular connective tissue network and arranged as a layer of typical secondary lymphoid nodules (containing primarily В lymphocytes) with germinal centers. The cortex also contains reticular cells, antigen-presenting follicular dendritic ceils, a few plasma cells, and some helper T cells. Secondary lymphoid nodules are covered by an incomplete lining of reticuloendothelial cells. These cells combined structure of reticular cells with function of epithelial cells, because they cover sinuses of the lymph nodes. Bach germinal center contains В lymphoblasts and it is light, here is proliferation of lymphocytes. In dark peripheral portion of the germinal center there are a lot of small and middle-sized lymphocytes.
Medulla lighter staining than the cortex, the medulla is composed of cords of lymphoid tissue (medullary cords). The В lymphocytes are mainly small, less numerous than in the cortex, and concentrated in the cords. The cords are also rich in macrophages and contain many plasma cells that have migrated from the cortex. Medullary cords are covered by reticuloendothelial cells as secondary lymphoid nodules in the cortex. Pale medullary sinuses surrounding darker medullary cords. You can see many stellate reticular cells which, with reticular fibers, make a meshwork through the sinuses. Lymph “percolates” through the meshes of the sinuses while debris of foreign matter in it is phagocytized. Lymph nodes thus act as filters for the connective tissue fluid compartment of the body.
Paracortical zone. This is the T-dependent region, lying between the cortical lymphoid nodules and the medulla. It is poorly defined morphologically but functionally distinct. It contains mainly T-lymphocytes suspended in a reticular connective tissue network. В lymphocytes, plasma cells, and antigen-presenting interdigitating cells may also be present. Antigen-presenting interdigitating cells connected together by their processes and produce substances which stimulate the proliferation of T lymphocytes.
This zone is also characterized by the presence of many high-endothelial postcapillary venules. T lymphocytes leave the blood to enter the paracortical zone by passing between the cuboidal endothelial cells of these vessels.
Lymphatic vessels associated with lymph nodes are of 2 types. Both contain valves to ensure a unidirectional flow of lymph through the node. Afferent lymphatic vessels deliver lymph by penetrating the capsule at several points on the node’s convex surface. Efferent lymphatic vessels carry filtered lymph away from the node, exiting through the hilum on the concave surface.
Sinuses. The lymphatic sinuses are the spaces incompletely lined by reticuloendothelial cells. The sinuses of the lymph nodes filter the lymph passing through them and direct its flow. Partly lined by reticular cells and many macrophages, they are not simply open spaces, but are traversed by a meshwork of reticular cells and fibers, macrophages, and follicular dendritic cells. The complex seiving action slows lymph flow to facilitate the removal of antigens. Lymph is delivered by the afferent vessels to the cuplike subcapsular sinus between the capsule and cortical secondary nodules. From here it passes directly into the peritrabecular sinuses on either side of the trabeculae. It then flows through the anastomotic network of medullary sinuses which are between medullary cords that converge on the efferent lymphatic vessels exiting through the hilum.
SPLEEN
The spleen is the largest accumulation of lymphatic tissue in the organism, and in humans it is the largest lymphatic organ in the circulatory system. It is a visceral organ lying between the gastric fundus and the diaphragm. The spleen is 12 cm long, 7 cm wide, and 4 cm thick and weighs 100-150 g in a healthy adult.
The largest lymphoid organ, spleen’s functions include lymphopoiesis, immunoglobulin production, and filtering the blood for cellular debris and antigens. Because it serves as the immunologic filter of the blood, its blood supply and circulation are especially important. The spleen is encapsulated in a dense irregular connective tissue capsule covered by mesothelium. Unlike other lymphoid organs, the spleen lacks a definitive cortex and medulla. The parenchyma (splenic pulp) lacks true lobules; however, the dense connective tissue capsule gives rise to trabeculae that divide the splenic pulp into incomplete compartments (white and red pulp). The cornective tissue of the capsule and of the trabeculae contains some smooth muscle cells. In humans, these cells are not numerous. In certain other mammals (cat, dog, horse) they are quite abundant, and their contraction causes the expulsion of accumulated blood from the spleen, which has a spongy structure and serves to store blood cells.
Splenic pulp is composed of many erythrocytes, leukocytes and macrophages, as well as a variety of blood vessels, all suspended within a supporting meshwork of reticular cells and fibers, the main function of which is of support. Unstained slide of splenic pulp exhibit numerous whitish islands of lymphoid tissue (white pulp) embedded in a sea of dark red erythrocyte-rich tissue (red pulp).
White pulp (20 %) is composed of collections of lymphocytes similar to the primary and secondary nodules of lymph nodes. These nodules are surrounded by reticuloendothelial cells. These nodules are easily distinguished from other nodules encountered in the various lymphatic organs because of the presence of the central artery. Nodules of the spleen white pulp have four major components: 1 well-formed germinal centers; 2. periarterial lymphatic sheaths; 3. peripheral white pulp; 4. marginal zone.
Germinal centers have the same structure and functions as lymphatic nodules of the lymph nodes. They contain В lymphoblasts, dendritic and reticular cells. The appearence of germinal centers is the reaction for antigen stimulation.
The sleeves of lymphoid tissue immediately surrounding each central artery called periarterial lymphatic sheaths (PALS). These contain mainly T lympho-cytes and constitute the thymus -dependent zones of the spleen. Surrounding each PALS or appended to one of its sides is the third component, the marginal zone.
Marginal zone Forming the border between white and red pulp, this zone consists of a moatlike arrangement of blood sinuses and loose lymphoid tissue containing few T and В lymphocytes, but with many macrophages, having branching processes and showing active pfagocytosis. The marginal zone retains great amounts of blood antigens and thus plays a major role in the imrnulogic activity of the spleen. Many of the pulp arterioles, derived from a central vein, extend out and away from the white pulp but then turn back and empty into the moatlike sinuses of the marginal zone that encircles the nodules. As a consequence of this drainage, which includes the added blood flow from vessles within the white pulp that also terminate in the marginal zone, this area plays a significant role in filtering the blood and launching an immune response. A large number of macrophages end reticuloendothelial cells serve to phagocytose and remove antigenic debris. Dendritic cells in the marginal zone trap and present antigens to immunologically competent cells. The marginal zone is an idea! site for this activity since not only the antigens are removed from the blood here but also the T and В lymphocytes. All these lymphocytes leave the systemic circulation to penetrate the white pulp, they pass by the dendritic cells, presenting exposed antigen. If the appropriate В cells. T ceils, and antigen are present, an immune response will be initiated. Activated В cells migrate to the center of the v/hite pulp nodule, the germinal center, and give rise to immunoblasts, plasma cells, and activated В cells. The latter 2 cells enter the red pulp, where the plasma cells remain in the cords and release antibody into the blood of the sinuses. Activated В cells leave the red pulp and return to the general circulation.
The lymphocytes of the periarterial lymphatic sheaths are thymus-depended, whereas the marginal zones and periphery of the nodules – the peripheral white pulp – are populated by В lymphocytes. Thus, the splenic white pulp has В and T lymphocytes segregated in 2 different sites.
The splenic reticulum (stroma). Reticular cells and reticular fibers similar to those in lymph nodes exist throughout much of the parenchyma of the spleen. These cells and fibers form a scaffolding that supports both red and white pulp of the spleen. Reticular cells and fibers around central arteries are arranged in concentric layers (as opposed to a sponge mesh) to support the PALS.
Red pulp (80 %) is composed of elongated structures, the splenic red pulp cords which lie between the splenic sinusoids. Red pulp cords (Billroth’s cords; are irregular sheets of reticular connective tissue, these cords branch and anastomose to surround the sinuses. They vary in thickness according to the distention of the adjacent sinusoids. In addition to reticular cells and fibers, the cores contain many cell types, including all the formed elements of blood (erythrocytes, platelets, and granulocytes), dendritic cells, macrophages, plasma cells, and lymphocytes.
Splenic sinuses are peculiar vascular channels, which are lined by tapered cells elongated parallel to the long axis of the sinus. These cells contain many contractile microfilaments and lack attachment specializations between them. Fixed macrophages between them are known to be macrophages (waterside cells). The splenic sinuses are surrounded by a fenestrated basement membrane and by adventitial reticular cells that comprise part of the splenic cords. Blood cells in the splenic cords pass through the wall of a splenic sinus between the lining cells, into the lumen of the splenic sinus, and then out of the spleen through the splenic veins.
Splenic sinusoids. These differ from common capillaries in 3 ways: 1. they have a dilated, large irregular lumen; 2. between their lining endothelial cells are spaces that facilitate exchange between the sinusoids and lying tissues; 3. the basement membrane-like material is not continuous but forms barrel hooplike rings around the endothelial walls.
The endothelial cells that line the splenic sinusoids are elongated, with their long axis parallel tj the sinusoids. These cells are enveloped in reticular fibers set mainly in a transverse direction, similar to the loops of a barrel. The transverse fibers and those oriented in various directions join to form a network enveloping the sinusiod cells. It was formerly thought that the endothelial cells of sinuses were phagocytic; however, it appears that the observed phagocytosis was due to processes of macrophages that has penetrated into the spaces between adjacent endothelial cells. The spaces between the cells of the splenic sinusoids can be 2- 3 μm in diameter or even larger, so that erythrocytes are able to pass easily from the lumen of the sinusoids to the red pulp cords.
The slitlike spaces between the endothelial cells permit extensive exchange of fluids, solutes, and flexible cells between the sinusoids and cords. Macrophages in the cords extend their processes through the slits and phagocytose material in the sinusoid lumen.
Splenic circulation. Arterial supply. The spleen receives blood from the splenic artery (a branch of the celiac trunk of the aorta). Near the hilum, the splenic artery branches into a series of trabecular arteries. These enter the spleen through the trabeculae and branch to enter the parenchyma as the numerous central arteries around which the white pulp is organized. After passing through the white pulp, the arteries give rise to many penicilar arterioles, which in turn give rise to many capillaries and sheathed arterioles. Near their termination, the sheathed arterioles have localized wall thickenings that consist of macrophages. Many of the capillaries arising from the central artery loop back toward the white pulp to feed the marginal sinuses. Others, including those arising from the penicilar and sheathed arterioles, are. the sinusoids of the red pulp.
Open and closed theories of splenic circulation. The way in which blood in the splenic capillaries reaches the sinusoid lumens is not clear. The closed theory of circulation holds that the capillary walls are continuous with the walls of the sinusoids and the capillaries empty directly into the sinusoid lumens. The open theory holds that the capillaries end abruptly in the red pulp cords and that blood reaches the sinusoid lumens by percolating through the cords and passing through openings in the sinusoid walls. For humans, current evidence favors the open theory.
Venous drainage from the sinusoids, blood flows into red pulp veins that converge on the trabeculae and empty into trabecular veins; these are unusual in that walls lack a distinct tunica media. The trabecular veins exit the spleen through the hilum, emptying into the splenic vein, which joins the inferior mesenteric vein and empties into the hepatic portal vein just before it enters the liver.
Functions of the spleen. 1. Elimination of old and abnormal blood cells (e.x.) erythrocytes. 2. Hemopoiesis (formation of lymphocytes in adult, all blood cells in embryo).3. Immune defence of organism against foreign particles that enter the bloodstream. 4. Storage of the blood.5. Endocrine (splenin synthesis).
References:
A-Basic:
1. Practical classes materials:http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/English/medical/III%20term/15%20Immune%20and%20hemopoietic%20organs.htm
2. Lecture presentations: http://intranet.tdmu.edu.ua/ukr/kafedra/index.php?kafid=hist&lengid=eng&fakultid=m&kurs=2&discid=Histology,%20cytology%20and%20embryology
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4. Wheter’s Functional Histology: A Text and Colour Atlas / [Young B., Lowe J., Stevens A., Heath J.]. – Elsevier Limited, 2006. – P. 207-234.
5. Singh I. Textbook of Human Histology with colour atlas / I. Singh. – [fourth edition]. – Jaypee Brothers Medical Publishers (P) LTD, 2002. – P. 178-192.
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B – Additional:
1. Eroschenko V.P. Atlas of Histology with functional correlations / Eroschenko V.P. [tenth edition]. – Lippincott Williams and Wilkins, 2008. – P. 191-211.
2. Junqueira L. Basic Histology / L. Junqueira, J. Carneiro, R. Kelley. – [seventh edition]. – Norwalk, Connecticut : Appleton and Lange, 1992. – P.285-306.
3. Charts: http://intranet.tdmu.edu.ua/index.php?dir_name=kafedra&file_name=tl_34.php#inf3
4. Disk: http://intranet.tdmu.edu.ua/data/teacher/video/hist/
5. Volkov K. S. Ultrastructure of cells and tissues – Ternopil : Ukrmedknyha, 1999. – P. 40-47. http://217.196.164.19/data/books/Volkov(atlas).pdf
6. http://en.wikipedia.org/wiki/Immune
7. http://en.wikipedia.org/wiki/Immune-system
8. http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
9. http://www.udel.edu/biology/Wags/histopage/histopage.htm
