LYMPH AND LYMPHATIC SYSTEM

Aswathi K S1st MSc BCM

Central University of Kerala

LYMPHATIC SYSTEM A network of vessels

that collect fluid that has escaped into the tissues from capillaries of the circulatory system.

4 Parts of Lymphatic systemThe four parts of lymphatic system are

1. LYMPH2. LYMPH VESSEL3. LYMPHOID TISSUE/ LYMPHOID

ORGAN4. LYMPHOCYTES and PHAGOCYTES

1. LYMPH A clear fluid composed mainly of water, electrolytes

and some plasma proteins Transported in lymphatic pathway from lymphatic

vessels to collecting ducts and end disposed into venous blood

When blood circulates in high pressure, the fluid (plasma) portion seeps through thin capillary walls into surrounding tissue.

This interstitial fluid bathes the cells and is returned to blood through walls of venules.

The remainder enters a network of thin walled tubes called lymphatic vessels and now is called lymph

In average adult, seepage 2.9l/day

Reabsorbed by lymphatic capillaries in all body tissues where excessive tissue fluids occur.

Because of lack of pumping organ, lymph movement is largely dependent on skeletal muscle activity.

Movement normally constant and smooth, except when obstruction (small clot, tumor) occurs which tend to back up the lymph, and result in edema (fluid accumulation in tissues)

2. LYMPH VESSEL Lymphatic capillary

run parallel to blood capillaries in all body tissues and allow diffusion of fluid from intestitial spaces into lymphatic pathway.

Capillaries also responsible for absorbing short chain fatty acids in the small intestine using specialized capillaries called lacteals.

Lymphatic capillaries collecting ducts Lymphatic vessels Lymphatic trunks Lymphatic ducts.

Structurally identical to veins- vessel wall composed of 3 thin layers of tissue, and contain valves to prevent backflow.

They form specialized lymphatic organs called lymph nodes which store macrophages and lymphocytes to eliminate foreign substance in the lymph.

Larger connecting vessels converge to form Lymphatic trunks. Lymphatic trunks deliver lymph to two lymphatic ducts which eventually drain all lymph fluid back to the blood : THORACIC duct returns lymph from left side of the body to left subclavian vein, and RIGHT LYMPHATIC duct returns lymph from right part of the body to right subclavian vein

3. LYMPHOID TISSUE/ LYMPHOID ORGANS

A number of morphologically and functionally diverse organs and tissues contribute to the development of immune responses. These organs can be distinguished by function as :

1. PRIMARY LYMPHOID ORGANi. THYMUSii. BONE MARROW

2. SECONDARY LYMPHOID ORGANi. LYMPH NODEii. SPLEENiii. MALT, CALT, GALT, BALT…

1. PRIMARY LYMPHOID ORGAN Sites where immature lymphocytes

generated by haematopoesis mature and become commited to specific antigen

Only after lymphocytes mature within primary lymphoid organs are the cells immunocompetent.

T cells arise in bone marrow and mature in thymus.

In many mammals, B cells originate in bone marrow

Primary lymphoid organs are THYMUS and BONE MARROW.

1. THYMUS Flat, bilobed organ situated above the heart. Each lobe surrounded by a capsule and divided into lobules, which are separated from each other by strans of connective tissue called

trabeculae. Each lobule organized into 2 compartments:

the outer compartment cortex, and the inner compartment medulla.

Cortex is densly packed with immature T cells and medulla is sparsely packed with thymocytes.

Both medulla and cortex criss-crossed by a 3D stromal cell network of epithelial cells, dentritic cells and macrophages.

Many of the stromal cells interact physically with developing thymocytes

The function of thymus is to generate and select a repertoire of T cells that will protect the body from infection.

As thymocytes develop, an enormous diversity of T cell receptors is generated by gene rearrangement, which produces some T cells with receptors capable of recognizing antigen-MHC complexes.

Thymus induces death of cells that cannot recognize antigen-MHC complexes and those that react with self antigens.

More than 95% of thymocytes die by apoptosis in thymus before maturity.

Experiments conducted on thymectomized mice showed dramatic decrease in circulating T lymphocytes and absense of cell mediated immunity.

Thymic function is known to decline with age. Thymus reaches maximal size at puberty and atrophies, with a significant decrease in both cortical and medullary cellsand an increase in total fat content of the organ.

Average weight of thymus in human infants is 30g, and age dependent involution leaves the organ with a weight of 3g in elderly.

By the age of 35, thymic T cell generation falls to 20% of in infants and by 65, fallen to only 2%.

In one experiment, thymectomized mouse were implanted with thymus from either one day old or 33 month old mice. Mice receiving newborn thymus graft showed increased immune response than mice receiving 33 month old thymus.

ii. BONE MARROW Complex tissue which is

the site of haematopoesis and fat deposition.

Haematopoetic cells generated in bone marrow move through walls of blood vessel and enter blood stream, which carries them out of the marrow and distributes these cells to the rest of the body.

In humans and mice, it is the site of B cell origin and development

Immature B cells arise from lymphoid progenitor cells, proliferate and differentiate in bone marrow. Stromal cells in bone marrow interact directly with B cells and secrete various cytokines required for development.

Bone marrow B cells are source of 90% IgG and IgA in the plasma.

In birds B cell maturation occurs in bursa of Fabricius – a lymphoid organ associated with the gut, is the site of B cell maturation.

In cattle and sheep, primary lymphoid tissue hosting B cell maturation, proliferation and diversification in early gestation is fetal spleen.

In later gestation, this function is assumes by a patch of tissue in intestinal wall called ileal Payers patch which contain large amount of B cell and T cell.

The rabbit uses gut associated tissue, especially the appendix

2. SECONDARY LYMPHOID ORGAN

Lymph nodes and spleen are the most highly organized secondary lymphoid organs.

In addition to lymphoid follicles, they have additional distinct regions of T-cell and B –cell activity, and are surrounded by a fibrous capsule.

Less organized lymphoid tissue, collectively called Mucosa Associated Lymphoid Tissue (MALT) is found in various body sites.

MALT includes Payers patches (in small intestine), the tonsils, and the appendix as well as numerous lymphoid follicles within lamina propria of intestinal lining and in mucous membranes lining the upper airways , bronchi, and genitourinary tract.

i. LYMPH NODES Sites where immune responses

are mounted to antigens in lymph. Encapsulated bean shaped

structures containing a reticular network packed with lymphocytes, macrophages and dendritic cells.

1st structure to encounter antigen that enter the tissue spaces.

As lymph percolates through, antigen is trapped by cellular network of phagocytic cells and dendritic cells.

Ideal environment for lymphocyte to effectively encounter and respond to trapped antigen.

Lymph node can be divided into 3 centric regions: the Cortex, the Paracortex and the Medulla.

The outer most cortex contains lymphocytes(mostly B), macrophages and follicular dendritic cells arranged in primary follicles.

On antigenic challenge, primary follicle enlarges to secondary follicle with germinal centre.

Children with B cell deficiency lack primary follicles and germinal centers.

Beneath cortex, paracortex: largely populated by T lymphocytes and dendritic cells that migrated from tissues to the node.

These dendritic cells express high levels of class II MHC molecules – necessary for antigen presentation to TH cells.

Medulla is more sparsely populated with lymphoid lineage cells, and many are plasma cells actively secreting antibodies.

An antigen is carried to node by lymph, it is trapped, processed and presented with MHC molecule by the dendritic cells in paracortex, resulting in activation of TH cells.

Initial activation of B cell occur in paracortex. Activated TH cells and B cells form a small foci, with proliferating B cells at the edge of paracortex. Some B cells form plasma cells.

The foci reach maximum size within 4-6 days of antigenic challenge.

Within 4-7 days few B and TH cells move to primary follicle of cortex and interact with dendritic cells to form secondary follicle with germinal center.

Some plasma cells in germinal center move to medullary areas and many migrate to bone marrow.

The afferent lymph vessel pierce node and empty lymph to sub capsular sinuses, where the lymph percolate slowly and allow phagocytic cells and dendritic cells to trap antigen.

The lymph leaving the node is rich in antibody, which is secreted by medullary plasma cells and has 50x higher concentration of lymphocytes.

Higher concentration of lymphocyte is due to higher proliferation at lymph node.

Blood bourne lymphocyte migrate to nodes through walls of post capillary venules lined by epithelial cells , called High Endothelial Venules (HEV)

ii. SPLEEN Situated high in the left abdominal cavity, an ovoid organ. Filter blood and trap blood borne antigen: thus respond

to systemic infections. Not supplied by lymphatic vessels. Instead blood borne

antigen is carried to spleen by splenic artery. Surrounded by a capsule from which a number of

projections (trabeculae) extend into interior to form compartments.

Compartments are of two types: the RED pulp and the WHITE pulp, separated by a diffuse marginal zone.

Red pulp consist of network of sinusoids populated by macrophages, RBC and lymphocytes. It is the site where old and defective RBC are destroyed and removed.

The white pulp surrounds the branches of splenic artery, forming Periarteriolar Lymphoid Sheath(PALS) populated by T lymphocytes.

primary lymphoid follicles are attached to PALS and are rich in B cells, some of them contain germinal centers.

Marginal zone is populated by lymphocytes and macrophages.

Blood borne antigen and lymphocytes enter spleen through splenic artery, and empties into marginal zone.

In marginal zone, antigen is trapped by dendritic cell and carried to PALS.

Initial activation of B and T cells takes place in T cell rich PALS.

Dendritc cells capture antigen and present it to TH cells by class II MHC molecules. Activated TH cells activate B cells.

B cells n TH cells migrate to primary follicles in marginal zone and on antigenic challenge, they develop into charecteristic secondary follicles with germinal centers.

In germinal centers rapidly dividing B cells and plasma cells are surrounded by dense clusters of concentrically arranged lymphocytes.

iii. MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT)

The vulnerable membrane surfaces of respiratory, digestive and urogenital tracts are defended by group of organized lymphoid tissue called MALT.

Secondary lymphoid tissue associated with respiratory epithelium is Bronchus Associated Lymphoid Tissue (BALT)

That of digestive tract is called Gut Associated Lymphoid Tissue (GALT)

MALT ranges from loose, barely organized clusters of lymphoid cells in lamina propria of intestinal villi to well organized structures such as Payers patches in intestinal lining.

MALT also includes tonsils and appendix.

MALT contains large population of plasma cells, greater than concentration in spleen, lymph node and bone marrow combined.

Outer mucosal epithelial layer contains intraepithelial lymphocytes (IEL)

Lamina propria contains large number of B cells, plasma cells, TH cells and macrophages in loose clusters.

Antigen transport from lumina to underlying mucosa associated lymphoid tissue carried out by M cells.

M cells have deep invaginations and antigens in the intestinal lumen are endocytosed into vesicles that are transported from luminal membrane to underlying pocket membrane.

Vesicle fuse with pocket membrane delivering antigen to lymphocytes and antigen presenting cells.

Antigen hence transported result in activation of B cells that secrete IgA, which combat many type of infection at mucosal sites.

CUTANEOUS ASSOCIATED LYMPHOID TISSUE (CALT)

Skin is the largest organ of the body and plays an important role in defense mechanism as anatomical barrier.

Epidermal layer of cells composed of specialized keratinocytes, which produce cytokines that induce local inflammatory reaction.

Scattered in epidermis are langerhans cells, which undergo maturation and migrate to lymph nodes where they act as potent activators of naïve TH cells.

Epidermis also contains intra epidermal lymphocytes, which are mostly T lymphocytes,

The dermal layer of skin contains scattered T cells and macrophages.

4. LYMPHOCYTES AND PHAGOCYTES

T CELLS B CELLS NATURAL KILLER CELLS MONOCYTES AND MACROPHAGES MAST CELLS DENDRITIC CELLS GRANULOCYTIC CELLS: Neutrophil.

Eosinophil, Basophil FOLLICULAR DENDRITIC CELLS

FUNCTIONS OF LYMPHATIC SYSTEM

Immunity fluids from all capillary beds are filtered immune cells stand ready to respond to

foreign cells or chemicals encountered Lipid absorption

Lacteals in small intestine absorb dietary lipids Fluid recovery

absorbs plasma proteins and fluid (2 to 4 L/day) from tissues and returns it to the bloodstream interference with lymphatic drainage leads to

severe edema

Any questions?