LYMPHATIC SYSTEM

HISTOLOGY
Throughout history, it has been noted that people who recover from certain
diseases such as chickenpox, measles, and mumps become resistant (i.e.,
immune) to the same disease. Another long-standing observation is that
immunity is specific—that is, immunity to chickenpox does not prevent infection
with measles. We also now recognize that the immune system can react against
itself, causing autoimmune diseases such as autoimmune hemolytic anemia,
some forms of diabetes mellitus, and autoimmune thyroiditis (Hashimoto’s
thyroiditis).
Lymphoid system composed of organs, whose tissue and cells play an important
role in immunity; a protective response of the internal environment of the body
against microorganisms and foreign substances, and found either in a form of:

1. Individual structures (reticular tissue) as in lymph node or spleen that is

composed of reticular fibers and fixed cells.
2. Free cells, as lymphocytes, granulocytes and mononuclear phagocytic system.
3. Antigen-presenting cells, which present in addition to lymphoid tissue in skin.

There are two types of lymphoid organs:

1. Central lymphoid organs: as thymus and bone marrow, where lymphoid cells
precursors undergo antigen-independent proliferations to develop as T-
lymphocytes (in thymus) or B-lymphocyte (in bone marrow).
2. Peripheral lymphoid organ: as spleen, lymph node, tonsil, peyer’s patches and
lymphatic nodules in the wall of digestive, urinary, respiratory and reproductive
system, where lymphocytes migrate to them after leaving central lymphoid
organs.
Lymphatic Vessels
Lymphatic vessels are the route by which cells and large molecules pass from the
tissue spaces back to the blood. Lymphatic vessels begin as networks of blind
capillaries in loose connective tissue.
They are most numerous beneath the epithelium of skin and mucous membranes.
These vessels remove substances and fluid from the extracellular spaces of the
connective tissues, thus producing lymph. Because the walls of the lymphatic
capillaries are more permeable than the walls of blood capillaries, large
molecules, including antigens and cells, gain entry more readily into the lymphatic
capillaries than into blood capillaries.
Lymphocytes circulate through both lymphatic and blood vessels. The circulation
of lymphocytes through the lymphatic vessels and the bloodstream enables them
to move from one part of the lymphatic system to another at different stages in
their development and to reach sites within the body where they are needed.

Diffuse Lymphatic Tissue and Lymphatic Nodules:

The alimentary canal, respiratory passages, and genitourinary tract are guarded
by accumulations of lymphatic tissue that are not enclosed by a capsule.
Lymphocytes and other free cells of this tissue are found in the lamina propria
(subepithelial tissue) of these tracts. This form of lymphatic tissue is called diffuse
lymphatic tissue or mucosa-associated lymphatic tissue (MALT)because of its
association with mucous membranes
These cells are strategically located to intercept antigens and initiate an immune
response. After contact with antigen, they travel to regional lymph nodes, where
they undergo proliferation and differentiation. Progeny of these cells then return
to the lamina propria as effector B and T lymphocytes.
The importance of diffuse lymphatic tissue in protecting the body from antigens is
indicated by two factors:
• The regular presence of large numbers of plasma cells, especially in the lamina
propria of the gastrointestinal tract, a morphologic indication of local antibody
secretion.
• The presence of large numbers of eosinophils, also frequently observed in the
lamina propria of the intestinal and respiratory tracts, an indication of chronic
inflammation and hypersensitivity reaction

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Lymphatic nodules:
• Small collections of densely packed lymphocytes, that appear strongly stained
by hematoxylin in histological section, due to their basophilic nuclei.
• The inner region of the nodules shows a less stained area called germinal
center, which contains activated lymphocytes, with pale staining nuclei and large
amount of cytoplasm, most lymphocytes in germinal center are in mitosis.
• These nodules with germinal center called secondary nodules, while those
without germinal center called primary nodules.
• There is certain lymphoid tissue present in association with body organs:

1. MALT (Mucosa Associated Lymphoid Tissue).

2. GALT (Gut Associated Lymphoid Tissue).
3. BALT (Bronchus Associated Lymphoid Tissue) in submucosa of bronchus.

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Thymus:
• Central lymphoid organ, situated in the mediastinum at the level of great
vessels of the heart.
• Development: dual embryological origin, its lymphocytes arise from
mesenchymal cells that invade an epithelial primordiam that has developed from
the endoderm of the third and fourth pharyngeal pouches.
• Structure of thymus: it is surrounded by connective tissue capsule that
penetrate the parynchyma, and divide it into lobules, each lobule has a peripheral
dark zone known as cortex, and central lighter zone called medulla, cortical and
medullary zones of adjacent lobules are continuous with each other.
• Cortex composed of extensive population of T-lymphocytes, which known also
as thymocytes, dispersed epithelial reticular cells, which called thymic nurse cells,
and few macrophages.
• The developing T-cells arise from CFU-Ls, which originate in bone marrow, as
development proceeds in the thymus, cells derived from CFU-Ls pass through a
series of developmental stages that reflected by their expression of different CD
molecules.
• Epithelial reticular cells are stellate cells with light staining oval nuclei, with one
or two nucleoli, and eosinophilic cytoplasm, each cell has cytoplasmic processes
that join to adjacent cells by desmosomes.
• Bundles of intermediate keratin filaments (tonofibril) in the cytoplasm is an
evidence of their epithelial origin.
• The processes of epithelial reticular cells envelop group of lymphocytes,
isolating them from circulating antigen and form complete covering at the
periphery of the lobules and around the blood and lymphatic vessels.
• This continuous layer of reticular cells separates thymic cortical parynchyma
from other histological component of the organ, especially blood vessels forming
blood-thymic barrier.
• Blood–thymus barrier.
The following components constitute the blood–thymus barrier between the
T cells and the lumen of cortical blood vessels, from the lumen outward:
1. The endothelium lining the capillary wall is of the continuous type with
occluding junctions. It is highly impermeable to macromolecules and is
considered a major structural component of the barrier within the cortical
parenchyma. The underlying basal lamina of endothelial cells and
occasional pericytes are also part of the capillary wall.
2. Macrophages residing in the surrounding perivascular connective tissue
may phagocytose antigenic molecules that escape from the capillary lumen
into the cortical parenchyma.
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 3. Type I epithelioreticular cells with their occluding junctions provide further
protection to the developing T cells. The epithelioreticular cells surround
the capillary wall in the cortex; with their basal lamina, they represent
another major structural component of the blood–thymus barrier.

• Six types of epithelioreticular cells are recognized on the basis of function: three
types in the cortex and three types in the medulla. Each type is designated by
roman numerals. In the cortex, the following cell types are recognized.
1. Type I epithelioreticular: cells are located at the boundary of the cortex
and the connective tissue capsule as well as between the cortical
parenchyma and the trabeculae. They also surround the adventitia of the
cortical blood vessels. It serve to separate the thymic parenchyma from the
connective tissue of the organ. The occluding junctions between these cells
reflect their function as a barrier that isolates developing T cells from the
connective tissue of the organ—that is, capsule, trabeculae, and
perivascular connective tissue.
2. Type II epithelioreticular: cells are located within the cortex. The
transmission electron microscope (TEM) reveals maculae adherents
(desmosomes) that join long cytoplasmic processes of adjacent cells. The
cell body and cytoplasmic processes contain abundant intermediate
filaments. Because of their processes, these cells are stellate. They have a
large nucleus that stains lightly with H&E because of its abundant
euchromatin. This nuclear feature allows the cell to be easily identified in
the light microscope. Type II cells compartmentalize the cortex into isolated
areas for the developing T cells.
3. Type III epithelioreticular cells are located at the boundary of the cortex
and medulla. The TEM reveals occluding junctions between sheet-like
cytoplasmic processes of adjacent cells. Like type I cells, type III
epithelioreticular cells create a functional barrier—in this case, between
the cortex and medulla.
4. Type IV epithelioreticular cells are located between the cortex and the
medulla close to type III cells. They possess sheet-like processes with
occluding junctions between adjacent cells as well as between them and
type III cells. In cooperation with type III cells, they create the barrier at the
corticomedullary junction.
5. Type V epithelioreticular cells are located throughout the medulla. Like
the type II cells located in the cortex, processes of adjacent cells are joined
by desmosomes to provide the cellular framework of the medulla and to
compartmentalize groups of lymphocytes. These nuclei contrast markedly
with the densely staining lymphocyte nuclei.
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6. Type VI epithelioreticular cells form the most characteristic feature of the
thymic medulla, the thymic (Hassall’s) corpuscles. Thymic corpuscles are
isolated masses of closely packed, concentrically arranged type VI
epithelioreticular cells that exhibit flattened nuclei. TEM studies of these
cells reveal keratohyalin granules, bundles of cytoplasmic intermediate
filaments, and lipid droplets. The cells are joined by desmosomes. The
center of a thymic corpuscle may display evidence of keratinization, not a
surprising feature for cells developed from oropharyngeal epithelium.
Thymic corpuscles are unique, antigenically distinct, and functionally active
multicellular components of the medulla. Although the function of thymic
corpuscles is not fully understood, it is thought that thymic corpuscles
produce interleukins (IL-4 and IL-7) that function in thymic differentiation
and education of T lymphocytes.
histochemical studies show that they produce thymic hormones ( e,g;
thymosin), corpuscles usually increase in size and number throughout life.

The cortex is the site of production of immature T-lymphocytes, most of

them die and removed by macrophages, only a small number will migrate
towards medulla, and through venules they will migrate to peripheral organ
as mature T-lymphocytes.
 Medulla of thymus stain lightly because of the presence of larger number of
epithelial reticular cells with only 5% of mature lymphocytes.

 The medulla contain Hassall’s corpuscle, which is the characteristic feature

of thymus, it is about 30-150 µm in diameter, degenerate and sometimes
calcified and die.

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