LYMPH NODES

Lymph nodes are the sites where immune responses are mounted to antigens in lymph. They are encapsulated beanshaped structures containing a reticular network packed with lymphocytes, macrophages, and dendritic cells. Clustered at junctions of the lymphatic vessels, lymph nodes are the first organized lymphoid structure to encounter antigens that enter the tissue spaces. As lymph percolates through a node, any particulate antigen that is brought in with the lymph will be trapped by the cellular network of phagocytic cells and dendritic cells (follicular and interdigitating). The overall architecture of a lymph node supports an ideal microenvironment for lymphocytes to effectively encounter and respond to trapped antigens. Morphologically, a lymph node can be divided into three roughly concentric regions: the cortex, the paracortex, and the medulla, each of which supports a distinct microenvironment.

Fig

 The outermost layer, the cortex, contains lymphocytes (mostly B cells), macro-phages, and follicular dendritic cells arranged in primary follicles. After antigenic

challenge, the primary follicles enlarge into secondary follicles, each containing a germinal center. In children with B-cell deficiencies, the cortex lacks primary follicles and germinal centers. Beneath the cortex is the paracortex, which is populated largely by T lymphocytes and also contains interdigitating dendritic cells thought to have migrated from tissues to the node. These interdigitating dendritic cells express high levels of class II MHC molecules,which are necessary for presenting antigen to TH cells. Lymph nodes taken from neonatally thymectomized mice have unusually few cells in the paracortical region; the paracortex is therefore sometimes referred to as a thymus-dependent area in contrast to the cortex, which is a thymus-independent area. The innermost layer of a lymph node, the medulla, is more sparsely populated with lymphoid-lineage cells; of those present, many are plasma cells actively secreting antibody molecules.

As antigen is carried into a regional node by the lymph, it is trapped, processed, and presented together with class II MHC molecules by interdigitating dendritic cells in the paracortex, resulting in the activation of TH cells. The initial activation

of B cells is also thought to take place within the T-cell-rich paracortex. Once activated, TH and B cells form small foci consisting largely of proliferating B cells at the edges of the paracortex. Some B cells within the foci differentiate

into plasma cells secreting IgM and IgG. These foci reach maximum size within 4–6 days of antigen challenge. Within 4–7 days of antigen challenge, a few B cells and TH cells migrate to the primary follicles of the cortex. It is not known what causes this migration.Within a primary follicle, cellular interactions between follicular dendritic cells, B cells, and TH cells take place, leading to development of a secondary follicle with a central germinal center. Some of the plasma cells generated in the germinal center move to the medullary areas of the lymph node, and many migrate to bone marrow.Afferent lymphatic vessels pierce the capsule of a lymph node at numerous sites and empty lymph into the subcapsular sinus (see Fig B). Lymph coming from the tissues percolates slowly inward through the cortex, paracortex, and medulla, allowing phagocytic cells and dendritic cells to trap any bacteria or particulate material (e.g., antigen-antibody complexes) carried by the lymph. After infection or the introduction of other antigens into the body, the lymph leaving a node through its single efferent lymphatic vessel is enriched

with antibodies newly secreted by medullary plasma cells and also has a fiftyfold higher concentration of lymphocytes than the afferent lymph. The increase in lymphocytes in lymph leaving a node is due in part to lymphocyte proliferation within the node in response to antigen

References:

 Kuby, 5^th edition, Unit 2: Cells and organs of immune system, pg 47-48, Immunology.