DR Salamah Alwahsh: Lymphoid System

Lymphoid System: Primary
Dr Salamah Alwahsh
Lymphatic vessels, Bone marrow, Thymus
Lymphoid System Lecture Outline
• Introduction
• Primary lymphoid organs
• Bone marrow
• Thymus
• Secondary lymphoid organs
• Lymph nodes
• Spleen
• MALT
Function of the Lymphoid System
• The main purpose of the lymphoid system is to
detect and inactivate foreign substances, such as:
• Invading microorganisms
• Cells of transplanted organs
• Foreign materials (like pollen)
• Cancer cells
• Lymph also brings nutrients from blood vessels to
cells and picks up waste products.
• All lymphoid tissues and organs are involved

in production of lymphocytes
Lymph vascular system
• Collects fluid from tissues and returns it to the blood vascular system.
• Consists of
- blind-ended capillaries (lymphatic capillaries) connected to venous
vessels
- lymphatic vessels
- lymphatic ducts
6
Lymph (Lymphatic Fluid)
• Formed when interstitial fluid seeps into lymphatic

vessels. Also contains lymphocytes, proteins, and
sometimes bacteria or metastatic tumor cells.
• Composition varies in different body regions.
Usually lymph is clear, but lymph draining the gut
(called “chyle”) is milky and contains a lot of
triglycerides.
• Lymphatic vessels eventually merge together and
empty into the blood circulation via the thoracic
duct and right lymphatic duct.
8
Small lymphatic vessel & venule
9
Medium sized lymphatic vessel
10
• Lymphatic vessels ultimately converge as two large trunks: the
thoracic duct and the right lymphatic duct, which empty lymph
back into the blood
• The thoracic duct connects with the blood circulatory system near
the junction of the left internal jugular vein with the left subclavian
vein, whereas the right lymphatic duct enters near the confluence of
the right subclavian vein and the right internal jugular vein
• The structure of these largest lymphatic vessels is similar to that of
small veins
• The adventitia is relatively underdeveloped, but contains vasa
vasorum and a neural network.
• Besides gathering interstitial fluid as lymph and returning it to the blood,
the lymphatic vascular system is a major distributor of lymphocytes,
antibodies, and other immune components that are carried through
many organs to and from lymph nodes and other lymphoid tissues
11
Right
lymphatic
duct
Thoracic
duct
Medical application
• Lymphatics and larger lymphatic vessels are clinically
important because (among other reasons) they facilitate
the spread of pathogens, parasites, and malignant cells
in the body
• Surgical removal of lymph nodes (standard procedure to
determine the occurrence of cancer metastasis) can
disrupt the lymphatic drainage and produce swelling or
lymphedema, in tissues of the affected region
13
Stroma of Lymphoid Organs
• The stroma of all lymphoid organs except the

thymus is composed of reticulin fibers.
• The stroma of the thymus is composed of cell
processes of epithelial reticular cells.
Reticular fibers (type III collagen) forming a network. These
fibers are argyrophilic (stainable with silver stains).
Cells of the Lymphoid System
• Lymphocytes
• B lymphocytes
• T lymphocytes
• Natural killer (NK) cells
• All lymphocytes have surface receptors
that recognize infected cells.
All lymphocytes look the same!*
• You can’t reliably tell the type

of lymphocyte by looking
under a microscope.
• You have to use a technique
called flow cytometry to look
for markers (molecules) on
the surface of the cells.
• B cells, T cells and NK cells
have different markers on
their cell surfaces.
* Pretty much. Sometimes T cells and NK cells are bigger and have
little granules in the cytoplasm.
More Cells of the Lymphoid System
• Antigen-presenting cells:
• Macrophages
• Dendritic cells
• Other blood cells:

• Mast cells
• Neutrophils
• Monocytes
• Eosinophils
Ridiculously Oversimplified Immunology
There are two main ways lymphocytes fight intruders

(like bugs): humoral and cellular immunity.
Humoral immunity
B cells turn into plasma cells, which make antibodies.
Antibodies coat and eliminate bugs.
Cellular immunity
T cells turn into cytotoxic T cells (which kill cells
infected with bugs) and helper T cells (which help
other cells do their jobs).
Primary (Central) Lymphoid Organs
Lymphocytes arise, differentiate and become
immunocompetent in primary lymphoid organs.
There are two primary lymphoid organs:
• Bone marrow
All lymphocytes arise in the bone marrow.
B cells (memory + plasma cells (specific
immunity)) and NK cells mature in the bone
marrow.
• Thymus
T cells mature here.
What do B cells do in
primary and secondary
lymphoid organs?
• B lymphocytes and natural

killer cells are formed and
mature in bone marrow.
• They then leave bone marrow,
populate ‫ يقطنوا‬in secondary
lymphoid organs, and
recirculate through blood,
epithelia, and connective
tissue
What do T cells do in
primary and secondary
lymphoid organs?
• Immature T-cell precursors

originate in the bone marrow.
• They then leave bone marrow
and travel through blood to
the thymus.
• They finish maturing in the
thymus and leave as CD4+ and
CD8+ cells (this will make
more sense next year!)
Normal bone marrow biopsy
Thymus
• Bilobed structure located in mediastinum
• Primary/ central lymphoid organ for T cell differentiation
• A main function of the thymus is induction of central
tolerance, which along with regulatory T cells prevents
autoimmunity (self- vs. non-self recognition)
• The thymus has a vascularized connective tissue capsule
that extends septa into the parenchyma, dividing the
organ into many incompletely separated lobules
• Lobules have 2 regions:
• Cortex is peripheral and dark basophilic staining.
• Medulla is central and lighter staining.
Lobe
Septae
Lobules
Thymus, low power

Cortex
Medulla
Thymus, medium power

Cells of the Thymus
T lymphoblasts (thymocytes)
• T cells in the cortex are in various stages of differentiation,
and numerous macrophages
• T cells in the medulla are mature.
Thymic epithelial reticular cells
• Have certain features of both epithelial and reticular cells
• Present in both the cortex and medulla
• Abundant cytoplasm, large lightly-staining nuclei and long
cytoplasmic processes attached to processes of adjacent cells
by desmosomes and occluding junctions.
• together with the vascular endothelial cells and pericytes,
forms a blood-thymus barrier preventing unregulated
exposure of thymocytes to antigens
Thymus, high power: T cells in the cortex
Thymus, high power: T cells in the medulla
Thymus, high power: epithelial reticular cell
Medulla of the
thymus with Hassall
corpuscles.
Hassel corpuscle (closely-packed, concentric reticular cells)

Large aggregates of thymic epithelial cells (TECs), sometimes concentrically
arranged, called Hassall corpuscles
Up to 100 μm in diameter, thymic corpuscles are unique to the medulla
Their cells secrete several cytokines that control activity of local dendritic
cells, including factors promoting development of regulatory T cells for
peripheral tolerance
Thymus, high power: post-
capillary venule
mature T lymphocytes exit the

thymus by passing through the
walls of venules and efferent
lymphatics in this region
T Cells in the Cortex
• T cell precursors from the bone marrow enter the

thymus in the subcapsular region
• In the outer cortex, T cells undergo active
proliferation
• In the deeper cortex, T cells undergo “selection”
• If they can’t bind well enough to cell receptors
• or if they bind too well to “self” cells, they die
• So: many T cells are produced, but most (97%) die.
T Cells in the Medulla
• The remaining T cells survive and migrate to

the medulla.
• Cells in the medulla include mature T cells and
epithelial reticular cells.
• Hassall’s corpuscles are made of degenerating
epithelial reticular cells and keratin filaments.
Found only in medulla. Function unknown.
T Cells in the Blood
• Mature T cells leave the thymus and enter the blood.

• Arterioles and capillaries in cortex are surrounded by
epithelial reticular cells with tight junctions, forming
a blood-thymus barrier which excludes ‫ يمنع‬most
circulating antigens
• Thymus has no afferent lymphatics, and does not
filter lymph like a lymph node does.
Development and Involution of the Thymus
• The thymus is well-developed before birth.

• The thymus is heaviest at puberty.
• After puberty, it involutes ‫ تضمحل‬but never
completely disappears.
• In old age, the thymus is composed mainly of
connective tissue and fat, but it is still capable of
producing lymphocytes.
The thymus in elderly people consists mostly of
fat and connective tissue

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Lymphoid System: Primary

• All lymphoid tissues and organs are involved

• Formed when interstitial fluid seeps into lymphatic

• The stroma of all lymphoid organs except the

• You can’t reliably tell the type

• Other blood cells:

There are two main ways lymphocytes fight intruders

• B lymphocytes and natural

• Immature T-cell precursors

Thymus, low power

Thymus, medium power

Hassel corpuscle (closely-packed, concentric reticular cells)

mature T lymphocytes exit the

• T cell precursors from the bone marrow enter the

• The remaining T cells survive and migrate to

• Mature T cells leave the thymus and enter the blood.

• The thymus is well-developed before birth.

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