Immunology. Richard Coico
the major lymphoid organs will be described which include the bone marrow, thymus, lymph nodes, and spleen. Given the coordination required for optimal immune responses to fully manifest, the anatomy of the immune system, including the strategic location of its major organs, is designed to maximize the ability of immune cells to efficiently detect and respond to antigens and to then disperse effector mechanisms throughout the body. A major route of immune cell and antigen transport is the lymphatic system.
THE LYMPHATIC SYSTEM
The lymphatic system is part of the vascular system comprising a network of lymphatic vessels that contain a clear fluid called lymph. Lymph is a fluid similar to plasma and contains lymphocytes, waste products and cellular debris, and, importantly, bacteria and proteins that stimulate immune responses. All interstitial spaces are drained by the lymphatic system, ensuring that wherever a foreign, potentially infectious pathogen enters the body, it will be swept away and deposited within a draining lymph node where antigen‐presenting cells and antigen‐specific T and B cells can initiate an immune response (Figure 2.1).
Primary and Secondary Lymphoid Organs
The organs in which lymphocyte maturation, differentiation, and proliferation take place are divided into two categories: primary and secondary organs. The primary or central lymphoid organs are those in which the maturation of B and T lymphocytes into antigen‐recognizing lymphocytes occurs. In other words, these are the organs where gene rearrangements occur to generate functional antigen‐specific BCRs and TCRs expressed by B and T cells, respectively. Mature B cells differentiate to fully mature cells within the bone marrow. Historically, the term “B cell” is derived from developmental studies in birds that demonstrated that antibody‐forming lymphocytes differentiate within an organ unique to birds called the bursa of Fabricius (hence, “B” for bursa). In contrast, T cells differentiate only partially within the bone marrow. Precursor cells destined to become mature T cells undergo final maturation within the thymus gland (hence, “T” for thymus). Histological characteristics of the thymus are discussed in the next section.
Mature B and T cells migrate through the bloodstream and lymphatic system to the peripheral lymphoid tissues, including the lymph nodes and spleen. Collectively, these are referred to as the secondary lymphoid organs and this is where antigen‐driven activation (proliferation and differentiation) of B and T cells takes place (Figure 2.2). Histological properties of the secondary lymphoid organs are also presented below.
Figure 2.1. Lymphoid fluid draining interstitial spaces.
Source: © John Wiley & Sons, Inc.
Figure 2.2. Distribution of lymphoid tissues in the body.
Thymus Gland.
The thymus gland is a bilobed structure, derived from the endoderm of the third and fourth pharyngeal pouches. During fetal development, the size of the thymus increases. The growth continues until puberty. Thereafter, the thymus undergoes atrophy with aging.
The thymus is a lymphoepithelial organ and consists of epithelial cells organized into cortical (outer) and medullary (central) areas that are infiltrated with lymphoid cells (thymocytes) (Figure 2.3A). The cortex is densely populated with lymphocytes of various sizes, most of which are immature, and scattered macrophages involved in clearing apoptotic thymocytes. Figure 2.3B shows a section through normal human thymus tissue.
Secondary Lymphoid Organs.
The secondary lymphoid organs have two major functions: (1) they are highly efficient in trapping and concentrating foreign substances, and (2) they are the main sites of production of antibodies and the induction of antigen‐specific T lymphocytes. In other words, they are where immune responses are initiated.
Figure 2.3. (A) Cellular organization of the thymus.
Source: Rosen FS and Geha RS (2007). Reproduced with permission of Taylor & Francis.
(B) Section of an adolescent thymus showing capsule, septa, cortex, medulla, and Hassall’s corpuscle.
Source: Photograph by Dr John Lewis, SUNY Downstate College of Medicine, New York.
The major secondary lymphoid organs are the spleen and the lymph nodes. In addition, tonsils, appendix, clusters of lymphocytes distributed in the lining of the small intestine (Peyer’s patches), and lymphoid aggregates spread throughout mucosal tissue are considered secondary lymphoid organs. These secondary lymphoid organs are found in various areas of the body, such as the linings of the digestive tract, in the respiratory and genitourinary tracts, in the conjunctiva, and in the salivary glands, where mature lymphocytes interact with antigen and undergo activation. These mucosal secondary lymphoid organs have been given the name mucosa‐associated lymphoid tissue (MALT). Those lymphoid tissues associated with the gut are gut‐associated lymphoid tissue (GALT); those associated with the bronchial tree are termed bronchus‐associated lymphoid tissue (BALT).
The Spleen
The spleen is the largest of the secondary lymphoid organs (Figure 2.4A). It is highly efficient in trapping and concentrating foreign substances carried in the blood. It is the major organ in the body in which antibodies are synthesized and from which they are released into the circulation. The spleen is composed of white pulp, rich in lymphoid cells, and red pulp, which contains many sinuses as well as large quantities of erythrocytes and macrophages, some lymphocytes, and a few other cell types. Figure 2.4B shows a section of human spleen illustrating the red and white pulp areas.
The areas of white pulp are located mainly around small arterioles, the peripheral regions of which are rich in T cells; B cells are present mainly in germinal centers. Approximately 50% of spleen cells are B lymphocytes; 30–40% are T lymphocytes. After antigenic stimulation, the germinal centers contain large numbers of B cells and plasma cells. These cells synthesize and release antibodies.
Lymph Nodes
Lymph nodes are small ovoid structures (normally less than 1 cm in diameter) found in various regions throughout the body (see Figure