Lesson 18 - Lymphoid Organs III (notes) PDF

_____________ LESSON 18 _____________ LYMPHOID ÓRGANS (III) Secondary Lymphoid Organs: Spleen I. INTRODUCTIÓN The spleen is a secondary lymphoid organ interposed in the blood circulation, which has four major functions: A. Haematopoietic function, or the process of formation and maturation of red b...

_____________ LESSON 18 _____________ LYMPHOID ÓRGANS (III) Secondary Lymphoid Organs: Spleen I. INTRODUCTIÓN The spleen is a secondary lymphoid organ interposed in the blood circulation, which has four major functions: A. Haematopoietic function, or the process of formation and maturation of red blood cells. However, in disease states, leukocytes, erythrocytes, megakaryocytes, and platelets can be also produced. B. Haemocatheretic function, or the process of physiological and controlled destruction of blood cells. With this function, the spleen acts as a blood filter, engulfing cells such as old or bad red blood cells, leukocytes and platelets. C. Immune function, as a secondary lymphoid organ, B and T cells are stimulated in by antigens to give rise to humoral and cellular immune responses, respectively. D. Mechanical function. In a normal state, the spleen of animals is more or less distended and acts as a blood store. In stress or disease states (e.g., severe bleeding), the spleen contracts and can release stored blood into the circulation. II. STRUCTURE The spleen is a parenchymatous organ made up of a stroma (capsule, trabeculae and reticular fibres and cells) and a parenchyma generically called "pulp", due to the pulpy appearance that macroscopically presents a spleen when cut. 1. Stroma The spleen is surrounded by a capsule of dense connective tissue, in which a variable number of smooth muscle fibres and elastic networks can be seen. This capsule is lined by a mesothelium that is part of the general peritoneum and thickened in the hilum, where it joins the peritoneal ligaments and through which arteries and nerves enter as well as veins and lymphatic vessels. The trabeculae start from the capsule, made up of fibroblasts, collagen fibres, elastic fibres and smooth muscle fibres and through which arteries, veins, lymphatics and nerves pass. 1 Figure 1: Pig spleen (perfused). The capsule and trabeculae (arrows) and a lymphoid follicle (*) can be seen. Light microscopy (LM). The collagen fibres of the trabeculae are continued with a three-dimensional network of reticular fibres, which are argyrophilic (which are stained with silver techniques), type III collagen fibres. In close association with these fibres there are reticular cells of stellate morphology that synthesize and completely envelop the reticular fibres. These reticular cells and fibres form the framework of the spleen. 2. Parenchyma In the spleen parenchyma we can distinguish three zones or compartments, morphologically and functionally, very different, and they are: White splenic pulp: made up of the periarterial lymphoid sheaths and the lymphoid follicles or corpuscles of Malpighi (not to be confused with the renal corpuscle that also receives that name). Red splenic pulp: made up of sheathed capillaries, venous sinuses and splenic or Billroth cords. Marginal zone: a transition zone between the white splenic pulp and the red splenic pulp. As in the spleen nutritional and functional circulation coincide, to describe its parenchyma we are going to follow the route of the blood supply. The branches of the splenic artery penetrate through the hilum, run along the capsule and enter the trabeculae where they branch repeatedly, giving rise to the trabecular arteries, which are muscular arteries. These arteries leave the trabeculae and enter the splenic parenchyma. Then, the tunica externa of the artery is replaced by an envelope of lymphoid cells and the artery is renamed the central artery, forming a periarterial lymphoid sheath. This periarterial lymphoid sheath is made up mainly of T cells, although there are also antigen-presenting cells (interdigitating cells) and macrophages. 2 Figure 2: White splenic pulp. Periarterial lymphoid sheath. LM. In some areas, these lymphoid formations proliferate giving place to lymphoid nodules or lymphoid follicles, which may present a germinal centre. These lymphoid follicles or Malpighi's corpuscles move the central artery to the periphery losing its central position, being called eccentric or follicular artery. Lymphoid follicles are mainly made up of B cells, as well as follicular dendritic cells (which retain antigen/antibody complexes for a long time) and macrophages. 3 4 Figure 3: White splenic pulp. Three lymphoid follicles are seen. Light Microscopy (LM). Figure 4: Detail of the eccentric artery of a lymphoid follicle. LM. The central and follicular arteries are muscular arteries that emit numerous collateral capillaries, which supply the lymphoid structures, along their path through the white splenic pulp. These arteries are decreasing in size; at one point, they abruptly branch and give rise to five or six vessels called penicillar arterioles, which are so named because they resemble the bristles of a brush, and which still have one or two layers of lymphocytes surrounding them, so they still belong to the white splenic pulp. Each penicillar arteriole branches into two or three capillaries, one of which may show a thickening in its walls called the Schweigger-Seidel sheath or periarterial macrophage sheath. For this reason, these capillaries, which are discontinuous, are called sheathed capillaries. The periarterial macrophage sheath is made up of numerous macrophages housed in the stromal network of reticular fibres and cells. 5 Figure 5: Red splenic pulp. Numerous sheathed capillaries surrounded by splenic cords. Light Microscopy. All capillaries, both simple and sheathed, flow into the venous sinuses, which are tortuous and dilated ducts. They are made up of rounded endothelial cells, a discontinuous basement membrane, and a layer of reticular cells with reticular fibres that provide support. Endothelial cells have a large number of microfilaments in their cytoplasm that facilitate their contraction. The venous sinuses flow into the pulp veins, which drain into the trabecular veins that converge to form the hilum veins to finally give rise to the splenic vein. Surrounding the venous sinuses are the splenic cords that are constituted, mainly by macrophages that are housed in the stromal framework of reticular fibres and reticular cells. In the splenic cords the haemocatheretic function (blood filter) is carried out by macrophages and due to the lack of flexibility of old erythrocytes. The marginal zone is a transition zone between the white and red splenic pulp and is of great importance in the immune response. It is formed by a concentric framework of reticular fibres and reticular cells (it acquires the rounded shape of the follicles and lymphoid sheaths) and is occupied by specialized B cells and macrophages. In the closest part to the red splenic pulp the marginal sinus receives the collateral capillaries that supply the lymphoid structures. 6 Figure 6: Splenic cords and venous sinus lumen. Scanning electron microscopy (SEM). Figure 7: Detail of a macrophage of the splenic cords with numerous filopodia. SEM. 7 III. THEORIES ON SPLENIC CIRCULATION The anastomosis of capillaries with the venous system is controversial, and there are currently three theories regarding the type of union. The first theory, or theory of closed circulation, defends that all capillaries flow directly into the venous sinuses. The open circulation theory suggests that all capillaries open in the splenic cords and blood then enters the venous sinuses through discontinuities in their walls. The semi-open circulation theory proposes the existence of both circulations depending on the physiological state of the individual. When the spleen is distended (good physiological state) the last endothelial cell of the capillaries and the first endothelial cell of the venous sinuses separate and the blood passes to the splenic cords and after being filtered enters the venous sinuses. In a contracted spleen (stress, bleeding, various pathologies) the endothelial cells of the capillaries and venous sinuses anastomose and form an uninterrupted tubular structure.