Lymph nodes filter antigen from the lymph fluid.

Directly interior to a lymph node's fibrous capsule is the subcapsular sinus. This allows lymph, an ultrafiltrate of blood, to traverse from the afferent lymph vessels, through the sinuses, and out the efferent vessels.

The sinuses are studded with macrophages, which remove 99% of all delivered antigens.

Interior to the subcapsular sinus is the cortex, which contains primary follicles, secondary follicles, and the interfollicular zone. Follicles within the cortex are major sites of B-cell proliferation, whereas the interfollicular zone is the site of antigen-dependent T-cell differentiation and proliferation. The deepest structure within the lymph node is the medulla, consisting of cords of plasma cells and small B lymphocytes that facilitate immunoglobulin secretion into the exiting lymph.

The lymph node, with its high concentration of lymphocytes and antigen-presenting cells, is an ideal organ for receiving antigens that gain access through the skin or gastrointestinal tract. Nodes have considerable capacity for growth and change. Lymph node size depends on the person's age, the location of the lymph node in the body, and antecedent immunological events. In neonates, lymph nodes are barely perceptible, but a progressive increase in total lymph node mass is observed until later childhood. Lymph node atrophy begins during adolescence and continues through later life.

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The specific functions are determined by anatomic position within the node (cortex, medulla, and paracortex areas).

Exposure to antigen through a break in the skin or mucosa results in antigen being taken up by an antigen-presenting cell and carried via lymphatic channels to the nearest lymph node. Lymph channels course throughout the body except for the brain and the bones. Lymph enters the node through the afferent vessel and leaves through an efferent vessel. Because antigen-presenting cells pass through lymph nodes, they present antigen to lymphocytes residing there. Lymphocytes in a node are constantly being replaced by antigen-naïve lymphocytes from the blood. They are retained in the node via special homing receptors. B cells populate the lymphoid follicles in the cortex; T cells populate the paracortical regions. When a B cell encounters an antigen to which its surface immunoglobulin can bind, it stays in the follicle for a few days and forms a germinal center where the immunoglobulin gene is mutated in an effort to make an antibody with higher affinity for the antigen. The B cell then migrates to the medullary region, differentiates into a plasma cell, and secretes immunoglobulin into the efferent lymph.

When a T cell in the node encounters an antigen it recognizes, it proliferates and joins the efferent lymph. The efferent lymph laden with antibodies and T cells specific for the inciting antigen passes through several nodes on its way to the thoracic duct, which drains lymph from most of the body. From the thoracic duct, lymph enters the bloodstream at the left subclavian vein. Lymph from the head and neck and the right arm drains into the right subclavian vein. From the bloodstream, the antibody and T cells localize to the site of infection.

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