LYMPHATIC SYSTEM

As blood circulates through the body, exchanges of nutrients, wastes and gases occur between the capillaries and tissue spaces. These leaked interstitial fluids from capillaries must be carried back to the blood if the vascular system is to have sufficient blood volume to operate. The lymphatic vessels pick up this excess fluid, now called lymph and return it to the bloodstream. As lymph is transported toward the heart, it is filtered through lymph nodes that cluster around lymph vessels. In the lymph nodes are macrophages which engulf and destroy pathogens in the lymph before it returns to the blood.

The lymphatic system consists of lymphatic fluid, lymphatic vessels, lymphatic tissue, and lymphatic organs located throughout the tissues of the body. It functions to: 1-Drain excess interstitial fluid from the tissues and return to blood stream 2-Initiate an immune response against disease by producing and transporting lymphocytes 3-Transport dietary lipids absorbed by the gastrointestinal tract into the blood.
Lymph is a colorless fluid that floats in the lymphatic vessels. It is similar in composition to blood plasma Lymphatic vessels are thin vessels that accompany arteries and veins throughout the body and transport lymph.
Lymphatic tissue is a specialized form of reticular connective tissue that is composed of masses of lymphocytes. These either occur alone as lymph nodules (follicles) or are organized into various lymphatic organs.
Lymphatic organs include the lymph nodes, spleen, thymus, and red bone marrow The tissues of the body are supplied by blood capillaries that bring oxygen-rich blood and remove carbon dioxide-rich blood.
Around 20 liters of fluid leaves the arterial capillaries every day, but only 17 liters of fluid returns to the venous capillaries.
Fluid similar to blood plasma, called interstitial fluid, leaches from these vessels into the surrounding tissue.
Lymphatic vessels function to drain this excess fluid from the tissues as lymph and return this fluid to the blood.
Lymphatic vessels begin as "porous" blind-ended lymphatic capillaries in tissues of the body and converge to form a number of larger vessels, which ultimately connect with large veins in the root of the neck. (blind-ended) Lymph returns back to the big veins (venous angle: the junction between subclavian and internal jugular veins) through the Thoracic duct and Right lymphatic duct. Dr.

Arterial side
When fluid accumulates in the tissue, interstitial pressure increases pushing the flaps inward, opening the gaps between cells, allowing fluid to flow in. As pressure inside the capillary increases, the endothelial cells are pressed outward, closing the gaps, thus preventing backflow. Unlike blood capillaries, the gaps in lymphatic capillaries are so large that they allow bacteria and immune cells (ex. Macrophages/ dendritic cells) to enter. This makes the lymphatic system a useful way for large particles to reach the bloodstream.

Transport
Some lipids are too large to pass through the capillary walls of the small intestine and therefore cannot be absorbed.
The lymphatic capillaries within the small intestine, known as lacteals, can absorb these large lipid molecules and transport them into the venous circulation via the thoracic duct. Lymph containing these lipids becomes a creamy white color and is referred to as chyle.
Lymphocytes can be found throughout the body, however, they aggregate in places where they are most likely to come into contact with pathogens.
Lymphocytes are produced within the red bone marrow and are transported via the blood vessels to lymphatic tissues and organs.

Self
Non-Self

Lymph nodes
✓ Are kidney-shaped small encapsulated bodies located along the course of lymphatic vessels (Approximately 600 lymph nodes ) ✓Reticular tissue forms the stroma of the lymph node ✓Lymph nodes are up to 3 cm in length ✓Immunocompetent B cells and T cells are suspended throughout the lymph node ✓Nodes filter the lymph, removing foreign material and microorganisms. ✓ All lymph is filtered by at least one lymph node before it returns to the blood. ✓Antibodymediated and cell-mediated immune responses occur in the lymph nodes ✓Lymph nodes congregate around blood vessels in clusters and are usually named according to the vessel or location that they are associated with. Dr.

Kalbouneh
Lymph node enlargement can happen in cases of lymphoma (painless lymphadenopathy) or infection (painful).
Lymph nodes are production sites of antibodies and activated lymphocytes

Medulla
The nodes are covered by a capsule of dense connective tissue, and have capsular extensions called the trabeculae, which provide support for blood vessels entering into the nodes.
When lymph nodes become enlarged, the capsule is stretched and becomes painful The cortex is the outer, highly cellular part of the lymph node; it can be divided into an outer cortex and inner paracortex. Dr.

Kalbouneh
The outer cortex has lymphatic follicles that mostly contain B-cells.
The inner cortex (paracortex) contains mostly T-cells.
The medullary cords contain mostly plasma cells.
Other cells in the lymph node:

Macrophages Dendritic cells Follicular dendritic cells Reticular cells
Both the macrophages, and the dendritic cells trap antigens and present them on their surfaces As B cells in lymphatic follicle are stimulated, they differentiate into plasma cells. Plasma cells move to medulla (medullary cords)

Cortex and medulla
Outer cortex Are antigen HOLDING cells Holds the Ag for long time

Macrophage Dendritic cell
Macrophages and Dendritic cells capture antigen within tissues and transport antigen to secondary lymphoid tissue Dr.

Kalbouneh
The medulla is the deep, cavitated part of the lymph node; it is composed of medullary cords The cords are separated by spaces known as medullary sinuses The medullary sinuses converge at the hilum.

Medullary cords Medullary sinuses Hilum
The hilum is a slight indentation on one side of the node. Here, an artery, vein, and an efferent lymphatic vessel enter and leave the node.

Afferent vessels
Many afferent lymphatic vessels enter the lymph node at different points over its convex surface, each containing valves to prevent backflow of lymph.

Subcapsular sinuses
Each afferent vessel empties into the subcapsular sinus.

Trabecular sinuses
The trabecular sinuses are a continuation of the subcapsular sinuses that follow the trabeculae and drain into the medullary sinuses.

Medullary sinuses
Found separating the cords. The medullary sinuses converge at the hilum into the efferent lymphatic vessel.

Efferent vessels
The lymph is removed from the medullary sinus via one or two efferent lymphatic vessels that leave the lymph node at the hilum. Valves in the vessels prevent lymph from flowing in the wrong direction.

Sinuses are irregular spaces through which the lymph percolates
Dr.

Lymph flow
Lymph nodes are linked together by lymphatic vessels. Lymph flows through a lymph node via a series of sinuses and lymphatic tissue Lymph, containing micro-organisms, soluble antigens and antigen presenting cells, enters the lymph node via afferent lymphatic vessels (1) which enter the subcapsular sinus (2). It then runs through trabecular (cortical) sinuses (3) then into medullary sinuses (4) and leaves through the efferent lymphatic vessels (5), at the Hilum as efferent lymph.
Efferent lymph contains lots of activated Tlymphocytes, activated B-lymphocytes, plasma cells and antibodies.
All the lymphatic sinuses are lined by a discontinuous layer of simple squamous endothelium This diagram of a lymph node shows the pathways that lymphocytes can take, in and out of the lymph node.
The structure of the post-capillary venule, in the paracortex is unusual in that it is not lined by simple squamous epithelium, but by a simple cuboidal epithelium. These are called high endothelial venules (HEVs) Lymphocytes recognize and adhere to these endothelial cells, and squeeze through them into the paracortex The process of lymphocyte recirculation is regulated by adhesion molecules on lymphocytes called Homing receptors and their ligands on vascular endothelial cells called Adressins Lymphocytes can enter lymphoid tissues in two ways: 1) Direct entry into lymph nodes via afferent lymphatics 2) Entry from blood capillaries across specialized endothelial cells present in the postcapillary venules (High Endothelial Venules= HEV) within the paracortex of the lymph node Why naïve lymphocytes migrate preferentially to lymph node????? Dr.

Heba
Kalbouneh Note: Most of the lymphocytes enter the lymph nodes via blood vessels, and about 10% enter through the lymph.
Heba Kalbouneh Try to describe these histological sections and the clinical picture a patient would have in each case

Lymphatic trunks and ducts
All lymphatic vessels coalesce to form larger trunks which eventually converge to form the right lymphatic duct and the thoracic duct In cases of portal hypertension, spleen often enlarges from venous congestion.

Superior mesenteric vein
Portal vein

Heba Kalbouneh
The parenchyma of the spleen appears in fresh specimen as: White pulp which appears white on gross examination (collection of both B and T lymphocytes) Red pulp which appears red on gross examination (blood filled)

White pulp
Dr.

Kalbouneh
The spleen is composed of parenchyma and stroma Parenchyma: Splenic pulps Stroma: Reticular tissue (reticular fibers and reticular cells)

Capsule
Red pulp

White pulp
Trabeculae Vein There are two types of pulp in the spleen:

Artery Central arteriole
The spleen is covered by a capsule of dense connective tissue, and have capsular extensions called the trabeculae Large trabeculae originate at the hilum, on the medial surface of the spleen, and carry branches of the splenic artery, vein, lymphatics, and nerves into the spleen Dr.

Trabecular arteries
Follow the course of trabeculae

Central arterioles
Are branches of trabecular arteries entering the white pulp. They are surrounded by a sheath of lymphocytes.

Penicillar arterioles
Each central arteriole eventually leaves the white pulp and enters the red pulp, losing its sheath of lymphocytes and branching as several short straight penicillar arterioles that continue as terminal capillaries.
Open circulation: the capillaries open into the spaces of the red pulp (splenic cords) and then the blood returns to the venous system through the wall of the splenic sinusoids Closed circulation: the capillaries open directly into the splenic sinusoids (blood is enclosed by endothelium)

Trabecular veins
Blood flow through the splenic red pulp can take either of two routes:

Splenic sinusoids
The morphology is like penicillus Terminal capillaries (Sheathed capillaries) Some of these terminal capillaries are sheathed with APCs for additional immune surveillance of blood Dr.

Heba Kalbouneh
White pulp (lymphoid tissue) ✓ Constituting 25% of the spleen, the white pulp is responsible for the immunological (lymphatic) function of the spleen. ✓ The white pulp contains: Periarteriolar lymphatic sheaths (PALS): tightly packed T cells arranged in cylindrical sheaths around central arterioles

Splenic nodules (Malpighian corpuscles)
Note: These follicles have the same structural organization as those found in lymph nodes

Function:
The lymphocytes and APCs monitor the blood for foreign antigens and respond in a similar way to those in the lymph nodes. Dr.

Kalbouneh
Production of antibodies and activated lymphocytes (which are delivered directly into the blood) When the lymphatic sheath expands to incorporate the follicles, the central arteriole is displaced to one side and acquires an eccentric position in the follicle but is still called the central arteriole (Follicular arteriole).

Reticular cell
Note: When B cells in the primary follicles are exposed to Antigen, they proliferate and differentiate to plasma cells and move toward the red pulp.
In this route plasma and all the formed elements of blood must reenter the vasculature by passing through narrow slits between the stave cells into the sinusoids. These small openings present no obstacle to platelets, to the motile leukocytes, or to thin flexible erythrocytes. However stiff or swollen RBCs at their normal life span of 120 days are blocked from passing between the stave cells and undergo selective removal by macrophages Deformed or less pliable RBCs cannot squeeze effectively from the cord into the sinus and upon their mechanical fragmentation are removed by resident macrophages (lie just next to the sinusoids) Macrophages monitor erythrocytes as they migrate from splenic cords between the endothelial cells into the splenic sinusoids Old erythrocytes lose their flexibility They cannot penetrate the spaces between the endothelial cells and are phagocytosed by macrophages Old erythrocytes lose sialic acid from their cell membranes Galactose exposed

Induce phagocytosis of RBCs
Hemoglobin is broken into Heme and Globin Iron: carried by transferrin to bone marrow (used again) Bilirubin: excreted by liver bile amino acids pool of blood Dr.
Heba Kalbouneh Schematic view of the blood circulation and the structure of the spleen, from the trabecular artery to the trabecular vein.
The following events occur at the marginal zone: 1-APCs sample the material travelling in blood searching for antigens 2-Macrophages attack microorganisms present in the blood 3-The circulating B and T cells leave the blood stream to enter the preferred location within the white pulp

T cells: PALS B cells: lymphatic follicles
Lymphocytes come into contact with APCs, if they recognize their Ag-MHC complex, the lymphocytes initiate immune response within the white pulp Marginal zone sinuses ✓ Located between the white and the red pulp ✓The spaces between these sinuses are wide (2-3um) It is here the blood-borne antigens and particulate matter have their first free access to the parenchyma of the spleen Dr.

Functions of the spleen:
It has circulatory as well as lymphatic functions Blood cell production: During the fetal life, blood cells are produced in the spleen Blood storage: A small quantity of blood is stored in the sinusoids of the red pulp RBC destruction: Most worn-out or damaged red blood cells are destroyed in the spleen (some in the liver and bone marrow). They are phagocytized by macrophages Defense mechanism: Macrophages phagocytize microbes that have penetrated the blood. Antigens in the blood activate B and T cells residing in the spleen, triggering immune response

MALT is populated by: T cells B cells Plasma cells APCs
Each of which is well situated to encounter antigens passing through the mucosal epithelium

Diffuse lymphatic tissue (lymphatic nodules)
Lymphatic nodules Because lymphocytes have prominent basophilic nuclei and very little cytoplasm, lymphoid tissue packed with such cells usually stains dark blue in H&E stained sections Dr.

Kalbouneh
The mucosa or inner lining of the digestive, respiratory, and genitourinary tracts is a common site of invasion by pathogens because their lumens open to the external environment.
Collectively the MALT is one of the largest lymphoid organs, containing up to 70% of all the body's immune cells.

Palatine tonsils
Are located at the lateral wall of oropharynx, between the glossopalatine and pharyngopalatine arches (two masses ) Acute inflammation of these tonsils causes tonsillitis.

Pharyngeal tonsils
Are located in the posterior wall of the nasopharynx.
It is most prominent in children, but begins to atrophy from the age of seven. Hypertrophied regions of pharyngeal tonsils resulting from chronic inflammation are called adenoids.

Nasal septum
Lingual tonsils Are located on the posterior 1/3 of the tongue. Function of tonsils: Protect the body from inhaled and ingested pathogens.

Dr. Heba Kalbouneh
Tonsils are large, irregular masses of lymphoid tissue Adenoids Excessive hypertrophy of the lymphoid tissue, usually associated with infection, causes the pharyngeal tonsils to become enlarged; they are then commonly referred to as adenoids. Marked hypertrophy blocks the posterior nasal openings and causes the patient to snore loudly at night and to breathe through the open mouth. The close relationship of the infected lymphoid tissue to the auditory tube may be the cause of recurrent otitis media. Adenoidectomy is the treatment of choice for hypertrophied adenoids with infection.

Tubal tonsils
Opening for Eustachian tube Gut-associated lymphoid tissue (GALT) Is located in the mucosa of the intestine.

Function:
Protects the body from ingested pathogens.
Peyer's patches of ileum Lymphatic nodules of appendix

Peyer's patch and M cells
A summary diagram showing that antigens in the gut lumen are bound by M cells and undergo transcytosis into their intraepithelial pockets where dendritic cells take up the antigen, process it, and present it to T helper cells. B lymphocytes stimulated by the Th cells differentiate into plasma cells secreting IgA antibodies. The IgA is transported into the gut lumen where it binds its antigen on the surface of microorganisms, neutralizing potentially harmful invaders before they penetrate the mucosa.