Lymphoid Organs I PDF

_____________ LESSON 16 _____________ LYMPHOID ORGANS (I) The lymphoid system is made up of a set of organs that have in common a stroma made up of reticular or reticulo-epithelial tissue and a parenchyma made up of lymphocytes. Its function is to protect the animal body against biological agents a...

_____________ LESSON 16 _____________ LYMPHOID ORGANS (I) The lymphoid system is made up of a set of organs that have in common a stroma made up of reticular or reticulo-epithelial tissue and a parenchyma made up of lymphocytes. Its function is to protect the animal body against biological agents and molecules, which it recognizes as foreign ones, either with an endogenous or exogenous origin, giving rise to a defensive response, called the immune response. From a functional point of view, the organs and tissues of the lymphoid system are considered primary and secondary. In the primary lymphoid organs, the genesis and differentiation of the lymphoid cells takes place, becoming immunocompetent and, in the secondary organs, the already immunocompetent lymphocytes participate in the immune response. In mammals the primary lymphoid organs are the bone marrow and thymus as well as Peyer's patches in ruminants and in the case of birds, bursa of Fabricius. The secondary lymphoid organs can be groups of lymphocytes or be constituted as true conventional organs. The former lack a capsule and are called mucosa-associated lymphoid tissue (MALT), among which Peyer's patches and tonsils can be distinguished by their importance. The latter appear encapsulated and forming a true organ: the lymph nodes, the haemolymph nodes and the spleen. II. PRIMARY LYMPHOID ORGANS 1. Thymus The thymus is a primary lymphoid organ of a lymphoepithelial nature. In the thymus the T lymphocyte colony-forming units (TL-CFUs) differentiate into T lymphocytes and undergo proliferation independent of possible antigenic stimulation. After their differentiation (immunocompetence) they leave the thymus and colonize the T areas of the secondary lymphoid organs. The thymus develops earlier than the other lymphoid organs, in such a way that in the prenatal period it has been completely formed, a fact that does not occur with the spleen or with the lymph nodes. The thymus is a lobed parenchymal organ. Each of the lobes is surrounded by a thin capsule of connective tissue, which projects inwards through thin septa that subdivide the lobes into a variable number of lobule of a polyhedral or rectangular shape. Two regions can be distinguished in the lobules, a peripheral basophilic region called the cortex and another central region of much paler staining, eosinophilic, the medulla. The lobules are not totally separated from each other, since the medullary areas of adjacent lobules are confluent, therefore they are also called pseudolobules. Several cell types can be distinguished in the thymus: T cells (immature and mature), reticulo-epithelial cells (which make up the stroma of the organ), a moderate number of macrophages and interdigitating cells (antigen-presenting cells located only in the medulla). If the thymus has initiated involution, adipocytes can be seen. Figure 1: Thymic lobes showing the cortex and medulla. Figure 2: Detail of the previous one. A Hassall’s corpuscle is seen in the medulla of the lobe. The reticulo-epithelial cells constitute the stroma of the thymus and consist of cells with stellate morphology, with an evident euchromatic nucleus and nucleolus and numerous intermediate keratin filaments in their cytoplasm. They are linked together by desmosomes. These cells, in addition to their mechanical support function, produce polypeptides, which provide the appropriate microenvironment for the differentiation and proliferation of T cells. There are six types of reticulo-epithelial cells depending on their location and degree of maturation. Type VI reticulo-epithelial cells, located in the thymic medulla, are the ones that make up characteristic structures of the thymus, Hassall's corpuscles, which are constituted by the association of several degenerating reticulo-epithelial cells. The cortex of the lobules is made up of T cells and macrophages. In the outer cortex, large lymphocytes (immature T cells) predominate, proliferating in the subcapsular region to give rise to cells that will enter the differentiation pathway, acquiring membrane receptors and being instructed. Thus, lymphocytes that do not recognize the individual's proteins or the MHC (major histocompatibility complex) as their own die by apoptosis, being phagocytosed by macrophages. The medulla is made up of differentiated T cells (immunocompetent) that can participate in the immune response, macrophages and interdigitating cells (stellate and with numerous lysosomes). The continuous capillaries of the cortex constitute the so-called blood-thymus barrier. This barrier prevents differentiating lymphocytes from coming into contact with antigens and is composed of the continuous capillary endothelium, a basement membrane, the pericyte, and reticulo-epithelial cell extensions. Thymic involution The involution process is a physiological fact and is related to age. As a result of involution in adult animals, the thymus transforms into a mass of adipose tissue that contains islets of parenchyma, where reticulo-epithelial cells predominate and lymphocytes are scarce. 2. Bursa of Fabricius The Bursa of Fabricius is a lymphoepithelial organ of birds, which participates in the genesis and differentiation of B cells. The functional equivalent of this organ in mammals is the bone marrow, but is does not mean that birds do not have also bone marrow. It is shaped like a rounded sac and is located dorsal to the wall of the cloaca with which it is communicated by a small opening. The wall of the cloaca or of Bursa of Fabricius is composed of three tunics, which from the lumen of the organ towards the periphery are: mucosa/submucosa, muscular and a very thin serosa. The mucosa projects towards the lumen of the organ forming approximately twelve folds. The epithelium of the folds is columnar pseudostratified, except at the apex of each follicle, where a single layer of columnar epithelial cells is observed. The lymphoid follicles have a polyhedral morphology and are very close to each other, separated by a small band of connective tissue, which comes from the submucosa. The follicles have two areas: the cortex and the medulla. The lymphocytes are located within a network of epithelial reticular cells. Like the thymus, it undergoes involution, a process that begins approximately two months after birth. Figure 3: Folds of Bursa of Fabricius. Figure 4: Detail of the fold of the previous figure. The pseudostratified epithelium and a lymphoid follicle are observed. III. SECONDARY LYMPHOID ORGANS The secondary lymphoid organs contain lymphoid follicles, differentiating two types according to their morphology and function: primary and secondary lymphoid follicles. Primary lymphoid follicles are spherical or ovoid structures, formed by a network of reticular fibers (type III collagen) and reticular cells (stellate cells that synthesize and surround reticular fibers). These cells bind to follicular dendritic cells, forming a framework in which numerous B cells, unstimulated and memory, and some T cells lodge. The reticular cells have a fibroblastic origin while the follicular dendritic cells come from blood precursors of the bone marrow. Follicular dendritic cells have an euchromatic nucleus, few organoids and very evident cytoplasmic processes, which give them a stellate shape. Its function is the presentation of antigens to B cells. Secondary lymphoid follicles arise from the primary ones in response to antigen recognition. These follicles are areas of active proliferation of B cells. They are made up of ovoid structures with a germinal center surrounded by a mantle or crown. The germinal center is composed of lymphoblasts (or centroblasts, so called because they are in the germinal center of the lymphoid follicle), large, medium and small B cells, some T cells and macrophages, which are arranged on the stroma, previously described, of reticular cells, follicular dendritic cells and reticular fibers. The mantle of the secondary lymphoid follicle is made up of small, densely packed lymphocytes that are primarily memory B cells, along with some T cells. Figure 5: Secondary lymphoid follicles showing the germinal centre (*). 1. Mucosa-associated lymphoid tissue (MALT) The mucosa-associated lymphoid tissue (MALT) constitutes an independent immune system, responsible for protecting the mucosa from pathogens, thus preventing the systemic immune response. This lymphoid tissue is structured in diffuse infiltrations and large accumulations. Diffuse lymphocyte infiltrations occur in the digestive epithelium and in the lamina propria of the digestive, respiratory and genitourinary mucosa. Large accumulations of lymphoid tissue associated with mucosa occur in the lamina propria and submucosa of the digestive system, where isolated or groups of lymphoid follicles such as Peyer's patches can be differentiated as well as in the lamina propria of the respiratory system, especially in the bronchi, in the form of isolated lymphoid follicles, where they make up the bronchiassociated lymphoid tissue (BALT). In addition, accumulations of lymphoid tissue appear in the mucosa of the transit zone between the digestive and respiratory systems, constituting the tonsils. a) Peyer's patches They are lymphoid formations made up of follicular aggregates located in the lamina propria and submucosa of the small intestine and ileocecal valve. According to their location, they have been classified into jejunal and ileal or ileocecal Peyer's patches. In general, they are considered a secondary lymphoid organ, although in ruminants ileal Peyer's patches are a primary lymphoid organ with an important role in the development of B cells. Peyer's patches, whatever the type, are made up of 3 clearly differentiated regions: dome (area between the lymphoid follicle and the epithelium), lymphoid follicle and interfollicular area (space between the follicles formed by diffuse lymphoid tissue with a high number of T cells). b) Tonsils The tonsils are partially encapsulated accumulations of lymphoid tissue that are arranged in the transit between the respiratory and digestive systems. The tonsils located on the tongue and oropharynx are lined by a squamous stratified epithelium and those located in the nasopharynx by a columnar pseudostratified epithelium. The surface of the tonsils may be smooth or have deep invaginations, called tonsillar crypts. The lymphoid areas of the tonsils lie below the epithelium. Between the lymphoid follicles appear interfollicular areas of diffuse lymphoid tissue composed mainly of T cells. The follicles can be primary and secondary. Figure 6: Peyer's patches: lymphoid follicles in the lamina propria-submucosa of the ileum. Figure 7: Image of the tonsil showing the epithelium, crypts and lymphoid follicles