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Normal and Non-Specifically Reactive Lymph Nodes

Normal nodeLYMPH nodes are a combination of burglar alarm and West Point. Like a burglar alarm they are on guard against intrusive antigens. Like West Point, the nodes are in the business of training a militant elite:   lymphoid cells that respond to the intruder by making antibodies and forming a corps of B and T-cells that will remember the intruder's imprint for years. Lymph node components (image) that we'll examine include:

• capsule
• follicles
• germinal centers
• parafollicular cortex
• medullary cords
• sinuses
• high endothelial venules
• afferent / efferent lymphatics

Follicular hyperplasia with multiple secondary follicles
        The lymph node is composed of an outer shell called the cortex and an inner kernel called the medulla. The cortex, in turn, is made up of spherical clusters of B-lymphocytes called follicles. If the "virgin" B-cells are unexposed to antigen, they compose homogeneous primary follicles. If the B-cells have been stimulated by antigen and are in the process of proliferating and transforming themselves, they form a pale-staining germinal center surrounded by a mantle zone of smaller, darker B-lymphocytes. The whole assembly is called a secondary follicle (image) and is populated by 4-5 clones of B-cells that have emerged from the primary follicle.
         Among the follicles is the parafollicular cortex, called paracortex for short, where the T-lymphocytes live. Also present are the high endothelial venules, which are vessels from which vagabond lymphocytes re-enter the lymph node from the blood.
        The deep part of the node called the medulla has two elements: 1) the coalescing lymphoid sinuses containing macrophages and scattered lymphocytes and 2) the lymphoid tissue between the sinuses, called the medullary cords (image), which are often the haunt of plasma cells.
        Let's see what happens to antigens as they enter a node and trigger an immune response. The lymph-borne antigen flows along an afferent lymphatic channel from its origin in skin lesions, upstream cancers, or disruptions. The afferent lymphatic pierces the node's thin fibrous capsule to dump the lymph and its contents into the subcapsular sinus. From there the antigen flows down the trabecular sinuses, which are lymph channels within the node that accompany the fibrous septa called trabeculae. The lymph and the antigens flow toward the hilum, where the lymph node is attached to efferent blood and lymphatic vessels that carry away their respective fluids.
         As the antigens traverse the sinuses, they are captured and processed by the lining macrophages. Eventually the antigens become available for presentation to the lymphoid cells. The presenting cells are probably the sinusoidal macrophages and, more importantly, dendritic cells that reside either in the paracortex (interdigitating dendritic cells) or the follicles (follicular dendritic cells). Paracortical T-cells, mostly CD4(+) T-helper cells, are key players in the recognition of antigen. They are so provoked by its presence that, unable to contain themselves, they transmit their excitement to their B-cell counterparts in the as-yet unstimulated primary follicle.
Germinal center Germinal center cells
         Nudged by the T-cells, the primary follicle B-cells with surface immunoglobulin most closely matching the irritating antigen begin to proliferate and transform. The variable regions of their immunoglobulin receptors undergo somatic hypermutation, resulting in some cases in a better fit with the antigen, in other cases in a worse fit. The former are encouraged to continue to proliferate while the latter receive apoptotic signals and die.
        From a morphologic point of view, the small, virgin, resting B-cells become the larger, more irregular small-cleaved and large cells of the active germinal center (images). Because these activated B-cells have larger and more empty-appearing nuclei, the germinal centers show up as pale disks in the cortex on H&E stained slides.
        The germinal centers also demonstrate abundant mitotic figures and so-called "tingible-body macrophages". These macrophages have imbibed bits of nuclear debris from dead B-cells that went belly-up in this survival-of-the-fittest milieu, because their immunoglobulin failed to match the antigen adequately. Some of the features that help to distinguish a reactive germinal center from a neoplastic lymphoma follicle are:
• a very brisk mitotic rate
• tingible-body macrophages
• a well-developed mantle zone
• polarization, with darker staining cells dominating the deeper half of the germinal center
         The B-cells that survive the tumultuous, Darwinian struggle within the germinal center eventually differentiate into either plasma cells or memory B-cells. Minute crafters of antibodies, the plasma cells migrate to the medullary cords or leave the lymph node altogether to resettle in the body's distant shores. All this is a dynamic process. Germinal centers appear about a week after the node is challenged by an immunogenic antigen and gradually subside unless further challenged.
         Other types of reactive lymph node hyperplasia also occur, including hyperplasia of the paracortical region or of the sinus cells, the latter called "sinus histiocytosis". The different kinds of hyperplasias may occur by themselves or in combination.

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