Lymphatic System

Diffuse lymphatic tissue

Not surrounded by a capsule

Lymphatic nodules

Small lymphocytes called primary nodules

Secondary nodules

More abundant

Pale central region called germinal center

Thin, darker region called corona

Germinal center

Contains large immature lymphocytes, B cells, macrophages

Cites of B cell clonal expansion, somatic hypermutation, affinity based selection that results in production of high-affinity antibodies

Why does the germinal center appear less stained?

Predominant euchromatin in the nuclei of immature lymphocytes

Corona

Highly packed with small lymphocytes

Lymphatic tissue is responding to antigens

The presence of secondary nodules is an indication that the_________

Parenchyma of lymphatic tissue

Lymphocytes and less abundant immune cells

Storms

Connective tissue capsule and septa

Storma cells

Reticular cells, follicular dendritic cells, endothelial cells

Cells in the thymus and bursa

Epithelial-reticular cells

Provide support for lymphocyte precursors and produce critical paracrine factors influencing lymphocyte differentiation and survival

Reticular fibers

• type III collagen fibers

• Same banding pattern as collagen

• No bundles but networks

• Argyrophillic (silver stain)

• Produced by fibroblasts and reticular cells

Where are lymphocytes derived from?

Multipotent lymphoid stem cells that give rise to precursors of B cells, T cells and NK cells

Thymus and Bursa

Primary lymphoid organs

Where lymphoid cell precursors become functional and self-tolerant T and B cells

Provides cells with specific antigen receptors

Bursa

Not preset in mammals

Bone marrow

Primary lymphoid organ in mammals

Where B cell instruction occurs

Secondary lymphoid organs

Lymph nodes, spleen, MALT, etc.

Where are lymphatic organs found?

Intercalated in lymph nodes and blood circulations (spleen), beneath select surface epithelia (MALT)

MALT

Supervises tissue with high exposure to pathogens such as GI and respiratory tracts

Lymph nodes

Deal with pathogens that succeeded in crossing epithelial barriers and invaded deeper tissues

Spleen

Looks for pathogens that having violated all barriers circulate freely in blooD

Critical for the surveillance of the immune system

Ability of lymphocytes and other immune cells (macrophages and DCs) to circulate in lymph and blood and move back and forth into tissues

ECF from tissues

Enters blind-ended lymphatic capillaries and circulates in valves vessels similar to veins called lymphatic vessels where it is called lymph

What surrounds lymph nodes?

White adipose tissue and a thin dense connective tissue capsule that gives rise to short partitions called trabeculae

Parenchyma of the lymph node

Divided into:

• peripheral dark cortex

• Central pale medullary

Cortex of lymph nodes

Dense mass of lymphatic tissue containing nodules of the secondary type and the paracortical region

Paracortical region

Non-modular lymphatic tissue located between the nodules and the medulla

Medulla

Non-nodule lymphatic tissue arranged as branding cords called medullary cords

Sinuses

Interconnecting channels making up the lymph nodes

Endothelium-lined spaced used for lymph circulation

Subsapsular sinuses

Afferent lymphatic vessels delivered here

Located between node’s capsule and cortex

Send lymph to trabecular sinuses

Path of lymph in the lymph nodes

Afferent lymph vessels > subcapsular sinuses > trabecular sinuses > medullary sinuses

Lymph leaving

From medullary sinuses leaves the LN through efferent lymph vessels that emerge at the hilium of the LN

High endothelial venues (HEVs)

Venues leaving nodules

Lined by simple cuboideal or columnar endothelial cells

Posses receptors from lymphocytes called homing receptors

Homing receptors

Signal lymphocytes to leave the circulation and migrate into the lymph node parenchyma

Cortical nodules

Rich in B cells

Paracortex

Populated by T cells and DCs

Germinal centers of secondary nodules

Sites of B cells Provide support activation and generation of memory cells

B cells found in all stages of differentiation into plasma cells

Follicular dendritic cells

Stromal cells located in germinal centers

Multiple, thin, hair-like branching of cytoplasmic processes that interdigitate between B cells in the germinal centers

Important for generation of memory B cells

Visualizing lymphocytes in LNs

With H&E all lymphocytes look the same

Lymphocytes and other immune cells express cell-type specific proteins, use of antibodies specific for those markers would allows for identification via immunofluorescence (IF) or immunohistochemistry (IHC)

Confocal microscope

Enables reconstruction of the image for all fluorochromes

Swine lymph nodes

Medullary tissue is found in cortex and medulla

Cortical tissue is concentrated in the center of the organ

Hemal nodes

Lymph node-like structures intercalated int eh blood circulation of ruminants

Lack medullary region

Found in sublumbar ara along vena Cava and aorta

Birds

Lack lymph nodes

Have abundant modular and diffuse lymphatic tissue associated with many organs

No lymph or hemal nodes

LN Functional considerations

• sites their pathogens and their products are concentrated and exposed to immune cells

• Sites of lymphocyte activation, clonal expansion, differentiation as well as sites of generation of memory cells

• Chances for immune cells to be exposed to antigens are increased because lymph circulation in the sinus system is slow due to presence of the reticular meshwork

• Sites for lymphocyte sequestration (HEVs) from blood

• Major sites of phagocytosis, antibody production and killing of infected cells

Spleen

Largest lymphatic organ, intercalated in the bloodstream

Consist of lymphatic tissue and specialized vascular spaces or channels

Spleen stroma

Dense connective tissue capsule form which trabeculae extend

Splenic pulp

Spleen parenchyma

Red pulp: blood vessels, large amount of immune and RBCs

White pulp: lymphatic tissue

Splenic artery

Enters spleen gives rise to smaller arteries that follow the trabeculae (trabecular arteries) > give rise to arteries of white pulp central arterioles

Periaterial lymphatic sheath (PALS)

Lymphocytes aggregate around a central artery

Roughly cylindrical configuration that conforms to the course of the central artery

T cell zones

Marginal zone of the white pulp

Rich in B cells and macrophages

May contain lymphatic nodules

Red pulp of the spleen

• splenic cords separated by the splenic sinuses

• Large # of RBCs

Splenic cords

Meshwork of reticular cells and fibers containing large number of macrophages, RBCs, lymphocytes, DCs, plasma cells and granulocytes

Where are aged or damaged macrophages and RBCs removed from the circulation via phagocytosis?

Spleen

Other sites; liver and bone marrow

Splenic sinuses

Long endothelial cells running parallel to the direction of the vessel

Immunologic functions of the spleen (mostly in white pulp)

• capture antigens from blood

• Antigen presentation by macrophages and DCs to T cells

• Activation of T cells and B cells; antibody production

Other functions of the spleen (mostly in red pulp)

• removal and destruction of senescent or damaged erythrocytes

• Retrieval of iron from hemoglobin

• Formation of blood cells (fetal life only)

• Storage of blood (Horses and dogs)

Mucosa-associated lymphatic tissue (MALT)

Beneath surface epithelia

First encounters to pathogens enter body they GI, respiratory and genitourinary systems

Sites of antigen capture and activation of B and T cells

Waldeyer’s ring

Lymphatic tissue distributed in or close to the pharynx

Include lingual tonsil, palatine tonsils, tubal tonsils and pharyngeal tonsils

Palatine tonsil

Located on depressions (tonsillar fossae) at both sides of the oropharynx

Immediately beneath the squamous stratified epithelium

Lack Afferent lymphatic vessels

Fossulae

Sites where the surface epithelium invaginated to form crypts

Peyer’s Patch

Collection of nodular and non-nodular lymph tissue embedded in intestine wall

Aggregation of immune cells cause the wall to project and form domes

Domes contain M cells

M cells (microfold)

folding of their luminal surface

sample foreign material from the lumen and deliver it via transcyotsis to APCs in M cell basal pockets

Thymus

Cranial to the hart

Capsulated non-nodular lymph organ

Trabeculae extend into thymus creating thymic lobules

Dark basophillic peripheral cortex, and pale central medulla

Lacks lymphatic nodules!!!

Epithelial reticular cells

Make up thymic stroma

Produce epithelial-like intermediate filaments (keratin)

Numerous cell-to-cell junctions

Stellate cells with thin cytoplasmic extensions

Paracrine and juxtacrine communication with thymocytes

Large, ovoid spherical nuclei

Hassall’s corpuscles

Formed by epithelial reticular cells

Acidophillic due to increasing levels of keratin

Function unknown, morphological feature important for histologial differentiation of thymus

Blood-thymus barrier

Endothelium, macrophage rich perivascular CT layer, outer sheath of epithelial reticular cells

Selective barrier that separates blood from developing T cells in the cortex

Tight junctions present

Limits access of foreign material to the cortex

Absent in cortico-medullary region where mature T cells leave thymus and enter circulation

Bursa of Fabricius

Primary lymphatic organ in birds

Seeded by lymphoid cells precursors, site of lymphocyte differentiation and regresses at the time of sexual maturity

Produces B cells

Capsule: connective and smooth muscle tissues

Parenchyma: longitudinal folds of epithelium, folds contain lymphatic tissue with dark peripheral zone and light central zone

Histological Differentiation

• thymus: parenchyma organized into lobules, individual lobules consisting of a central medulla and peripheral cortex

• LN: single medulla surrounded by single cortex, lymphatic nodules and medullary cords found in cortex and medulla

• Spleen: red pulp interrupted by white pulp, white pulp contains central artery and lymphatic nodule

Summary chart