Anatomy of the Immune System
Author(s): David Dorward, Genevieve McMahon and Hannah McManus
This CAL will cover the importance of the primary and secondary lymphoid organs, with a particular focus on the lymph nodes, which is the site of many antigen-immune cell interactions.
By the end of this section you should understand:
- the difference between primary and secondary lymphoid organs and their role in immunity
- the intricacies of the lymph node and how their structure contributes to functionality
Primary and secondary lymphoid organs Part 1 of 3
Cells of the immune system traffic through our bodies both in the blood and by using a specialised system of vessels called the lymphatics.
These are very similar in structure and function to blood vessels, but instead of carrying blood they carry a clear fluid called lymph.
Extracellular fluid is drained from the peripheral tissues into the lymphatic vessels, which carry it back to the thoracic duct, passing through lymph nodes along the way. This allows antigen presenting cells (APCs) and lymphocytes to interact if a foreign antigen is present. These cells are then returned to the blood via the left subclavian vein, to recirculate once more.
A lymphoid organ is a large network of aggregated lymphocytes contained within a non-lymphoid cell scaffold. These organs are categorised into primary and secondary organs.
Primary lymphoid organs
There are only two primary lymphoid organs – the thymus and the bone marrow (bursa analogue). These are the sites where immature T and B cells, respectively, mature before they leave to circulate through the body to interact with their cognate antigen in the secondary lymphoid organs.
The word cognate means that these antigens fit perfectly into a specific BCR or TCR, binding together very strongly to produce a firm bond. Just to be confusing, both T and B cells originate from the bone marrow; T cells then migrate to the thymus where they complete their development, whereas B cells remain.
Secondary lymphoid organs
Secondary lymphoid organs are also known as peripheral lymphoid organs. These are the sites that mature but naïve cells migrate to.
These organs facilitate the interaction between APCs and the mature naive lymphocytes as they circulate through the body. Not only are they good at trapping the cells, but they also help to propagate survival through signals from stromal cells.
APCs in the tissues collect antigen at the site of infection, and this causes them to upregulate certain receptors targeting them towards the secondary lymphoid organs, and therefore towards the lymphocytes. Once in the lymphoid organ, chemokine gradients attract them towards a certain area to initiate an adaptive immune response.
Secondary lymphoid organs include the spleen, lymph nodes and mucosal-associated tissues (MALT) of the gut, respiratory tract, urogenital tract and any other mucosal tissues.
In order for lymphocytes to reach the secondary lymphoid organ, they must escape the blood vessels, a process known as extravasation. To do this, they must interact with the high endothelial venules, or HEVs, using cell adhesion molecules on their cell surface – selectins and integrins. These vessels are venous swellings enabling lymphocytes to cross between blood and lymph nodes.
Lymph Nodes Part 2 of 3
Lymph nodes are secondary lymphoid organs which are found in places where lymphatic vessels converge. This means that they are very good at trapping APCs travelling from the surrounding tissues, which can then present antigen to circulating lymphocytes as they pass through.
The structure of a lymph node is very important, as it allows the interaction between the various immune cells necessary to mount an adaptive response if a foreign antigen is being presented.
The lymph node consists of:
- The afferent lymphatic vessels at the top are bringing lymph into the lymph node.
- The blue structures are follicles, where the B lymphocytes are found. These consists of a pale zone in the centre surrounded by a dark area around the outside.
- The pink area is the T cell zone, or paracortex, where the T lymphocytes localise.
- The innermost structure is the medulla, which contains sinusoids lined by macrophages. These phagocytose any material which has been carried into the lymph node through the afferent lymphatics and the peripheral sinus which they can then present to surrounding lymphocytes.
Chemokines are messenger proteins which attract cells depending on receptors that they express on their surface. The chemokines that attract a B cell are different to those that attract a T cell, allowing the lymph node to be split by cell type.
T cells express the receptor CCR7 which binds the chemokines CCL19 and CCL21. CCL21 is produced by the stromal cells lining the T cell zones, hence attracting the cells here. Dendritic cells present also produce CCL19 and CCL21 within the T cell zones, further encouraging the T cells to congregate here.
B cells, on the other hand, express the receptor CXCR5, binding CXCL13. This again is expressed by stromal and dendritic cells in the relevant B cell areas. There are also some funky cells called T follicular helper cells which also express CXCR5, allowing them to enter the B cell follicles and contribute to germinal centre formation. You can find out more about this here.
Conclusion Part 3 of 3
Cells of the immune system travel around the body using the blood and lymphatic systems. These vessels drain into lymph nodes which act as central locations where APCs and lymphocytes can interact, producing an immune reaction if a foreign antigen is present.
These lymph nodes are an example of a secondary lymphoid organ, trapping antigens and facilitating these interactions, particularly by using chemokine gradients to guide cells into particular areas of the structure.
Primary lymphoid organs, like the thymus and bone marrow, however, are responsible for the initial production and education of lymphocytes, prior to their migration around the body in search of foreign antigen.