(3) Germinal centers appear 3-5 days after infection: Nodules with germinal centers (secondary nodules) appear 4-5 days after introduction of foreign antigen and may remain for several days. During this time plasma cells begin to settle between the sinusoids of the medulla to form medullary cords. Other activated B cell progeny and activated T cell progeny percolate through the lymph node and exit via the efferent lymphatic vessels to spread to other lymphatic tissues and eventually the blood circulation. Thus, most memory and effector T cells and some memory B cells eventually re-enter the general blood circulation but effector B-cells (plasmablasts and plasma cells) are retained within the lymph node.
Figure 6. Time course of an immunological response within a lymph node. See text for details. (Redrawn from Hood, Weissman, and Wood. Immunology).
(4) Lymph node swells 6-8 days after infection: Activated T and B cells also release soluble factors that cause local blood vessels to dilate allowing leakage of plasma into the lymph node. Some of these factors attract macrophages while other factors retain lymphocytes within the node. The resulting accumulation of cells and fluid may plug the medullary sinusoids leading to the efferent lymphatic vessel. As a consequence, the lymph node enlarges rapidly causing the typical “swollen glands” of infection.
(5) The node returns to its original size only as the response to infection abates.
All lymphatic tissues except the thymus are part of a surveillance system in which lymphocytes migrate from the blood stream into interstitial space, then into lymphatic vessels and return to the blood stream via the right lymphatic duct and thoracic duct. This is a slow process taking 4-6 hours not a mass migration. This path can be short circuited in lymph nodes and in other lymphatic tissues, such as the tonsils, Peyer’s patches, and MALT, at HEVs, where T and B lymphocytes can move quickly from blood into lymphatic drainage often in large numbers (Fig. 7). As a consequence of this migration, antigens throughout the body are examined and specific lymphocytes can be activated even though they are located far from the original invasion. In general, T lymphocytes are circulating while B lymphocytes tend to reside in the spleen, lymph nodes, and Peyer’s Patches.
Figure 7. Pathway of lymphocyte circulation. [Redrawn from J.L. Gowan’s Hosp. Pract.].
Does the lymphatic drainage deliver only lymphocytes to the blood circulation? No. Lymphatic drainage also provides a route for distributing pathogens and cancer cells. If these cells evade detection and removal in the lymph node, then they are delivered to the blood circulation (by thoracic duct or right lymphatic duct) for distribution throughout the body. Metastasis to the regional lymph node from lymphatic vessels draining an organ (or tissue) is a common step in the progression of many cancers (e.g., breast and prostate) and is an important prognostic indicator.
The spleen is a complex filter interposed in the blood stream that does two jobs:
(a) Removal of particulate matter and senescent red blood cells
(b) Immune response to blood-borne antigens such as bacteria and protozoa.
The spleen is a compact organ encased by a capsule of dense irregular connective tissue covered by a mesothelium. Multiple branching trabeculae extend into the organ from the capsule. These trabeculae, in turn are connected to a network of reticular cells and reticular fibers that support the parenchyma.
The parenchyma is referred to as splenic pulp. In the freshly dissected non-perfused spleen, the splenic pulp appears white and red (Fig. 8).
White pulp consists of lymphocytes organized into large nodules (called follicles) and diffuse lymphatic tissue separated from the red pulp by a relatively acellular region called the marginal zone. The white pulp is responsible for most of the immunological function of the spleen.
Red pulp consists of a large number of sinuses filled with erythrocytes separated by a reticulum of cells called the Cords of Billroth. The red pulp is responsible for the filtration function of the spleen.