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Lymph node
Lymph node
Lymph node
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Lymph node
Diagram showing major parts of a lymph node
Lymph nodes form part of the lymphatic system, and are present in most parts of the body, and connected by small lymphatic vessels.
Details
SystemLymphatic system, part of the immune system
Identifiers
Latinnodus lymphaticus (singular); nodi lymphatici (plural)
MeSHD008198
TA98A13.2.03.001
TA25192
FMA5034
Anatomical terminology

A lymph node, or lymph gland,[1] is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include B and T cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles including cancer cells, but have no detoxification function.

In the lymphatic system, a lymph node is a secondary lymphoid organ. A lymph node is enclosed in a fibrous capsule and is made up of an outer cortex and an inner medulla.

Lymph nodes become inflamed or enlarged in various diseases, which may range from trivial throat infections to life-threatening cancers. The condition of lymph nodes is very important in cancer staging, which decides the treatment to be used and determines the prognosis. Lymphadenopathy refers to glands that are enlarged or swollen. When inflamed or enlarged, lymph nodes can be firm or tender.

Structure

[edit]
Cross-section of a lymph node with sections labelled.1) Capsule; 2) Subcapsular sinus; 3) Germinal center; 4) Lymphoid nodule; 5) Trabeculae

Lymph nodes are kidney or oval shaped and range in size from 2 mm to 25 mm on their long axis, with an average of 15 mm.[2]

Each lymph node is surrounded by a fibrous capsule (made of collagenous connective tissue),[3] which extends inside the lymph node to form trabeculae.[4] The substance of a lymph node is divided into the outer cortex and the inner medulla.[4] These are rich with cells.[5] The hilum is an indent on the concave surface of the lymph node where lymphatic vessels leave and blood vessels enter and leave.[5]

Lymph enters the convex side of a lymph node through multiple afferent lymphatic vessels, and from there, it flows into a series of sinuses. Upon entering the lymph node, lymph first passes into a space beneath the capsule known as the subcapsular sinus, then moves into the cortical sinuses. After traversing the cortex, lymph collects in the medullary sinuses. Finally, all of these sinuses drain into the efferent lymphatic vessels, which carry the lymph away from the node, exiting at the hilum on the concave side.

Location

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See also: List of lymph nodes of the human body

Lymph nodes are present throughout the body, are more concentrated near and within the trunk, and are divided into groups.[5] There are about 450 lymph nodes in the adult.[5] Some lymph nodes can be felt when enlarged (and occasionally when not), such as the axillary lymph nodes under the arm, the cervical lymph nodes of the head and neck and the inguinal lymph nodes near the groin crease. Most lymph nodes lie within the trunk adjacent to other major structures in the body - such as the paraaortic lymph nodes and the tracheobronchial lymph nodes. The lymphatic drainage patterns are different from person to person and even asymmetrical on each side of the same body.[6][7]

There are no lymph nodes in the central nervous system, which is separated from the body by the blood–brain barrier. Lymph from the meningeal lymphatic vessels in the CNS drains to the deep cervical lymph nodes.[8] However, the CNS does innervate lymph node by sympathetic nerves. These regulate lymphocyte proliferation and migration, antibody secretion, blood perfusion, and inflammatory cytokine production.[9]

Size

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Upper limit of lymph node sizes in adults
Generally 10 mm[10][11]
Inguinal 10[12] – 20 mm[13]
Pelvis 10 mm for ovoid lymph nodes, 8 mm for rounded[12]
Neck
Generally (non-retropharyngeal) 10 mm[12][14]
Jugulodigastric lymph nodes 11mm[12] or 15 mm[14]
Retropharyngeal 8 mm[14]
  • Lateral retropharyngeal: 5 mm[12]
Mediastinum
Mediastinum, generally 10 mm[12]
Superior mediastinum and high paratracheal 7mm[15]
Low paratracheal and subcarinal 11 mm[15]
Upper abdominal
Retrocrural space 6 mm[16]
Paracardiac 8 mm[16]
Gastrohepatic ligament 8 mm[16]
Upper paraaortic region 9 mm[16]
Portacaval space 10 mm[16]
Porta hepatis 7 mm[16]
Lower paraaortic region 11 mm[16]

Subdivisions

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Histology of a normal lymphoid follicle, showing dark, light, mantle and marginal zones

A lymph node is divided into compartments called nodules (or lobules), each consisting of a region of cortex with combined follicle B cells, a paracortex of T cells, and a part of the nodule in the medulla.[17] The substance of a lymph node is divided into the outer cortex and the inner medulla.[4] The cortex of a lymph node is the outer portion of the node, underneath the capsule and the subcapsular sinus.[17] It has an outer part and a deeper part known as the paracortex.[17] The outer cortex consists of groups of mainly inactivated B cells called follicles.[5] When activated, these may develop into what is called a germinal center.[5] The deeper paracortex mainly consists of the T cells.[5] Here the T-cells mainly interact with dendritic cells, and the reticular network is dense.[18]

The medulla contains large blood vessels, sinuses and medullary cords that contain antibody-secreting plasma cells. There are fewer cells in the medulla.[5]

The medullary cords are cords of lymphatic tissue, and include plasma cells, macrophages, and B cells.

Cells

[edit]

In the lymphatic system a lymph node is a secondary lymphoid organ.[5] Lymph nodes contain lymphocytes, a type of white blood cell, and are primarily made up of B cells and T cells.[5] B cells are mainly found in the outer cortex where they are clustered together as follicular B cells in lymphoid follicles, and T cells and dendritic cells are mainly found in the paracortex.[19]

There are fewer cells in the medulla than the cortex.[5] The medulla contains plasma cells, as well as macrophages which are present within the medullary sinuses.[19] In case of diseases like cancer, macrophages within the lymph nodes may play pro-cancerous role by deleting anticancer T cells e.g., PD-L1+ macrophages in lymph nodes, facilitated by anticancer vaccines, can directly delete CD8+ T cells via extrinsinc apoptotic signalling.[20]

As part of the reticular network, there are follicular dendritic cells in the B cell follicle and fibroblastic reticular cells in the T cell cortex. The reticular network provides structural support and a surface for adhesion of the dendritic cells, macrophages and lymphocytes. It also allows exchange of material with blood through the high endothelial venules and provides the growth and regulatory factors necessary for activation and maturation of immune cells.[21]

Lymph flow

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Human lymph node
Labeled diagram of human lymph node showing the flow of lymph
Afferent and efferent vessels

Lymph enters the convex side of a lymph node through multiple afferent lymphatic vessels, which form a network of lymphatic vessels (Latin: plexus) and flows into a space (Latin: sinus) underneath the capsule called the subcapsular sinus.[5][4] From here, lymph flows into sinuses within the cortex.[4] After passing through the cortex, lymph then collects in medullary sinuses.[4] All of these sinuses drain into the efferent lymphatic vessels to exit the node at the hilum on the concave side.[4]

These are channels within the node lined by endothelial cells along with fibroblastic reticular cells, allowing for the smooth flow of lymph. The endothelium of the subcapsular sinus is continuous with that of the afferent lymph vessel and also with that of the similar sinuses flanking the trabeculae and within the cortex. These vessels are smaller and do not allow the passage of macrophages so that they remain contained to function within a lymph node. In the course of the lymph, lymphocytes may be activated as part of the adaptive immune response.

There is usually only one efferent vessel though sometimes there may be two, in contrast to the multiple afferent channels that bring lymph into the node.[22] Medullary sinuses contain histiocytes (immobile macrophages) and reticular cells, the former of which, along with T and B cells, become activated in the presence of antigens through lymphatic flow. The fewer efferent vessels allow this flow to be slowed, providing time to activate and distribute a larger number of immune cells in the event of an infection.

A lymph node contains lymphoid tissue, i.e., a meshwork or fibers called reticulum with white blood cells enmeshed in it. The regions where there are few cells within the meshwork are known as lymph sinus. It is lined by reticular cells, fibroblasts and fixed macrophages.[23]

Capsule

[edit]
Lymph node tissue showing trabeculae

Thin reticular fibers (reticulin) of reticular connective tissue form a supporting meshwork inside the node.[5] These reticular cells also form a conduit network within the lymph node that functions as a molecular sieve, to prevent pathogens that enter the lymph node through afferent vessels re-enter the blood stream.[24] The lymph node capsule is composed of dense irregular connective tissue with some plain collagenous fibers, and a number of membranous processes or trabeculae extend from its internal surface. The trabeculae pass inward, radiating toward the center of the node, for about one-third or one-fourth of the space between the circumference and the center of the node. In some animals they are sufficiently well-marked to divide the peripheral or cortical portion of the node into a number of compartments (nodules), but in humans this arrangement is not obvious. The larger trabeculae springing from the capsule break up into finer bands, and these interlace to form a mesh-work in the central or medullary portion of the node. These trabecular spaces formed by the interlacing trabeculae contain the proper lymph node substance or lymphoid tissue. The node pulp does not, however, completely fill the spaces, but leaves between its outer margin and the enclosing trabeculae a channel or space of uniform width throughout. This is termed the subcapsular sinus (lymph path or lymph sinus). Running across it are a number of finer trabeculae of reticular fibers, mostly covered by ramifying cells.

Inverted lymph nodes

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Some mammal species, such as pigs, rhinoceroses, hippopotamuses, and certain cetaceans, have so-called "inverted" lymph nodes. In these nodes, the afferent lymph carries antigens from the center (where the B-cell follicles are located) toward the periphery. Mature B and T lymphocytes exit the lymph node from its periphery directly into the general bloodstream via efferent venules. These structural differences do not appear to impact the functionality of the lymph nodes.[25][26]

Function

[edit]
Main article: Lymphatic system

In the lymphatic system, a lymph node is a secondary lymphoid organ.[5]

Diagram of a lymph node showing lymphocytes

The primary function of lymph nodes is the filtering of lymph to identify and fight infection. In order to do this, lymph nodes contain lymphocytes, a type of white blood cell, which includes B cells and T cells. These circulate through the bloodstream and enter and reside in lymph nodes.[27] B cells produce antibodies. Each antibody has a single predetermined target, an antigen, that it can bind to. These circulate throughout the bloodstream and if they find this target, the antibodies bind to it and stimulate an immune response. Each B cell produces different antibodies, and this process is driven in lymph nodes. B cells enter the bloodstream as "naive" cells produced in bone marrow. After entering a lymph node, they then enter a lymphoid follicle, where they multiply and divide, each producing a different antibody. If a cell is stimulated, it will go on to produce more antibodies (a plasma cell) or act as a memory cell to help the body fight future infection.[28] If a cell is not stimulated, it will undergo apoptosis and die.[28]

Antigens are molecules found on bacterial cell walls, chemical substances secreted from bacteria, or sometimes even molecules present in body tissue itself. These are taken up by cells throughout the body called antigen-presenting cells, such as dendritic cells.[29] These antigen presenting cells enter the lymph system and then lymph nodes. They present the antigen to T cells and, if there is a T cell with the appropriate T cell receptor, it will be activated.[28]

B cells acquire antigen directly from the afferent lymph. If a B cell binds its cognate antigen it will be activated. Some B cells will immediately develop into antibody secreting plasma cells, and secrete IgM. Other B cells will internalize the antigen and present it to follicular helper T cells on the B and T cell zone interface. If a cognate FTh cell is found it will upregulate CD40L and promote somatic hypermutation and isotype class switching of the B cell, increasing its antigen binding affinity and changing its effector function. Proliferation of cells within a lymph node will make the node expand.

Lymph is present throughout the body, and circulates through lymphatic vessels. These drain into and from lymph nodes – afferent vessels drain into nodes, and efferent vessels from nodes. When lymph fluid enters a node, it drains into the node just beneath the capsule in a space called the subcapsular sinus. The subcapsular sinus drains into trabecular sinuses and finally into medullary sinuses. The sinus space is criss-crossed by the pseudopods of macrophages, which act to trap foreign particles and filter the lymph. The medullary sinuses converge at the hilum and lymph then leaves the lymph node via the efferent lymphatic vessel towards either a more central lymph node or ultimately for drainage into a central venous subclavian blood vessel.

  • The B cells migrate to the nodular cortex and medulla.
  • The T cells migrate to the deep cortex. This is a region of a lymph node called the paracortex that immediately surrounds the medulla. Because both naive T cells and dendritic cells express CCR7, they are drawn into the paracortex by the same chemotactic factors, increasing the chance of T cell activation. Both B and T lymphocytes enter lymph nodes from circulating blood through specialized high endothelial venules found in the paracortex.

Clinical significance

[edit]

Swelling

[edit]
A still image from a 3D medical animation showing enlarged lymph nodes
Main article: Lymphadenopathy

Lymph node enlargement or swelling is known as lymphadenopathy.[30] Swelling may be due to many causes, including infections, tumors, autoimmune disease, drug reactions, diseases such as amyloidosis and sarcoidosis, or because of lymphoma or leukemia.[31][30] Depending on the cause, swelling may be painful, particularly if the expansion is rapid and due to an infection or inflammation.[30] Lymph node enlargement may be localized to an area, which might suggest a local source of infection or a tumour in that area that has spread to the lymph node.[30] It may also be generalized, which might suggest infection, connective tissue or autoimmune disease, or a malignancy of blood cells such as a lymphoma or leukemia.[30] Rarely, depending on location, lymph node enlargement may cause problems such as difficulty breathing, or compression of a blood vessel (for example, superior vena cava obstruction[32]).

Enlarged lymph nodes might be felt as part of a medical examination, or found on medical imaging.[33] Features of the medical history may point to the cause, such as the speed of onset of swelling, pain, and other constitutional symptoms such as fevers or weight loss.[34] For example, a tumour of the breast may result in swelling of the lymph nodes under the arms[30] and weight loss and night sweats may suggest a malignancy such as lymphoma.[30]

In addition to a medical exam by a medical practitioner, medical tests may include blood tests and scans may be needed to further examine the cause.[30] A biopsy of a lymph node may also be needed.[30]

Cancer

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Micrograph of a mesenteric lymph node with adenocarcinoma

Lymph nodes can be affected by both primary cancers of lymph tissue, and secondary cancers affecting other parts of the body. Primary cancers of lymph tissue are called lymphomas and include Hodgkin lymphoma and non-Hodgkin lymphoma.[35] Cancer of lymph nodes can cause a wide range of symptoms from painless long-term slowly growing swelling to sudden, rapid enlargement over days or weeks, with symptoms depending on the grade of the tumour.[35] Most lymphomas are tumours of B-cells.[35] Lymphoma is managed by haematologists and oncologists.

Local cancer in many parts of the body can cause lymph nodes to enlarge because of tumorous cells that have metastasised into the node.[36] Lymph node involvement is often a key part in the diagnosis and treatment of cancer, acting as "sentinels" of local disease, incorporated into TNM staging and other cancer staging systems. As part of the investigations or workup for cancer, lymph nodes may be imaged or even surgically removed. If removed, the lymph node will be stained and examined under a microscope by a pathologist to determine if there is evidence of cells that appear cancerous (i.e. have metastasized into the node). The staging of the cancer, and therefore the treatment approach and prognosis, is predicated on the presence of node metastases.

Lymphedema

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Lymphedema is the condition of swelling (edema) of tissue relating to insufficient clearance by the lymphatic system.[37] It can be congenital as a result usually of undeveloped or absent lymph nodes, and is known as primary lymphedema. Lymphedema most commonly arises in the arms or legs, but can also occur in the chest wall, genitals, neck, and abdomen.[38] Secondary lymphedema usually results from the removal of lymph nodes during breast cancer surgery or from other damaging treatments such as radiation. It can also be caused by some parasitic infections. Affected tissues are at a great risk of infection.[citation needed] Management of lymphedema may include advice to lose weight, exercise, keep the affected limb moist, and compress the affected area.[37] Sometimes surgical management is also considered.[37]

Similar lymphoid organs

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The spleen and the tonsils are the larger secondary lymphoid organs that serve somewhat similar functions to lymph nodes, though the spleen filters blood cells rather than lymph. The tonsils are sometimes erroneously referred to as lymph nodes. Although the tonsils and lymph nodes do share certain characteristics, there are also many important differences between them, such as their location, structure and size.[39] Furthermore, the tonsils filter tissue fluid whereas lymph nodes filter lymph.[39]

The appendix contains lymphoid tissue and is therefore believed to play a role not only in the digestive system, but also in the immune system.[40]

See also

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References

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Bibliography

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Lymph node

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from Grokipedia
A lymph node is a small, bean-shaped structure that is a key component of the , functioning primarily to filter fluid from tissues, trap pathogens and abnormal cells, and facilitate immune responses by housing lymphocytes and other immune cells. These nodes, typically 1 to 2 cm in size, are distributed throughout the body in clusters, with approximately 600 to 800 present in an adult human, concentrated in areas such as the , armpits, , chest, and . They receive via afferent vessels, process it through internal sinuses and compartments, and return filtered fluid to the bloodstream via efferent vessels, thereby maintaining and preventing the spread of infections or malignancies. Structurally, each lymph node is encapsulated by a fibrous layer and divided into distinct regions: the outer cortex containing B-cell follicles for antibody production, the paracortex rich in T-cells for , and the inner medulla with cords and sinuses for further filtration by macrophages. High endothelial venules within the node allow circulating lymphocytes to enter and interact with antigens, enabling the activation of adaptive immune responses. Blood supply to the node supports these cellular activities, with arteries and veins ensuring nutrient delivery and waste removal. Lymph nodes play a vital role in both innate and adaptive immunity by engulfing and destroying , viruses, and debris through , while also initiating the production of antibodies and memory cells upon detecting threats. In clinical contexts, enlarged or tender lymph nodes often signal infections, autoimmune conditions, or cancers like , serving as diagnostic indicators through or imaging. Their strategic placement along lymphatic drainage pathways allows them to act as sentinel checkpoints, protecting specific body regions from systemic spread of disease.

Anatomy

Location and distribution

Lymph nodes are secondary lymphoid organs distributed throughout the body, strategically positioned to intercept and filter from various tissues before it returns to the bloodstream. In adults, there are approximately 600 to 800 lymph nodes, with the exact number varying by individual due to factors such as age and status. These nodes are organized into clusters primarily in the cervical (neck), axillary (armpit), inguinal (), mediastinal (chest), abdominal, and pelvic regions, where they align along the pathways of lymphatic vessels and major blood vessels to facilitate efficient drainage. The distribution of lymph nodes can be broadly categorized into superficial and deep groups. Superficial nodes are located in subcutaneous tissues and are more accessible, such as those in the cervical chain along the external jugular vein or the inguinal nodes below the inguinal ligament; these drain skin and superficial structures. In contrast, deep nodes are embedded within deeper tissues, often accompanying major arteries and veins, including the deep cervical nodes along the internal jugular vein, mediastinal nodes in the thoracic cavity, and iliac nodes in the pelvis; these handle drainage from internal organs and muscles. This superficial-deep organization reflects the parallel structure of the lymphatic system, which mirrors the venous network while providing complementary drainage./19%3A_Lymphatic_System/19.2%3A_Lymphatic_Vessels/19.2B%3A_Distribution_of_Lymphatic_Vessels) Functionally, lymph nodes are grouped into drainage pathways specific to organs or regions, with sentinel nodes serving as the initial filters in these routes—for example, axillary sentinel nodes for tissue or inguinal ones for lower limb structures. This arrangement ensures that lymph from peripheral sites flows through sequential node clusters toward central ducts, integrating with the broader for systemic circulation.

Size and morphology

Lymph nodes in humans are typically small, ovoid or bean-shaped structures measuring 0.5 to 2 cm in their longest dimension during rest, with a normal long axis generally not exceeding 1 cm. They exhibit a reniform (kidney-like) morphology, featuring a convex outer surface and a concave hilum where blood vessels and lymphatics enter and exit. This shape facilitates efficient lymph filtration and is consistent across most regional nodes, though size can vary slightly by location; for instance, inguinal nodes may reach up to 2.5 cm due to higher drainage volumes. Morphological variations exist across mammalian species, with nodes being distinctly ovoid and encapsulated in . In such as mice and rats, lymph nodes are similarly ovoid but proportionally smaller relative to body size, often displaying more pronounced medullary sinuses and differences in afferent drainage patterns compared to humans. These comparative traits highlight evolutionary adaptations in lymphoid organization while maintaining core structural similarities for immune function. On gross examination, normal lymph nodes possess a soft yet elastic consistency, allowing without undue firmness, and a glistening cut surface that appears gray-tan in color. This texture reflects their composition of lymphoid tissue supported by a fibrous capsule, contributing to resilience during immune . Age-related changes influence lymph node dimensions and structure, with nodes in children typically smaller than in adults, often under 1 cm in diameter in non-reactive states. In the elderly, nodes may undergo , resulting in reduced size, increased , and fat replacement, which diminishes overall lymphoid volume. These alterations underscore the dynamic nature of nodal morphology across the lifespan.

Capsule and external features

The capsule of a lymph node is composed of dense fibrous containing collagenous fibers, forming a tough outer layer that encloses the entire structure. This capsule is continuous with internal trabeculae, which are extensions of the same that radiate inward to provide structural support and compartmentalization within the node. Externally, lymph nodes exhibit a characteristic hilum, an indented region typically located on the medial side, serving as the primary site for the entry and exit of vessels. Multiple afferent lymphatic vessels penetrate the capsule near the hilum to deliver unfiltered into the subcapsular sinus, while one to two efferent lymphatic vessels exit from the hilum to carry filtered away. Additionally, an enters and a exits through the hilum, often terminating in high endothelial venules that facilitate trafficking. The capsule functions as a protective barrier, shielding the lymph node from mechanical stress encountered during flow and body movement, while also helping to contain potential pathogens and prevent their extracapsular dissemination. This structural integrity maintains the node's role in immune surveillance without compromising vascular or lymphatic access.

Internal subdivisions

Lymph nodes are internally compartmentalized into distinct zones that facilitate organized flow and immune processing. The outermost region is the cortex, a peripheral layer rich in B cells and characterized by lymphoid follicles, which may be primary (dense aggregates of small lymphocytes) or secondary (featuring germinal centers during active responses). Beneath the cortex lies the paracortex, a deeper zone primarily supporting T-cell functions through interactions with antigen-presenting cells. The innermost medulla consists of loosely arranged cords and sinuses oriented toward the hilum, where efferent vessels exit. Lymph enters the node via the subcortical sinus, a spacious channel located just beneath the capsule and above the cortex, which receives fluid from afferent lymphatics and distributes it inward through trabecular connections. This sinus is lined by endothelial cells and supported by a network of fibers, allowing lymph to percolate slowly while exposing it to resident cells. In the medulla, linear medullary cords extend parallel to the hilum, interspersed with medullary sinuses that collect lymph from upstream cortical and trabecular pathways before channeling it into efferent lymphatics. These cords represent specialized compartments for production and cellular output, while the sinuses ensure efficient drainage. The structural integrity of these subdivisions is maintained by a framework of reticular fibers, composed of type III and produced by reticular cells, which form a delicate meshwork throughout the sinuses and to support cellular migration and lymph filtration. These zones are populated by various immune cells, with the cortex favoring B cells, the paracortex T cells, and the medulla plasma cells, as detailed in the cellular composition section.

Cellular composition

Lymph nodes are primarily composed of lymphocytes, which form the bulk of their cellular and are organized in distinct zones. B lymphocytes (B cells) are concentrated in the cortical follicles, where they form primary follicles in resting states or secondary follicles with germinal centers during immune activation. These B cells constitute approximately 40% of the total lymphocytes in human lymph nodes. T lymphocytes (T cells) predominate in the paracortical region, comprising the remaining 60% of lymphocytes, and are further subdivided into CD4+ helper T cells and CD8+ cytotoxic T cells that interact closely within this T cell zone. Antigen-presenting cells, essential for initiating immune responses, include dendritic cells and macrophages. Dendritic cells are mainly located in the paracortex, where they capture and process antigens before presenting them to T cells via molecules. Macrophages reside primarily in the subcapsular, cortical, trabecular, and medullary sinuses, where they phagocytose pathogens, debris, and apoptotic cells from incoming . Supporting cells provide the structural framework for lymph node architecture and include reticular cells and fibroblasts. Reticular cells form a network of fibers throughout the node, particularly in the cortex and paracortex, creating conduits for lymph flow and supporting lymphocyte migration. Fibroblasts contribute to the stromal connective tissue, including the capsule and trabeculae, maintaining overall tissue integrity. High endothelial venules (HEVs) are specialized postcapillary venules lined with cuboidal endothelial cells, primarily found in the paracortex and medulla. These structures express adhesion molecules such as peripheral lymph node addressin (PNAd) and like CCL19 and CCL21, enabling the high-affinity entry of naïve lymphocytes from the bloodstream into the lymph node . The zonal distribution of these cell types aligns with the internal subdivisions of the lymph node, optimizing immune cell interactions.

Development and histology

Embryonic development

The embryonic development of lymph nodes originates from the lymphatic system's primordia, which arise during early human gestation. Around the 6th to 8th gestational week, endothelial buds sprout from the anterior and posterior cardinal veins, forming the initial lymph sacs or anlagen that serve as precursors to the lymphatic vasculature and nodes. These structures develop from mesenchymal tissue, with lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3, along with Prox1 transcription factor expression in venous endothelium, guiding the specification and budding of lymphatic endothelial cells. By the 9th to 11th weeks, these lymph sacs begin to anastomose into a primitive network, and mesenchymal cells invade them to establish the stromal framework, capsule, and connective tissue that delineate the emerging lymph node primordia. Lymphoid colonization of these primordia occurs progressively as the nodes take shape. Hematopoietic stem cells and lymphoid progenitors, originating from intraembryonic sites like the aorta-gonad-mesonephros , begin seeding the developing nodes around the 11th to 12th weeks, with significant lymphocytic infiltration intensifying by the 12th to 14th week. Lymphoid tissue inducer (LTi) cells, derived from these hematopoietic lineages, interact with stromal organizer cells via lymphotoxin signaling to promote clustering and compartmentalization, leading to the formation of rudimentary T-cell and B-cell zones by mid-gestation (around 11-14 weeks). Small lymphocytes, including T cells, populate the paracortex, while initial B-cell aggregates appear in the outer cortex, marking the onset of immune surveillance capabilities within the nodes. Node maturation continues through late and into postnatal life. By 15-17 weeks, subcapsular sinuses and early vascular patterns emerge, with corticomedullary differentiation becoming evident by 25-38 weeks, establishing the basic architectural subdivisions. However, full development of secondary follicles and germinal centers, essential for affinity maturation and responses, occurs postnatally in response to antigenic exposure and microbial colonization, driven by the influx of mature B and T cells and the differentiation of . This process remodels the nodal stroma, expanding the conduit network and enhancing transport and presentation functions.

Histological organization

The histological organization of lymph nodes reveals a compartmentalized structure optimized for immune interactions, consisting of a cortex, paracortex, and medulla, all supported by a reticular stroma. Under hematoxylin and (H&E) , the general architecture appears with a thin fibrous capsule enclosing subcapsular and trabecular sinuses that channel flow, while the cortex displays densely packed lymphocytes in follicles and the paracortex shows a more diffuse T-cell-rich zone. (IHC) further delineates cell populations, with markers such as and highlighting B cells in follicles, CD3 and CD5 identifying T cells in the paracortex, and CD10 marking B cells. In activated lymph nodes, secondary follicles within the cortex feature prominent germinal centers, which under H&E staining exhibit a pale-staining central area surrounded by a darker of small lymphocytes, often displaying a "" pattern due to scattered tingible body macrophages. These macrophages, characterized by abundant filled with phagocytosed apoptotic debris, are crucial for clearing cellular remnants during B-cell proliferation and selection. The germinal centers contain proliferating centroblasts in a dark zone and selected centrocytes in a light zone, with retaining antigens on their surfaces. The stromal framework, visualized via silver staining or IHC for reticular fibers, comprises a network of fibroblastic reticular cells (FRCs) producing type III collagen-rich fibers that form conduits for lymph and support migration throughout the node. This reticular meshwork is denser in medullary cords and peripheral deep cortical units, providing structural integrity without impeding cellular trafficking. Notably, the cortical regions are largely avascular, relying on high endothelial venules (HEVs) for entry; these postcapillary venules, identifiable by their plump cuboidal under H&E, express adhesion molecules that facilitate selective immune cell homing, distinguishing lymph nodes from vascular-rich tissues like .

Vascular and lymphatic flow

Lymphatic flow into the lymph node begins with multiple afferent lymphatic vessels that enter the convex surface of the node, delivering from surrounding tissues directly into the subcapsular sinus located just beneath the capsule. From there, the percolates slowly through a network of sinuses that traverse the cortex and paracortex, allowing for filtration by resident macrophages and exposure to lymphocytes within the lymphoid tissue. This pathway continues into the medullary sinuses, where further processing occurs before the filtered converges and exits via one or more efferent lymphatic vessels at the hilum, the indented region on the concave side of the node. The blood supply to the lymph node is provided by arteries that enter exclusively at the hilum, branching into smaller arterioles that distribute throughout the node. These arterioles give rise to capillaries primarily within the paracortex, where they form a dense network to nourish the high concentration of . The capillaries drain into postcapillary venules, many of which specialize as high endothelial venules (HEVs) characterized by their cuboidal , which facilitates selective entry from the bloodstream. Venous drainage ultimately converges into a single exiting at the hilum, maintaining separation from the lymphatic compartments. Lymph flow dynamics within the node are characterized by a slow, unidirectional progression facilitated by one-way valves in the afferent and efferent vessels, which prevent and promote efficient trapping during the extended in the sinuses. This deliberate process, estimated to handle approximately 4 liters of per day post-nodal , ensures mechanical sieving and immune interaction without rapid transit. While and pathways are anatomically distinct with no direct fluid exchange, limited integration occurs through macrophages that can phagocytose antigens from lymph and present them to blood-derived lymphocytes. Node locations along major lymphatic trunks influence regional flow patterns, directing lymph from specific drainage areas into chains of nodes for sequential filtration.

Function

Lymph filtration and circulation

Lymph nodes serve as primary filters for , processing fluid that drains from tissues through afferent lymphatic vessels into the subcapsular sinus. Here, subcapsular sinus macrophages (SSMs) mechanically trap particulate debris, antigens, and pathogens, such as viruses and , preventing their deeper penetration into the node. This trapping occurs via the macrophages' extended cellular processes that line the sinus floor, capturing particles like 200-nm beads and immune complexes without immediate degradation, thereby acting as a physical . In the medullary sinuses, medullary sinus macrophages (MSMs) further enhance through high phagocytic activity, internalizing and clearing larger volumes of lymph-borne particulates and dying cells using large lysosomes. The filtration process contributes to fluid homeostasis by returning excess interstitial fluid to the bloodstream, maintaining overall balance. Lymph collected from tissues—primarily water, electrolytes, and proteins—is filtered through the node's sinuses and exits via efferent lymphatics, ultimately draining into the , which empties into the left . In a typical adult, this system processes and returns up to 2-4 liters of per day, accounting for the portion of plasma filtrate not reabsorbed by capillaries. As an initial nonspecific barrier, lymph node filtration clears pathogens from incoming before they can disseminate systemically, providing a crucial first line of defense. SSMs and MSMs phagocytose , viruses, and other microbes, reducing their load in the and limiting spread without relying on adaptive immune specificity. This mechanical and phagocytic clearance in the sinuses establishes an early checkpoint, complementing downstream immune processes within the node.

Immune surveillance

Lymph nodes serve as critical checkpoints for immune surveillance, enabling the continuous monitoring of the body's tissues for pathogens and abnormal cells through the orchestrated trafficking of immune cells. Naive T and B lymphocytes constantly recirculate between the blood and lymphoid organs, entering lymph nodes primarily via high endothelial venules (HEVs) in a process mediated by adhesion molecules such as L-selectin and chemokine receptors including CCR7 binding to CCL21, as well as CXCR5 to CXCL13 for B cells. Once inside, these lymphocytes scan antigen-presenting cells within the paracortex and follicles before exiting through efferent lymphatic vessels, a step regulated by sphingosine-1-phosphate (S1P) gradients acting on the S1P1 receptor to promote egress. This recirculation ensures broad patrolling, with naive T cells predominantly traversing T cell zones and naive B cells favoring B cell areas, involving key cell types like lymphocytes and dendritic cells as detailed in the cellular composition section. Complementing lymphocyte recirculation, lymph nodes distinguish between resident and transient populations to enhance surveillance efficiency. Resident cells, such as lymphatic endothelial cells lining the node's sinuses, provide and baseline , while transient dendritic cells migrate from peripheral tissues into the node via afferent lymphatics, guided by CCR7-CCL21 interactions. These migratory dendritic cells transport tissue-derived antigens to the node's interior, bridging peripheral challenges with central immune evaluation without initiating full responses. To prevent during this patrolling, lymph nodes incorporate tolerance mechanisms, particularly in the medulla where peripheral negative selection occurs. Lymphatic endothelial cells in the medullary sinuses express peripheral tissue antigens and directly present self-antigens to delete autoreactive + T cells that escaped thymic selection, independent of the Aire. These cells also express to induce tolerance. This deletional tolerance maintains self-nonself discrimination amid constant cell influx. Under baseline conditions, immune surveillance in lymph nodes involves substantial cellular turnover, with approximately 10^10 to 2.5 × 10^10 recirculating daily in humans. Afferent carries a mix of , macrophages, and dendritic cells, while efferent is lymphocyte-dominant, reflecting the node's role in selective retention and release for ongoing vigilance.

Antigen presentation and response

Antigens entering the lymph node via afferent lymphatics are captured by migratory (DCs) that have taken up pathogens or in peripheral tissues. These DCs enter the subcapsular sinus and crawl along its floor before migrating into the paracortex, the T-cell zone, where they present to naïve T cells. Resident DCs in the lymph node sinuses also contribute to uptake directly from , facilitating rapid transport to the T-cell area via conduits or direct migration. In the paracortex, DCs process antigens for presentation on (MHC) and II molecules. MHC molecules load exogenous antigens derived from endosomal pathways, priming CD4+ T cells, while MHC molecules present endogenous or cross-presented antigens to CD8+ T cells, enabling cytotoxic responses. This T-cell priming involves stable interactions between DCs and naïve T cells, leading to T-cell proliferation, differentiation into effector subsets, and production such as IL-2 and IFN-γ. Activated T cells, particularly follicular helper T (Tfh) cells, then migrate to the T-B border to interact with B cells. B-cell activation occurs in the cortical follicles, where naïve B cells encounter antigens displayed on or directly from subcapsular macrophages. Tfh cells provide co-stimulatory signals via CD40L and cytokines like IL-21, promoting B-cell proliferation and differentiation. This initiates formation within follicles, where B cells undergo in the dark zone and affinity-based selection in the light zone, iterating between zones to refine affinity over several days. High-affinity B cells are selected through competition for and Tfh help, driving class-switch recombination and differentiation. Effector outputs from these responses include cytokine release by activated T cells to amplify and recruit additional immune cells, as well as the generation of T and B cells for long-term immunity. Plasma cells migrate to the medullary cords to secrete high-affinity antibodies, while cells persist in the node or recirculate. This process builds on ongoing immune surveillance to mount targeted adaptive responses.

Pathology and clinical significance

Lymphadenopathy and swelling

Lymphadenopathy refers to the abnormal enlargement of lymph nodes, often resulting from an underlying or pathological process. It is classified into several types, including reactive lymphadenopathy due to infectious or inflammatory stimuli, malignant causes such as or , and autoimmune conditions like systemic lupus erythematosus or . Reactive lymphadenopathy is the most common form and typically benign, resolving once the inciting factor is addressed. Common causes of lymphadenopathy include bacterial and viral infections, which trigger lymph node swelling as part of the . For instance, viral infections like caused by Epstein-Barr virus often lead to , while bacterial infections such as or can cause localized enlargement. Vaccinations, such as those for or , can also induce transient reactive lymphadenopathy due to immune activation. Inflammatory conditions, including autoimmune diseases, further contribute by promoting chronic immune stimulation in the nodes. Clinically, lymphadenopathy presents with distinct features that aid in initial assessment. Tender, painful nodes are characteristic of acute inflammatory or infectious processes, reflecting active immune activity. In contrast, nontender nodes may indicate a more chronic or less inflammatory . The distribution further differentiates cases: localized lymphadenopathy involves contiguous lymph node groups draining a specific site, such as cervical nodes in head and neck infections, whereas generalized involvement affects two or more non-contiguous regions and suggests . Diagnostic evaluation of lymphadenopathy relies on key clinical clues to determine the need for further investigation. Nodes larger than 1 cm in diameter are generally considered enlarged in adults, though normal sizes can vary by location (e.g., up to 1.5 cm in inguinal nodes). Persistence beyond 2 weeks, particularly if accompanied by other symptoms like fever or , raises concern for underlying and prompts additional workup. For comparison, normal lymph nodes are typically smaller than 1 cm and non-palpable in healthy individuals.

Role in cancer

Lymph nodes serve as critical sites for the initial spread of cancer through lymphatic metastasis, where tumor cells from the primary site invade lymphatic vessels and migrate to regional tumor-draining lymph nodes (TDLNs). This process begins with cancer cells detaching from the primary tumor, entering the lymphatics via intravasation, and establishing micrometastases within the node, often before further dissemination to distant sites. Lymph node involvement is a key prognostic indicator, as it facilitates immune evasion and prepares cancer cells for hematogenous spread. In cancer staging, the N category of the TNM system assesses lymph node involvement to determine disease extent and guide treatment. N0 indicates no regional lymph node , while N1, N2, and N3 denote increasing numbers or locations of affected nodes, such as 1-3 nodes for N1 in or involvement of contralateral/supraclavicular nodes for higher stages. This staging is essential for , as nodal correlates with reduced survival rates and influences decisions on adjuvant therapies. Sentinel lymph node biopsy (SLNB) is a targeted procedure to identify and examine the first lymph node(s) draining the , providing prognostic information without extensive node removal. A negative SLNB suggests low risk of further nodal spread, while positivity indicates potential micrometastases and may prompt additional intervention, improving disease-free survival outcomes. SLNB has become standard for early-stage cancers due to its accuracy in detecting metastases. Lymph node is particularly common in , where axillary nodes are frequently the first site of spread, affecting up to 40% of cases at . In , regional nodes along lymphatic drainage paths are primary targets, influencing survival based on burden. often involves mesenteric nodes, with nodal status determining adjuvant needs.

Lymphedema and lymphatic disorders

is a characterized by the accumulation of protein-rich lymphatic fluid in the interstitial tissues, leading to swelling primarily in the arms or legs due to impaired lymphatic drainage. This disorder arises from dysfunction in the , including lymph nodes, resulting in an imbalance of Starling's forces that normally regulate fluid exchange between capillaries and tissues, causing excessive fluid retention. Causes of lymphedema are classified as primary or secondary. Primary lymphedema is congenital, stemming from genetic malformations of the lymphatic vessels and nodes present at birth, such as , which affects approximately 1 in 100,000 individuals in the United States. Secondary lymphedema results from acquired damage to the lymphatic system, including surgical removal of lymph nodes, as seen post-mastectomy for , parasitic infections like caused by Wuchereria bancrofti, or other injuries such as . The condition progresses through stages marked by increasing severity of and tissue changes. In early stage 1, swelling is pitting and reversible with elevation, reflecting initial fluid accumulation without significant . Stage 2 involves non-pitting due to developing , while stage 3 features severe, irreversible swelling with skin thickening and fat deposition, often termed . This progression is driven by chronic and disruption of Starling's equilibrium, where elevated interstitial from protein buildup exacerbates fluid leakage from capillaries. Beyond , other lymphatic disorders include and lymphatic malformations. is an acute inflammation of lymphatic vessels, typically caused by bacterial spreading from a , presenting with red streaks, fever, and tender lymph nodes. Lymphatic malformations are congenital anomalies involving malformed lymphatic channels that form fluid-filled cysts, often appearing at birth and potentially leading to localized swelling or complications like . Treatment for lymphedema and related disorders emphasizes non-surgical conservative measures to manage symptoms and prevent progression. Compression therapy, using bandages or custom-fitted garments, applies graduated pressure to promote lymphatic flow and reduce swelling. involves gentle, specialized massage techniques to stimulate fluid movement toward functional vessels, often combined with exercise to enhance muscle pump action. These approaches, part of complete decongestive therapy, focus on symptom control rather than cure.

Diagnostic procedures

Diagnostic procedures for lymph nodes are employed when enlargement or abnormalities are suspected, often prompted by clinical signs such as swelling. These methods range from non-invasive assessments to invasive sampling, allowing evaluation of node structure, cellular composition, and potential . serves as the initial clinical examination for superficial lymph nodes, involving gentle pressure to assess size, shape, consistency, mobility, and tenderness. Nodes larger than 1 cm in diameter, firm, fixed, or matted are considered abnormal and warrant further investigation. This technique is particularly useful for accessible regions like the cervical, axillary, and inguinal areas but is limited for deep nodes. Imaging techniques provide detailed visualization without initial tissue sampling. is often the first-line modality for superficial nodes, evaluating size, shape, echogenicity, margins, and vascular pattern via Doppler; for instance, a short-to-long axis ratio less than 2 suggests malignancy with high accuracy. Computed tomography (CT) and are preferred for deep or internal nodes, assessing size, morphology, and involvement of surrounding structures, though they rely primarily on anatomical changes. Positron emission tomography (PET), typically combined with CT, measures metabolic activity using tracers like FDG, offering superior sensitivity and specificity for detecting active disease processes compared to structural imaging alone. Invasive procedures are pursued when imaging or palpation indicates concern, to obtain material for definitive analysis. Fine-needle aspiration (FNA) involves inserting a thin needle, often ultrasound-guided, to extract cells and fluid for cytological examination; it has a sensitivity of 85-97% and specificity of 98-100%, making it suitable for initial in accessible nodes. Core needle biopsy uses a larger, cutting needle to retrieve a tissue core, providing histological detail and higher diagnostic yield than FNA, especially when guided by for precision. Excisional biopsy surgically removes the entire node under anesthesia, serving as the gold standard for comprehensive evaluation, particularly when architecture preservation is needed for accurate diagnosis. Following invasive sampling, examines the retrieved material under to identify cellular abnormalities, infections, or malignancies. This includes hematoxylin-eosin for general morphology, supplemented by or for specific markers, enabling differentiation of reactive, infectious, or neoplastic processes with near-complete accuracy when adequate tissue is available.

Comparison to spleen

Lymph nodes and the are both secondary lymphoid organs that play critical roles in immunity, but they differ markedly in structure to accommodate their distinct filtration environments. Lymph nodes feature a fibrous capsule enclosing a subcapsular sinus that receives from afferent vessels, an outer cortex divided into B-cell follicles and a T-cell paracortex, and an inner medulla with cords of lymphoid cells and macrophages alongside medullary sinuses for drainage. In contrast, the consists of red pulp, which comprises the majority of its volume and includes venous sinusoids for , and white pulp, organized into periarteriolar lymphoid sheaths (T-cell zones) and B-cell follicles surrounding central arteries, with a marginal zone bridging the two pulps for capture. Unlike lymph nodes, the lacks afferent lymphatic vessels and a subcapsular sinus, as all incoming material arrives via rather than , and it is enveloped by a thin capsule without trabeculae extending deeply into the red pulp. Both organs contain similar lymphoid cell populations, including T and B lymphocytes, but the 's supports closer interaction with circulating elements. Functionally, lymph nodes primarily filter lymph fluid draining from tissues, trapping pathogens and antigens for presentation to immune cells, thereby facilitating adaptive responses to tissue-derived threats. The spleen, however, filters blood directly, with its red pulp macrophages removing aged or damaged red blood cells, recycling iron, and clearing blood-borne particles like or parasites, in addition to mounting immune responses via the white pulp to systemic antigens. While both organs support immune surveillance through antigen-presenting cells and lymphocyte activation, the spleen emphasizes hematologic maintenance—such as preventing accumulation of defective erythrocytes—roles absent in lymph nodes. In terms of location, lymph nodes are distributed throughout the body in clusters along lymphatic vessels, numbering approximately 800 in adults and concentrated in regions like the , axillae, , and to monitor specific drainage areas. The , by comparison, is a singular, encapsulated organ situated in the upper left quadrant of the , posterior to the and superior to the left , making it the largest dedicated lymphatic structure at about 12 cm long. Clinically, removal of the spleen () carries risks such as (OPSI), a fulminant from encapsulated bacteria like , with a lifetime incidence of 1-3% and mortality rate of 38-70%. Lymph node excision, often performed in or treatment, primarily risks due to disrupted lymphatic drainage, with odds increasing fivefold for 6-15 nodes removed and tenfold for 16 or more, particularly in axillary or inguinal dissections.

Comparison to tonsils and Peyer's patches

Lymph nodes, tonsils, and Peyer's patches are all secondary lymphoid organs that facilitate the initiation of adaptive immune responses by enabling encounter with lymphocytes, but they differ significantly in their structural organization and integration with the . Unlike lymph nodes, which are encapsulated structures with both afferent and efferent lymphatic vessels allowing lymph to flow through for filtration and transport, tonsils and Peyer's patches lack efferent lymphatics and are directly embedded within mucosal epithelia. This embedding in tonsils (oropharyngeal mucosa) and Peyer's patches (intestinal mucosa) positions them as specialized components of (MALT), where they rely on local drainage rather than a complete vascular lymphatic circuit. Functionally, while all three structures support antigen presentation and lymphocyte activation, tonsils and Peyer's patches are adapted for direct sampling of luminal antigens from mucosal surfaces, primarily through microfold (M) cells in the overlying follicle-associated epithelium, which transport antigens to underlying dendritic cells and lymphocytes for mucosal immunity, including IgA production. In contrast, lymph nodes primarily process antigens delivered via afferent lymph from peripheral tissues, serving as centralized hubs for systemic immune surveillance and responses that can disseminate effectors body-wide. Both tonsils and Peyer's patches promote tolerance to commensal microbes alongside immunity, with T-cell-dependent IgA class switching in Peyer's patches being a key feature, whereas lymph nodes emphasize broader T- and B-cell priming for circulating immunity. Locationally, lymph nodes are distributed systemically along lymphatic vessels at junctions with blood vasculature, enabling them to intercept antigens from diverse tissues, whereas tonsils are fixed in the oropharynx as part of Waldeyer's ring, and Peyer's patches form discrete aggregates in the small intestine's , optimizing exposure to inhaled or ingested antigens. Evolutionarily, MALT structures like tonsils and Peyer's patches represent ancient mucosal adaptations, with organized emerging in sarcopterygian fish as primitive lymphoid aggregates, while lymph nodes evolved as more centralized, encapsulated organs in higher vertebrates to coordinate systemic responses, integrating MALT-derived signals.

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