The central and peripheral lymphoid organs are responsible for the production, maturation, and storage of large numbers of immune system cells including the B and T lymphocytes. These organs and tissues are widely distributed throughout the body and provide different, but often overlapping, functions (Fig. 13.12). The central lymphoid organs are comprised of the bone marrow and the thymus and are responsible for immune cell production and maturation. The tissues and cells of the peripheral lymphoid system store the cells of the immune system where they function to concentrate and process antigen as well as support cellular processes necessary for development of fully functioning, adaptive immune responses. The peripheral lymphoid tissues are comprised of the lymph nodes, spleen, tonsils, appendix, Peyer patches in the intestine, and mucosa-associated lymphoid tissues in the respiratory, gastrointestinal, and reproductive systems. Networks of lymph channels, blood vessels, and capillaries connect the lymphoid organs and transport immune cells, antigens, and cellular debris throughout the body.
The thymus is an elongated, bilobed structure located in the mediastinum above the heart and serves as a specialized immune system organ. Each lobe is surrounded by a connective tissue capsule layer and is divided into lobules. The lobules can be divided into an outer cortex and a central medulla, which play different roles in the process of T-lymphocyte maturation. The outer cortex contains densely packed immature T lymphocytes (thymocytes). The inner medulla is a less dense area of tissue that contains fewer but more histologically mature lymphocytes. The medulla is comprised of Hassall corpuscles but also stores DCs and macrophages (Fig. 13.13).
The thymus is essential to the development of the immune system because it is responsible for the production of mature, immunocompetent T lymphocytes. The thymus is a fully developed organ at birth, weighing approximately 15 to 20 g. It is most active in the neonatal and preadolescent periods. At puberty, when the immune cells are well established in peripheral lymphoid tissues, the thymus begins to atrophy and is replaced by adipose tissue. Nevertheless, residual T-lymphocyte production continues throughout adult life. Precursor T (pre-T) cells enter the thymus as functionally and phenotypically immature T cells. They then mature during different cycles and then move from the cortex to the medulla until they are released into the peripheral lymphoid tissues. Rapid cell division, maturation, and selection occur in the cortex under the influence of thymic hormones and cytokines. As the T cells mature, they develop the TCRs that differentiate them from other types of T cells. The majority of the thymocytes die in the cortex during the process of gene rearrangement and maturation because they fail to develop the appropriate receptor types on their cell membranes. Only those T cells capable of recognizing foreign antigen displayed by self-MHC are allowed to mature. This process is called thymic selection. Mature, immunocompetent T-helper and T-cytotoxic cells leave the thymus in 2 to 3 days and enter the peripheral lymphoid tissues through the bloodstream.
Lymph nodes are small aggregates of lymphoid tissue located along lymphatic vessels throughout the body. The lymphatic vessels carry lymph, which is a clear sometimes yellow-tinged fluid that contains a variety of white blood cells (pre-dominantly lymphocytes) and transports cellular debris and organisms to the lymph modes to be removed from the body. Each lymph node processes lymph from a discrete, adjacent anatomic site. Lymph nodes are congregated in the axillae and groin and along the great vessels of the neck, thorax, and abdomen. The lymph nodes receive lymph from the collecting ducts, which ultimately drain into the thoracic duct located in the left side of the chest at the level of the subclavian vein. Lymph nodes have two functions: removal of foreign material from lymph before it enters the bloodstream and serving as centers for proliferation and response of immune cells.
Lymph nodes are bean-shaped, encapsulated tissues, approximately 0.5 to 1 cm in diameter. Lymph enters the node through afferent lymph channels and leaves through the efferent lymph vessels located in the deep indentation of the hilus. Lymphocytes and macrophages move slowly through the lymph nodes so that they have adequate time to engulf microorganisms and interact with circulating antigen. The lymphatic system provides a large surface upon which macrophages and DCs can more easily present antigens to T lymphocytes.
Lymph nodes are divided into three distinct and specialized areas—an outer cortex, a paracortex, and an inner medulla (Fig. 13.14). The T lymphocytes predominate in the paracortex and the B lymphocytes predominate in the follicles and germinal centers of the outer cortex. The T lymphocytes proliferate when antigens enter the paracortex of the lymph node. They then migrate to the outer cortex so that they can interact with B lymphocytes that are stored there. Within the follicles the lymphocytes continue to mature, replicate, and interact with the PACs present in the nodes (macrophages and follicular DCs). Activated B cells then migrate to the medulla of the lymph node, where they complete their maturation into plasma cells. Large quantities of antibodies are then released into the systemic circulation.
The spleen is a large, ovoid secondary lymphoid organ located high in the left upper quadrant of the abdominal cavity between the diaphragm and the stomach. The spleen filters antigens from the blood and is important in the response to systemic infections. It is divided into two systems: the white pulp and the red pulp. The red pulp is well supplied with arteries and venous sinusoids and is the area where senescent and injured red blood cells are removed. The white pulp contains lymphatic nodules and diffuse lymphoid tissue where concentrated areas of B and T lymphocytes permeated by macrophages and DCs exist. The lymphocytes (primarily T cells) that surround the central arterioles form the area called the periarterial lymphoid sheath. There is also a diffuse marginal zone that contains the follicles and germinal centers and is rich in B cells. This separates the white pulp from the red pulp and allows lymphocytes to move easily between the blood and the lymphatic tissue. A sequence of activation events similar to that seen in the lymph nodes occurs in the spleen.
Other Secondary Lymphoid Tissues
Other secondary lymphoid tissues include the mucosa- associated lymphoid tissues, which are nonencapsulated clusters of lymphoid tissues located around membranes lining the respiratory, digestive, and urogenital tracts. These organ systems constantly came in contact with pathogens and toxins and, therefore, require the presence of immune cells in order to respond to the potential invasion by pathogens and harmful substances. In some tissues, the lymphocytes are organized in loose, nondescript clusters, but in other tissues such as the tonsils, Peyer patches in the intestine, and the appendix, their structure is better organized. These tissues contain all the cellular components (i.e., T cells, B cells, macrophages, and DCs) required to mount an immune response. Immunity at the mucosal layers helps to exclude many pathogens from the body and, as a result, protects the more vital internal structures.