The lymphatic system consists of a conducting network of lymphatic vessels, lymphoid organs, lymphoid tissues, and the circulating
lymph. The
thymus and the
bone marrow constitute the primary lymphoid organs involved in the production and early
clonal selection of lymphocyte tissues.
Bird species' primary lymphoid organs include the bone marrow, thymus,
bursa of Fabricius, and yolk sac.
Red bone marrow Bone marrow- specifically
red bone marrow- is responsible for both the creation of
T cell precursors and the production and maturation of
B cells, which are known as lymphocytes, important cell types of the immune system. From the red bone marrow, B cells immediately join the circulatory system and travel to secondary lymphoid organs in search of pathogens. T cells, on the other hand, travel from the bone marrow to the thymus, where they undergo a multistage process to develop immunocompetency. Within the
thymic cortex, developing T cells rearrange their T-cell receptor (TCR) genes and are subjected to
positive selection, which ensures that only T cells capable of recognizing self-
major histocompatibility complex (MHC) molecules survive. Those that bind too weakly die off. Surviving T cells then move to the
thymic medulla, where
negative selection removes T cells that bind self-antigens with high affinity, preventing autoimmune disorders. Less than 5% of T cells pass both selection tests and reach maturity; these mature T cells then join B cells in search of pathogens.
Thymus The thymus increases in size from birth in response to postnatal antigen stimulation. It is most active during the neonatal and pre-adolescent periods. The thymus is located between the inferior neck and the superior thorax. During adolescence, the thymus begins to atrophy and regress, with adipose tissue mostly replacing the thymic stroma. However, residual T cell lymphopoiesis continues throughout adulthood, providing some immune response. The thymus is where the T lymphocytes mature and become immunocompetent. The absence of the thymus (whether congenital or due to loss of the thymus gland) results in severe
immunodeficiency and subsequent high susceptibility to infection. In most species, the thymus consists of lobules divided by septa. These are composed of epithelium.
T cells mature from
thymocytes, proliferate, and undergo a selection process in the thymic cortex before entering the medulla to interact with epithelial cells. Research on
bony fish showed a buildup of T cells in the thymus and spleen of lymphoid tissues in
salmon and showed that there are not many T cells in non-lymphoid tissues. The thymus provides an inductive environment for developing T cells from hematopoietic progenitor cells. In addition, thymic stromal cells facilitate the selection of a functional and self-tolerant T cell repertoire. Therefore, one of the most important roles of the thymus is the induction of central tolerance. However, the thymus is not where the infection is fought, as the T cells have yet to become immunocompetent.
Secondary lymphoid organs The secondary (or peripheral) lymphoid organs, which include
lymph nodes and the
spleen, maintain mature naive lymphocytes and initiate an
adaptive immune response. The secondary lymphoid organs are the sites of lymphocyte activation by
antigens. Activation leads to
clonal selection and
affinity maturation. Mature lymphocytes recirculate between the blood and the secondary lymphoid organs until they encounter their specific antigen.
Spleen The main functions of the spleen are: • to produce
immune cells to fight
antigens, • to remove
particulate matter and aged blood cells, mainly
red blood cells, and • to produce blood cells during fetal life. The spleen synthesizes
antibodies in its
white pulp and removes antibody-coated bacteria and antibody-coated blood cells by way of blood and
lymph node circulation. The white pulp of the spleen provides immune function due to the lymphocytes housed there. The spleen also consists of red pulp, which is responsible for getting rid of aged red blood cells and pathogens. This is carried out by macrophages present in the red pulp. A study published in 2009 using mice found that the spleen contains, in its reserve, half of the body's
monocytes within the
red pulp. These monocytes, upon moving to injured tissue (e.g., the heart), turn into
dendritic cells and
macrophages while promoting tissue healing. The spleen is a center of activity of the
mononuclear phagocyte system. It can be considered analogous to a large lymph node, as its absence causes a predisposition to certain
infections. Notably, the spleen is essential for a multitude of functions. The spleen removes pathogens and old erythrocytes from the blood (red pulp) and produces lymphocytes for immune response (white pulp). The spleen is also responsible for recycling some erythrocyte components and discarding others. For example, hemoglobin is broken down into amino acids, which are reused. Research on
bony fish has shown that a high concentration of T cells is found in the spleen's white pulp. The
germinal centers are supplied by
arterioles called
penicilliary radicles. In humans, until the fifth month of
prenatal development, the spleen creates
red blood cells; after birth, the
bone marrow is solely responsible for
hematopoiesis. As a major lymphoid organ and a central player in the reticuloendothelial system, the spleen retains the ability to produce lymphocytes. The spleen stores
red blood cells and lymphocytes. It can store enough blood cells to help in an emergency. During acute blood loss, the spleen contracts to release stored erythrocytes, helping to maintain blood volume and oxygen delivery temporarily. Up to 25% of lymphocytes can be stored at any one time.
Lymph nodes and
efferent lymphatic vessels A
lymph node is an organized collection of lymphoid tissue through which the lymph passes on its way back to the blood. Lymph nodes are located at intervals along the lymphatic system. Several
afferent lymph vessels bring in lymph, which percolates through the substance of the lymph node and is then drained out by an
efferent lymph vessel. Of the nearly 800 lymph nodes in the human body, about 300 are located in the head and neck. Many are grouped in clusters in different regions, as in the underarm and abdominal areas. Lymph node clusters are commonly found at the proximal ends of limbs (e.g., groin or armpits) and in the neck, where lymph is collected from body regions likely to sustain pathogen contamination from injuries. Lymph nodes are particularly numerous in the
mediastinum in the chest, neck, pelvis,
axilla,
groin (or inguinal region), and in association with the blood vessels of the intestines. TLOs are often characterized by CD20+ B cell zone, which is surrounded by CD3+ T cell zone, similar to the lymph follicles in secondary lymphoid organs (SLOs) and are regulated differently from the normal process whereby lymphoid tissues are formed during
ontogeny, being dependent on
cytokines and
hematopoietic cells, but still drain
interstitial fluid and transport lymphocytes in response to the same chemical messengers and gradients. Mature TLOs often have an active
germinal center, surrounded by a network of
follicular dendritic cells (FDCs). Although the specific composition of TLOs may vary, within the T cell compartment, the dominant subset of T cells is CD4+ T follicular helper (TFH) cells, but certain number of
CD8+ cytotoxic T cells, CD4+ T helper 1 (TH1) cells, and
regulatory T cells (Tregs) can also be found within the T cell zone. TLOs typically contain far fewer lymphocytes, and assume an immune role only when challenged with
antigens that result in
inflammation. They achieve this by importing the lymphocytes from blood and lymph. According to the composition and activation status of the cells within the lymphoid structures, at least three organizational levels of TLOs have been described. The formation of TLOs starts with the aggregating of lymphoid cells and occasional DCs, but FDCs are lacking at this stage. The next stage is immature TLOs, also known as primary follicle-like TLS, which have an increased number of T cells and B cells with distinct T cell and B cell zones and the formation of FDCs network, but without germinal centres. Finally, fully mature (also known as secondary follicle-like) TLOs often have active germinal centres and
high endothelial venules (HEVs), demonstrating a functional capacity by promoting T cell and B cell activation and then leading to expansion of TLS through cell proliferation and recruitment. During TLS formation, T and B cells are separated into two distinct but adjacent zones, with some cells able to migrate from one to the other, which is a crucial step in developing an effective and coordinated immune response. TLOs may play a key role in the immune response to cancer and serve as a prognostic marker for immunotherapy. TLOs have been reported to present in different cancer types such as
melanoma,
non-small-cell lung cancer and
colorectal cancer (reviewed by Sautès-Fridman and colleagues in 2019), as well as
glioma. TLOs are also seen as a read-out of treatment efficacy. For example, in patients with pancreatic ductal adenocarcinoma (PDAC), vaccination led to the formation of TLOs in responders. Within these patients, lymphocytes in TLOs displayed an activated phenotype, and in vitro experiments showed their capacity to perform effector functions. even though certain cancer types showed an opposite effect. Besides, TLOs with an active
germinal center seem to show a better prognosis than those with TLOs without a germinal center.
Other lymphoid tissue Lymphoid tissue associated with the lymphatic system is concerned with immune functions in defending the body against
infections and the spread of
tumours. It consists of
connective tissue formed of
reticular fibers, with various types of
leukocytes (white blood cells), mostly
lymphocytes enmeshed in it, through which the lymph passes. Regions of the lymphoid tissue that are densely packed with lymphocytes are known as
lymphoid follicles. Lymphoid tissue can either be structurally well organized as lymph nodes or may consist of loosely organized lymphoid follicles known as the
mucosa-associated lymphoid tissue (MALT). The
central nervous system also has lymphatic vessels. The search for T cell gateways into and out of the
meninges uncovered functional
meningeal lymphatic vessels lining the
dural sinuses, anatomically integrated into the membrane surrounding the brain.
Lymphatic vessels The
lymphatic vessels, also called lymph vessels, are thin-walled vessels that conduct lymph between different parts of the body. They include the tubular vessels of the
lymph capillaries, and the larger collecting vessels – the
right lymphatic duct and the
thoracic duct (the left lymphatic duct). Lymph capillaries are primarily responsible for the absorption of interstitial fluid from the tissues. Lymph vessels propel the absorbed fluid forward into the larger collecting ducts, where it ultimately returns to the bloodstream via one of the
subclavian veins. The tissues of the lymphatic system are responsible for maintaining the balance of the
body fluids. Its network of capillaries and collecting lymphatic vessels efficiently drain and transport extravasated fluid, along with proteins and antigens, back to the circulatory system. Numerous intraluminal valves in the vessels ensure a unidirectional lymph flow without reflux. Two valve systems, a primary and a secondary valve system, are used to achieve this unidirectional flow. The capillaries are blind-ended; the valves at the ends of capillaries use specialised junctions together with anchoring filaments to allow a unidirectional flow to the primary vessels. When interstitial fluid increases, it causes swelling that stretches collagen fibers anchored to adjacent connective tissue, opening the unidirectional valves at the ends of these capillaries and facilitating the entry and subsequent drainage of excess lymph fluid. The collecting lymphatics, however, propel the lymph by the combined actions of the intraluminal valves and lymphatic muscle cells. ==Development==