The Lymphatic System: Vessels and Tissues

• The lymphatic system includes lymphatic vessels and lymphatic tissues.

Lymphatic Vessels

• Lymphatic vessels (LVS) begin in tissues as blind-ended lymphatic capillaries.
• These capillaries give rise to lymphatic vessels, which then form lymphatic ducts.

Lymphatic Tissues

• Lymphatic tissues include:
• Lymph nodes
• Spleen
• Scattered lymphatic nodules in certain organs
• Tonsils
• Thymus

Afferent vs. Efferent Lymph Vessels

• Afferent lymph vessels carry lymph to lymph nodes.
• Afferent lymph enters the lymph nodes via the convex surface.
• Lymph in afferent vessels contains fewer antibodies & lymphocytes.
• Efferent lymph vessels carry lymph away from lymph nodes.
• Lymph in efferent vessels contains more antibodies & lymphocytes.
• Efferent lymph exits the lymph nodes through the hilum (concave surface).

Blood vs. Lymph Capillaries

• Blood capillaries are superficial, located under the skin and mucous membranes.
• Blood capillaries branch from arterioles, connecting to venules.
• Blood capillaries have a small, uniform diameter, basement membranes and pericytes, potent and less permeable lumen and carry blood..
• Lymph capillaries are located deeper than blood capillaries.
• Lymph capillaries start as blind-ended channels, connecting to lymph vessels, larger & irregular diameter, no basement membrane or pericytes, lumen may be collapsed but is more permeable and carry lymph.

Lymphatic Organs

• Lymphatic organs are classified into primary and peripheral (secondary) categories.

Primary Lymphoid Organs (Central)

• Primary Lymphoid Organs are where lymphocytes are produced, developed, and matured into immunocompetent cells.
• Primary Lymphoid Organs include the pre- and postnatal bone marrow and the thymus.

Secondary Lymphoid Organs (Peripheral)

• Secondary Lymphoid Organs are sites where lymphocytes respond to antigens.
• Secondary Lymphoid Organs include:
• Lymph nodes
• Tonsils
• Spleen
• Mucosa-associated lymphoid tissue

Thymus Definition

• The thymus is a primary lymphatic organ.

Thymus Function

• The thymus is the site of T-lymphocyte maturation.

Thymus Location

• The thymus is located in the superior mediastinum thoracic cavity behind the sternum, extending upwards into the neck.

Thymus Size

• Thymus size varies greatly with age.

Thymus Structure

• The thymus is a single structure composed of two lobes.

Thymus Stroma

• The stroma consists of a capsule.
• It is formed of a thin C.T capsule made of dense, irregular collagenous C.T.
• Septa (trabeculae) extend from the capsule, dividing the lobe into incompletely separated lobules (thymic lobules).
• Reticular fibers form a fine reticular net structure.

Thymus Parenchyma

• Thymic lobules contain an outer darkly stained cortex and an inner pale medulla.
• The medulla may be continuous between lobules.
• The Cortex contains:
• Many lymphocytes
• Epithelial reticular cells that are branched and linked by desmosomes
• Lymphoblasts, located in the outer parts of the cortex
• Macrophages, which are large phagocytic cells

Medulla of Thymic Lobules

• The medulla contains T-lymphocytes, lymphoblasts, macrophages, and a larger number of epithelial reticular cells.
• Hassall's corpuscles (thymic corpuscles) are characteristic large, rounded structures in the medulla.
• They consist of concentrically arranged flattened epithelial reticular cells.
• The central part is homogenous and acidophilic, exhibiting degeneration, hyalinization, and calcification.
• Each corpuscle resembles an onion in cross-section.

Epithelial Reticular Cells Functions

• Epithelial reticular cells secrete thymic growth factors (thymic hormones) like thymosin, thymopoietin, thymulin, and thymic humoral factors.
• These factors function in a paracrine manner, facilitating T-cell proliferation and surface marker expression.
• Epithelial reticular cells are antigen-presenting cells (APCs) that express epitopes MHC molecules on their surface.

Blood-Thymic Barrier

• The blood-thymic barrier isolates the thymus's cells, protecting developing T-cells in the cortex from blood-borne macromolecules.
• The blood-thymic barrier is only present in the cortical zone.
• The layers include:
• Endothelial cells of blood capillaries
• Basement membrane of blood capillaries
• Macrophage cells outside the capillaries, which remove antigens.
• Epithelial reticular cells forming a sheath around capillaries and macrophages.

Functions of Thymic Barrier

• The thymic barrier protects thymic T-lymphocytes from circulating blood.
• The thymic barrier prevents newly formed T-lymphocytes from exposure to circulating antigens.

Function of Thymus

• The thymus facilitates the normal development (proliferation and differentiation) of lymphoid tissue and maturation of immunological responses.

Thymic Dependent Zone

• The thymic dependent zone is an area in secondary lymphoid tissue that contains mainly T-lymphocytes.
• It is present in:
• The paracortical zone of lymph nodes
• The periarterial lymphatic sheath in white pulp of the spleen
• Diffuse lymphoid tissue in Peyer's patches

Lymph Nodes Definition

• Lymph nodes are small, encapsulated, oval or rounded organs.
• Lymph nodes are secondary (peripheral) lymphatic organs.
• Lymph nodes are situated in the passage of lymph vessels.
• Lymph nodes function to filter lymph for bacteria and other foreign bodies.

Lymph Node shape

• Lymph nodes have a convex surface perforated by afferent lymph vessels.
• The concave surface (hilum) is where arteries enter and veins & efferent lymph vessels exit.
• Afferent & efferent lymphatics have valves to prevent backflow.

Lymph Node Structure

• Lymph nodes consist of a stroma and parenchyma.

Lymph Node Stroma

• The stroma is the framework of the lymph node.
• The capsule that surrounds the lymph node is a dense fibrous irregular collagenous C.T., thickening toward the hilum.
• Trabeculae are dense fibrous C.T. septa from the capsule that extend into the node, dividing the outer region into incomplete cortical compartments to the vicinity of the hilum, branching and anastomosing in medulla.
• Reticular C.T. creates a network to support immunocompetent cells within the node.

Lymph Node Parenchyma

• Histologically, lymph nodes have a cortex, paracortex, and medulla.
• Cortex:
• Forms the outer zone of the lymph node.
• Is divided into incomplete compartments housing lymphoid nodules and cortical sinuses.
• Lymphoid nodules classify as primary or secondary.
• Primary Lymphatic Nodules:
• Rounded or oval in shape.
• Lack a pale center (germinal center).
• Contain an aggregation of small B-lymphocytes.
• Secondary Lymphatic Nodules:
• Consist of a central pale area called the germinal center and a peripheral dark zone.
• The peripheral zone is dark due to intense staining of the nuclei of closely packed small lymphocytes.
• The germinal center stains pale because most cells are large, with abundant and pale cytoplasm, and contains large B-lymphocytes.

Function of Nodules

• Nodules produce lymphocytes and antibodies.
• Nodules have phagocytic activity due to the presence of macrophages, the macrophage system filters the lymph (as in the lymph nodes) and the blood(as in spleen).
• The region peripheral to the germinal center in a secondary nodule is the mantle. The mantle is where activated lymphocytes aggregate in the lymphatic nodule center.
• The activated pale germinal center contains:
• Activated B-lymphocytes
• Macrophage cells
• Dendritic reticular cells
• The germinal center displays three zones: a dark zone, a basal light zone, and an apical light zone.

Cortical Lymphatic Sinuses

• Cortical lymphatic sinuses are irregular lymph spaces, lined with endothelial cells, that receive lymph from afferent lymph vessels.
• Cortical lymphatic Sinuses are divided in the following types:
• Subcapsular sinuses
• Trabecular sinuses
• Paracortical sinuses, located at the cortico-medullary junction
• Cortical Lymphatic Sinuses contain diffuse lymphocytes, macrophages and plasma cells held by reticular net fixed to it reticular cells

Thymus-Dependent Zone (Paracortex)

• The thymus-dependent zone, or paracortex, is morphologically ill-defined, but functionally distinct, the paracortex between cortex and medulla contains post-capillary venules, T-lymphocytes, and macrophages, and it is why is also called thymus-dependant zone. T-cells migrate through medullary sinus before antigen activity.

Medulla

• The medulla is composed of medullary cords and sinuses.
• Medullary lymphatic cords:
• Aggregations of lymphocytes in organized structures.
• Branch and anastomose, containing T-lymphocytes, plasma cells, and macrophages.
• Supported by reticular net.
• Medullary lymphatic sinuses:
  • Irregular wide spaces between medullary cords.
  • Lined with non-continuous basement membranes and flat endothelial cells.
  • Contain free lymphocytes, macrophages, and plasma cells.

Pig Lymph Nodes

• Pig lymph nodes differ from those of other mammals:
• Lymphatic nodules are present centrally.
• Most nodules occupy a deep position along the trabecular sinuses.
• Lymphatic cords are peripherally located.
• Sinuses are narrow, medullary cords are absent.
• The node's periphery contains primarily loose lymphoreticular tissues with macrophages and few plasma cells.
• Afferent lymphatic vessels are located near the lymphatic cords and join the trabecular sinuses after penetrating the trabeculae.
• Lymph filters from the trabecular sinuses into peripheral sinuses and converge to form efferent lymph vessels at the periphery.
• A definitive hilus may be absent.

Lymph Node Function

• Lymph node Functions include filtration and phagocytosis.
• The cortex consists of antigen processing of antigenic material by cortical macrophages and lymphocytes.
• Lymphopoiesis and Immunologic responses occurs in lymph.
• Matter is filterer out and engulfed by macrophages of medullary sinuses.

Spleen Definition

• The spleen is the largest lymphatic organ in the body and filters blood.
• Unlike lymph nodes, it only contains efferent lymphatic vessels, not afferent vessels.

Spleen Structure

• Is composed of stroma and parenchyma.

Spleen Stroma (Framework)

1. Capsule:

• The spleen is surrounded by a dense C.T capsule covered with peritoneum.
• It consists of smooth muscle fibers and is outside covered by serous membrane.
• Thicken forming the hilum allowing the passages of vessels and nerves.
• It is thin in human, thick in animals.

2. Trabeculae:

• Long thick and irregular septa radiating around and from the hilum.
• Trabeculae contain branches of the splenic artery and vein and they don't divide the spleen into compartments.

3. Reticular C.T

• Is the network of reticular C.T fibers and cells that support the parenchyma and form the background for the white and red pulps of the spleen.

Spleen Parenchyma

• B) Parenchyma: Soft tissue and constitutes the C.T framework of spleen.
• In the fresh state, there are 2 types of pulps:.
• White pulp (lymphatic nodules of spleen)
• Red pulp.

White pulp (Mapighian corpuscles)

• Consists of rounded elongated lymphatic nodules.
• Appears white or grayish in fresh spleen sections due to lymphocyte condensation around the arteries.
• The nodules feature reticular C.T with small lymphocytes.

4 Zones of White Pulp

• Thymus-Dependent Zone (PALS): Periarterial Lymphatic Sheath - surrounds the central artery, formed mainly of T- lymphocytes.
• The Germinal Center Zone: Surrounds the thymus-dependant zone, in the center of lymphatic nodule, formed mainly of B-lymphocytes and large activated lymphocytes.
• The follicular zone: Surrounds the germinal zone, formed mainly of B-lymphocytes.
• The marginal zone: Forms the periphery of white pulp formed of diffuse tissue located between the lymphatic nodule and the red pulp. - Consists of T and B lymphocytes, denderitic reticular, plasma cells, macrophages for immunological response.

Red pulp

• It has a loose consistency: contains splenic cords and sinuses giving it this loose consistency and appears red due to presence of RBCs.
• Splenic cords (Billroth cords): Network of reticular fibers and reticular cells consisting of lymphocytes, plasma cells, macrophages, monocytes, erythrocytes (RBCs) and granular leukocytes (WBCs) and is rich in phagocytic cells such as histiocytes, macrophages and monocytes.

Splenic sinuses

• Consists out of wide irregular blood spaces, lined by elongated fusiform endothelial and macrophage cells (Littoral cells).

Spleen Functions

1- Filtration of the blood:

• The marginal zone is rich in macrophages which phagocytose blood-born antigens, bacteria and foreign particular matter.

2- Forming lymphocytes:

• Formed in the white pulp in response to antigen

3- Elimination or inactivation of blood-born antigens:

• Soluble antigens are inactivated by antibodies, phagocytosed by macrophages or neutrophils.

4- Destruction of aged erythrocytes:

• Old erythrocyte are in some cases destroyed surface coats but are phagocytosed/hemoglobin destroyed in phagosome.
• Iron is carried back to bone marrow
• Heme hemoglobin bilirubin + excreted in bile
• Globin disassembled into amino acids

5- Participation in hemopoiesis:

• Happens in the 2nd trimester of gestation and postnatally if necessary.

6- Storage of blood: Contracts during bleeding events.

Mucosa Associated Lymphoid Nodules (Definition)

• Non-capsulated, localized lymphocytes and lymphoid nodules in the mucosa of the gastrointestinal and respiratory tracts.
• They are scattered in the epithelium of the small and large intestines, and they are present in large numbers in the epithelium overlying the Peyer’s patches.
• These lymphocytes are almost exclusively T-cells.

Diffuse Lymphocytes

• Scattered within the lamina propria of respiratory, digestive, and urinary systems.

• Include:

• Gut-Associated Lymphoid Tissue (GALT): Composed of lymphoid follicles along the length of GIT (In the ileum: Peyer’s patches), composed of B-cells surrounded by a looser region of T-cells lined by M-cells (microfold cells)

• The regions of epithelium immediately adjacent to the lymphoid follicles are lined by cells known as M-cells (microfold cells).

  • These cells capture antigens and transfer them without processing the macrophages.

• Bronchus-Associated Lymphoid Tissue (BALT): Located in the walls of the bronchi, especially at the bifurcations of the bronchi and bronchioles.

Lymphatic Nodules are divided:

1- Solitary lymphatic nodules 2- Aggregated lymphatic nodules

Tonsils

• Tonsils are incompletely aggregates of lymphoid tissues that guard the entrance to the oral pharynx (oro- and nasopharyngeal junctions), acting on airborne/ingested antigens forming lymphocytes. They are located within the lamina propria.
• The parenchyma consists of several lymphoid nodules, several of which have germinal centers which indicates B-cell formation.
• Tonsilar glands (mucosal glands) are mixed in carnivores, they open into the tonsilar crypts or sinuses.
• Covered surface epithelium covering the lymph nodules go through by irregularity (invagination (forming crypts) or bulging (forming sinuses).

Tonsils with crypts

• Where the epithelium is invaginated to form tonsilar crypts, surrounded by lymphatic nodules.
• Diffuse lymphoreticular tissue is called tonsilar follicle ex palatine tonsil (man, horses, ruminants and swines).
• In ruminants, the presence of branched tonsilar crypts which communicate with the surface are known tonsilar sinus.

Tonsils without crypts

• Surface epithelium bulges outwards forming a tonsilar sinus
• Several lymphatic are underneath epithelium
• Diffuse lymphoreticular is located between this point. e.g. palatine tonsils (carnivores) or all tonsils in domesticated animals unless carnivores.

Lymph Node vs Spleen

• Lymph nodes are small, but multiple bodies present in groups, but the spleen is a single organ.
• Lymph nodes filter the lymph but the spleen filters blood.
• Lymph Nodes is covered in fascia, like in elastic fibers which thick and can be adherent, but splenic is covered in pertoneum
• Lymph nodes have Afferent and Efferent but Spleen has only Efferent.
• Compared to Spleen Nodes have small trabuculae from the small capsule but there is long trabucuel arise from the hilum.