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Secondary Lymphoid Organs and Lymphocyte Traffic


Secondary Lymphoid Organs And Lymphocyte Traffic
The ability to recirculate from blood to tissues and back through the lymphoid system is unique to lymphocytes and, coupled with their long lifespan and specificity for individual antigens, equips them for their central role in adaptive immune responses.

Secondary Lymphoid Organs And Lymphocyte Traffic

The thorough mixing of lymphocytes, particularly in the spleen and lymph nodes, ensures the maximum contact of antigen-presenting cells that have newly encountered antigen, with T and B lymphocytes potentially able to respond, which would otherwise be a very rare event. The body-wide dissemination of expanded T and B populations in readiness for a second encounter with the same antigen ensures that ‘memory’ is available at all sites.
Different types of lymphocyte ‘home’ to different regions in the lymphoid organs (T and B areas in the figure; B areas are shaded). This ‘lymphocyte traffic’ is regulated by a combination of chemotactic factors released from particular sites (mostly members of the chemokine family; see Fig. 7) and direct contact via adhesion receptors  (sometimes  known  as  ‘addressins’  because  they  direct lymphocytes to particular sites in the body) between lymphocytes and the extracellular matrix or other cells such as the inner surface of the vascular endothelium or the dendritic antigen-presenting cells (not shown here, but see Fig. 8). The introduction of a new form of fluorescent microscopy, known as two-photon microscopy, has allowed the visualization of lymphocyte movement within living lymphoid tissue.
In general, lymph nodes respond to antigens introduced into the tissues they drain, and the spleen responds to antigens in the blood. The gut, lungs, breast and external mucous surfaces also have their own less specialized lymphoid areas that to some extent behave as a separate circuit for recirculation purposes and are often known as the mucosa-associated lymphoid tissues (MALT). These can be further subdivided into gut-associated (GALT), bronchial-associated (BALT) and skin-associated (SALT) lymphoid tissue. In each case, the objective seems to be to provide a local lymphoid system specialized for the antigens most likely to be encountered there.
Lymph node
Lymph nodes (or ‘glands’) constitute the main bulk of the organized lymphoid tissue. They are strategically placed so that lymph from most parts of the body drains through a series of nodes before reaching the thoracic duct (TD), which empties into the left subclavian vein to allow the lymphocytes to recirculate again via the blood.
AL, EL Afferent and efferent lymphatics, through which lymph passes from the tissues to first peripheral and then central lymph nodes. The cells found in afferent and efferent lymph are quite different. Naïve T cells enter lymph nodes from blood, but then leave via the efferent lymphatics, before eventually rejoining the blood. Memory or effector T cells enter tissues at sites of infection, and then travel back to lymph nodes via the afferent lymphatics. Afferent lymph also carries antigen and dendritic cells (known as veiled cells while in lymph) as they migrate from tissues such as the skin to the T-cell areas of the lymph node.
S Lymphatic sinus, through which lymph flows from the afferent lymphatic into the cortical and medullary sinuses. The lymph carries antigens and antigen-presenting cells from tissues to lymphoid tissue, and a series of fine collagen tubes runs from the cortical sinus into the T-cell areas, facilitating the movement of antigens directly to the antigen-presenting dendritic cells.
M Medullary sinus, collecting lymph for exit via the efferent lymphatic. It is in the medulla that antibody formation takes place and plasma cells are prominent.
G Germinal centre; an area of rapidly dividing cells that develops within the follicle after antigenic stimulation. It is the site of B memory-cell generation, and contains special follicular dendritic cells that retain antigens on their surface for weeks and perhaps even years (for further details see Fig. 19).
T T-cell area, or ‘paracortex’, largely occupied by T cells but through which B cells travel to reach the medulla. The dendritic cells here are specialized for presentation of antigen to T cells, and are probably the site where T and B lymphocytes of the right specificity meet and cooperate, which would otherwise be a very rare event.
PCV Post-capillary venule; a specialized small venule with high cuboidal endothelium (known as a high endothelial venule [HEV]) through which lymphocytes leave the blood to enter the paracortex and thence the efferent lymphatic, ultimately returning to blood via the thoracic duct.
Spleen
The spleen differs from a lymph node in having no lymphatic drainage, and also in containing large numbers of red cells. In some species it can act as an erythropoietic organ or a reservoir for blood.
T T-cell area; the lymphoid sheath surrounding the arteries is mostly composed of T lymphocytes.
B B-cell area, or lymphoid follicle, typically lying to one side of the lymphoid sheath. Germinal centres are commonly found in the follicle, alongside the follicular artery.
MZ Marginal zone; the region between the lymphoid areas and the red pulp, where lymphocytes chiefly leave the blood to enter the lymphoid areas, and red cells and plasma cells enter the red pulp.
RP Red pulp; a reticular meshwork through which blood passes to enter the venous sinusoids, and in which surveillance and removal of damaged red cells is thought to occur. For contrast, the lymphoid areas are some-times called ‘white pulp’. Macrophages in the red pulp and in the marginal zone can retain antigens, as the dendritic cells in the lymph nodes do. As in the medulla of the lymph node, plasma cells are frequent.
S Sinusoids; the large sacs that collect blood for return via the splenic vein.

Mucosa-associated lymphoid tissues
At least 50% of all tissue lymphocytes are associated with mucosal surfaces, emphasizing that these are the main sites of entry of foreign material. It is estimated that the total area of mucosal surfaces is 400 times that of the body, and that the number of bacteria colonizing these surfaces is many times more than the total number of cells in the body.
Gut The GALT is composed of two types of tissue: organized and diffuse. Typical organized tissues are the lymphoid aggregates, e.g. the Peyer’s patches analogous to the lymphoid follicles in lymph nodes. The transfer of antigens from the gut lumen to the subepithelial area occurs via specialized M (membrane) cells, which pass them to dendritic cells where they are presented to T and B cells in the normal way. However, dendritic cells within the epithelium may also extend processes between the epithelial cells and take up antigens directly from the gut lumen. Although the ability to take up antigens is important in starting an adaptive immune response, some pathogens (e.g. HIV, Sal- monella) may use this ‘Trojan horse’ route to invade their hosts.
Most of the B cells are specialized for IgA production, and B-cell memory develops in germinal centres. Cells that leave the follicles circulate in the blood to the diffuse lymphoid areas in the lamina propria, where large numbers of IgA plasma cells are found, as well as CD8+ γδ T cells, NK cells and mast cells. This preferential homing of MALT cells to MALT sites is mediated by specialized surface molecules on the lymphocytes and on the endothelium of blood vessel walls.
IgA Lamina propria B cells are responsible for the majority of IgA antibody, although a small amount is made in other sites such as bone marrow. IgA occurs mainly as dimers of two molecules held together by a J (joining) chain (see Fig. 14). IgA is protected against proteolytic digestion by a polypeptide secretory piece derived from the poly-Ig receptor and added to the IgA dimers in the epithelial cells.
Pharynx Lymphoid aggregates are prominent at this vulnerable site (tonsil and adenoids). The salivary glands also contain lymphocytes of MALT origin.
Lung The lung alveoli are largely protected from inhaled antigens by the upward movement of mucus propelled by beating cilia and ultimately coughed up or swallowed (the ‘mucociliary escalator’). Organized and diffuse lymphoid tissues are present in the walls of the bronchi (the upper respiratory tract) but are absent from the lung alveoli (the lower respiratory tract). However, alveoli contain large numbers of alveolar macrophages that take up any debris or microorganisms that reach them. Alveolar macrophages can rapidly recruit T lymphocytes if an infection develops.
Skin Antigens entering via the skin can reach the local lymph node by being taken up in Langerhans’ cells (LC) or dermal dendritic cells, which then can pass from the skin to the node, where they settle in the T-cell areas. Alternatively, soluble antigens can travel directly via the lymphatics to the draining lymph nodes. The skin also contains specialized populations of T cells that have a rather limited range of specificities and may act as an initial barrier to infection.