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The differentiation of T cells occurs in the cortex of the thymus. In humans the thymus appears early in fetal development and continues to grow until puberty , after which it begins to shrink. The decline of the thymus is thought to be the reason T-cell production decreases with age. The thymocytes then move to the medulla of the thymus, where further differentiation occurs. Positive and negative selection destroy a great number of thymocytes; only about 5 to 10 percent survive to exit the thymus.
Those that survive leave the thymus through specialized passages called efferent outgoing lymphatics, which drain to the blood and secondary lymphoid organs. The thymus has no afferent incoming lymphatics, which supports the idea that the thymus is a T-cell factory rather than a rest stop for circulating lymphocytes.
In birds B cells mature in the bursa of Fabricius. The process of B-cell maturation was elucidated in birds—hence B for bursa. In mammals the primary organ for B-lymphocyte development is the bone marrow, although the prenatal site of B-cell differentiation is the fetal liver. Unlike the thymus, the bone marrow does not atrophy at puberty, and therefore there is no concomitant decrease in the production of B lymphocytes with age.
The secondary lymphoid organs serve two basic functions: The lymph nodes, or lymph glands, are small, encapsulated bean-shaped structures composed of lymphatic tissue. Thousands of lymph nodes are found throughout the body along the lymphatic routes, and they are especially prevalent in areas around the armpits axillary nodes , groin inguinal nodes , neck cervical nodes , and knees popliteal nodes. The nodes contain lymphocytes, which enter from the bloodstream via specialized vessels called the high endothelial venules.
T cells congregate in the inner cortex paracortex , and B cells are organized in germinal centres in the outer cortex. Lymph, along with antigens, drains into the node through afferent incoming lymphatic vessels and percolates through the lymph node , where it comes in contact with and activates lymphocytes. Activated lymphocytes, carried in the lymph, exit the node through the efferent outgoing vessels and eventually enter the bloodstream, which distributes them throughout the body.
The spleen is found in the abdominal cavity behind the stomach. Although structurally similar to a lymph node, the spleen filters blood rather than lymph. One of its main functions is to bring blood into contact with lymphocytes. The functional tissue of the spleen is made up of two types of cells: The splenic artery enters the red pulp through a web of small blood vessels, and blood-borne microorganisms are trapped in this loose collection of cells until they are gradually washed out through the splenic vein.
The white pulp contains both B and T lymphocytes. T cells congregate around the tiny arterioles that enter the spleen, while B cells are located in regions called germinal centres, where the lymphocytes are exposed to antigens and induced to differentiate into antibody -secreting plasma cells.
Another group of important secondary lymphoid structures is the mucosa-associated lymphoid tissues. These tissues are associated with mucosal surfaces of almost any organ, but especially those of the digestive, genitourinary, and respiratory tracts, which are constantly exposed to a wide variety of potentially harmful microorganisms and therefore require their own system of antigen capture and presentation to lymphocytes.
Other, less-organized regions of the gut also play a role as secondary lymphoid tissue. The host of secondary lymphoid organs provides a system of redundancy for antigen sampling by the cells of the immune system. Removal of the spleen, selected lymph nodes, tonsils, or appendix does not generally result in an excessive increase in disease caused by pathogenic microorganisms.
However, the importance of the primary lymphoid organs is clear. For example, two autoimmune diseases, DiGeorge syndrome and Nezelof disease, result in the failure of the thymus to develop and in the subsequent reduction in T-cell numbers, and removal of the bursa from chickens results in a decrease in B-cell counts.
The destruction of bone marrow also has devastating effects on the immune system , not only because of its role as the site of B-cell development but also because it is the source of the stem cells that are the precursors for lymphocyte differentiation.
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