Lymphatic System

Dr. Heba Kalbouneh

Associate Professor of Anatomy and Histology
Lymphatic system

The lymphatic system

consists of lymphatic
fluid, lymphatic vessels,

Dr. Heba Kalbouneh

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.
 Tonsils
Lymph is a colorless fluid that floats in the
lymphatic vessels (lymphatics). It is similar in
Thymus Spleen composition to blood plasma

Peyer patch Lymphatic vessels are thin vessels that

(small intestine)
Lymphatic
accompany arteries and veins throughout the
vessels 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.
Bone marrow

Lymph nodes
Lymphatic organs include the lymph nodes,
spleen, thymus, and red bone marrow

Dr. Heba Kalbouneh

 Fluid balance
The tissues of the body are supplied by blood Fluid similar to blood plasma, called
capillaries that bring oxygen-rich blood and interstitial fluid, leaches from these
remove carbon dioxide-rich blood. vessels into the surrounding tissue.

Around 20 liters of fluid leaves the arterial Lymphatic vessels function to drain this
capillaries every day, but only 17 liters excess fluid from the tissues as lymph
of fluid returns to the venous capillaries. and return interstitial fluid to the blood.

Dr. Heba Kalbouneh

Arterial side Venous side
 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.

Arterial side

Dr. Heba Kalbouneh

Lymph returns back to the big veins (venous
angle: the junction between subclavian and
internal jugular veins) through the Thoracic
(blind-ended)
duct and Right lymphatic duct.
Arterial side Venous side

Lymphatic
capillaries are
made of
overlapping
endothelial
cells. The
overlapping
flaps function
as a one-way
valve.

When fluid accumulates in the tissue, interstitial pressure increases pushing the flaps inward,
opening the gaps between cells, allowing fluid to flow in.

Dr. Heba Kalbouneh

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) to enter. This makes the lymphatic system a
useful way for large particles to reach the bloodstream.
Remember: lymphatic system is used, for example, for dietary fat absorption in the intestine.
Transport

Dr. Heba Kalbouneh

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.
 Tonsils
Lymphatic Organs and Tissues
Lymphocytes can be found throughout the body,
however, they aggregate in places where they are
most likely to come into contact with pathogens. Thymus Spleen

Lymphocytes are produced within the red bone

marrow and are transported via the blood vessels to Peyer patch
(small intestine)
lymphatic organs and tissues.

Lymphatic organs are divided into:

Dr. Heba Kalbouneh

Primary lymphatic organs
Bone marrow.
Thymus gland.
Are sites of Lymphocyte production, maturation,
selection
Bone marrow

Self Non-Self
Lymph node

Secondary lymphatic organs

Diffuse lymphatic tissue (lymphatic nodule).
Spleen.
Lymph nodes.
Are sites to encounter pathogens and become activated
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.

Dr. Heba Kalbouneh

Antibody- mediated 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.

Lymph node enlargement can happen in

cases of lymphoma (painless
lymphadenopathy) or infection (painful). Lymph nodes are production sites of
antibodies and activated lymphocytes
The main groups of lymph nodes include:

Name Location Associated

vessel
Axillary Armpit Axillary
nodes vein
Cubital Elbow Basilic vein
nodes
Popliteal Posterior Popliteal
nodes knee vein

Inguinal Groin Great

nodes saphenous
vein
Femoral
vein
Cervical Neck Internal
lymph jugular vein
nodes

Dr. Heba Kalbouneh

 The lymph node consists of an outer cortex and
an inner medulla

Cortex

Outer
cortex
Inner
cortex

Medulla

Cortex Medulla
Contains lymphatic No follicles
follicles
Receives lymph from Forms sinuses that lead
afferent vessels to efferent vessels at
the hilum Dr. Heba Kalbouneh
 The nodes are covered by a capsule of dense connective When lymph nodes
tissue, and have capsular extensions called the trabeculae, become enlarged, the
which provide support for blood vessels entering into the capsule is stretched and
nodes. 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.

Outer

Dr. Heba Kalbouneh

Cortex

Medulla

Paracortex
The outer cortex has lymphatic follicles that Both the macrophages, and the dendritic
mostly contain B-cells. cells trap antigens and present them on
The inner cortex (paracortex) contains their surfaces
mostly T-cells.
The medullary cords contain mostly plasma As B cells in lymphatic
cells. follicle are stimulated,
they differentiate into
Other cells in the lymph node:
plasma cells. Plasma
Macrophages
cells move to medulla
Dendritic cells
(medullary cords)
Follicular dendritic cells
Reticular cells
Outer
cortex
B-cells

Dr. Heba Kalbouneh

Paracortex
T-cells

Medulla Plasma cells

The outer cortex houses lymphatic follicles
(nodules) which are of two types:

Primary follicles: Secondary follicles: lymphoid

Dr. Heba Kalbouneh

lymphoid follicles follicles with a germinal center.
without a germinal center. Sites for B memory cell and plasma
(virgin B cells) cell generation

When activated by antigens (and T helper cells), B cells migrate to the center of the follicle,
forming a germinal center. Germinal centers are the central regions of secondary follicles where
activated B cells are proliferating (dividing by mitosis) and differentiating into plasma cells and
memory B cells. When stimulated by antigens, lymph nodes enlarge due to the formation of
germinal centers and B cell proliferation
 Macrophages and
Dendritic cells capture
antigen within tissues
and transport antigen
to secondary lymphoid
tissue
Macrophage Dendritic cell

Macrophage Dendritic cell Follicular dendritic cell

Phagocytosis Most Moderately phagocytic X

Dr. Heba Kalbouneh

phagocytic
Antigen presenting Moderate Ag- Very powerful Ag- X
(via MHC-II) presenter presenter
Location in lymph Cortex and Cortex and medulla Outer cortex
node medulla

Are antigen HOLDING cells

Holds the Ag for long time
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.

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.

Dr. Heba Kalbouneh

Medullary
Medullary
cords Hilum
sinuses
 Dr. Heba Kalbouneh
Afferent vessels
Many afferent lymphatic vessels enter the Afferent
lymph node at different points over its surface, Efferent vessel
each containing valves to prevent backflow of vessel
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
Subcapsular
sinuses converge at the hilum into the efferent
sinus
vessel.
Trabecular sinuses
Medullary sinuses
Efferent vessels
The lymph is removed from the medullary sinus via one
Sinuses are irregular spaces
or two efferent lymphatic vessels that leave the lymph
through which the lymph
node at the hilum. Valves in the vessels prevent lymph
percolates
from flowing in the wrong direction.
 Dr. Heba Kalbouneh
Lymph flow
Lymph nodes are linked together by lymphatic 1
vessels. Fluid flows through a lymph node via a
series of sinuses and lymphatic tissue 2

3
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 5
runs through trabecular (cortical) sinuses (3)
into medullary sinuses (4) and leaves through 4
the efferent lymphatic vessels (5), at the
Hilum as efferent lymph.

Efferent lymph contains lots of activated T-

lymphocytes, activated B-lymphocytes, plasma Medullary cords
cells and antibodies.

All the lymphatic sinuses are lined by a

discontinuous layer of simple squamous
endothelium
 Afferent Trabecula
lymphatic Capsule
vessel
Subcapsular sinus
Dendritic cell
Reticular cell

Trabecular
sinus

Lymphatic
follicle

Paracortex
(Thymus Macrophage
dependent zone)
Hilum

Dr. Heba Kalbouneh

Medullary
Plasma cell
sinus

Medullary cord Efferent

lymphatic
vessel Vein Artery
 Subcapsular sinus

Capsule
Afferent Trabecular
lymphatic Trabecula
sinus
vessel

Lymphatic
follicle
(B cells)

Dr. Heba Kalbouneh

T cells
(thymus dependent
zone)
Efferent lymphatic

Medullary cord Medullary

(plasma cells) sinus
Artery
Vein
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?????

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 recognise and adhere to
these endothelial cells, and squeeze
through them into the paracortex

The process of lymphocyte

recirculation is regulated by adhesion

Dr. Heba Kalbouneh

molecules on lymphocytes called
Homing receptors and their ligands This diagram of a lymph node shows the
on vascular endothelial cells called pathways that lymphocytes can take, in and
Adressins out of the lymph node.
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

Right lymphatic duct

 Is formed by right jugular and right subclavian
trunks
Drains lymph from the upper right quadrant of the
body (the right side of the head and neck, the right
side of the thorax and the right upper limb)
Empties into the junction where right internal
jugular vein joins the right subclavian vein (Rt venous
angle)
Thoracic duct (Left lymphatic duct) Cisterna
Is larger and drains lymph from the rest of the body. chyli
Originates in the abdomen as cisterna chyli
Cisterna chyli is a dilated sac at the lower end of the
thoracic duct (anterior to the bodies of L1 and L2) formed
by confluence of the right and left lumbar trunks and the

Dr. Heba Kalbouneh

intestinal trunk
Passes through the diaphragm at the aortic aperture
Empties into the junction where left internal jugular vein
joins the left subclavian vein (Lt venous angle)
 It lies high on the
Spleen upper left portion of the
The spleen is an oval-shaped intraperitoneal organ abdomen, just beneath
Approximately the diaphragm, behind
5 inches in height (12-13 cm) the stomach and above
3 inches in width (7-8 cm) the left kidney.
1 inch in thickness (2.5 cm)  It is the largest of the
Weighs 7 ounces (200gm) lymphoid organs
Lies under ribs 9 to 11

 Has a notched anterior border.

Functions Spleen
Filtration of blood
(defense against blood-
borne antigens)
 The main site Duodenum Pancreas
of old RBCs destruction.
 Production site of
antibodies and activated Lt
kidney
lymphocytes (which are
delivered directly
into the blood)
Dr. Heba Kalbouneh
The splenic artery is the largest branch
of the celiac artery. It has a tortuous
course as it runs along the upper border Liver
of the pancreas. The splenic artery then
divides into about six branches, which
enter the spleen at the hilum

The splenic artery supplies the Stomach

spleen as well as large parts of the
stomach and pancreas

Liver

Dr. Heba Kalbouneh

Pancreas
Duodenum

Lt
kidney
 The splenic vein leaves the hilum and
runs behind the tail and the body of the
pancreas. Behind the neck of the
pancreas, the splenic vein joins the
superior mesenteric vein to form the
portal vein

In cases of portal
hypertension, spleen
often enlarges from
venous congestion.

Dr. 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

Red pulp

Dr. Heba Kalbouneh

 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

The spleen is composed of parenchyma and stroma

Parenchyma: Splenic pulp
Stroma: Reticular tissue (reticular fibers and reticular cells)
There are two types of pulp in the Artery Vein
spleen:
Red pulp (rich in blood) White pulp
White pulp (lymphatic tissue)

Central
arteriole

Dr. Heba Kalbouneh

Capsule Red pulp Trabeculae
Splenic artery Blood flow through the splenic red pulp can
Divides into trabecular arteries as it take either of two routes:
enters the hilum

Trabecular arteries Open circulation: the capillaries

Follow the course of trabeculae open into the spaces of the red pulp
(splenic cords) and then the blood
Central arterioles returns to the venous system through
Are branches of trabecular arteries the wall of the splenic sinusoids
entering the white pulp. They are
surrounded by a sheath of Closed circulation: the
lymphocytes. capillaries open directly into
the splenic sinusoids (blood is
Penicillar arterioles The morphology is like penicillus enclosed by endothelium)
Each central arteriole eventually leaves
the white pulp and enters the red pulp,
losing its sheath of lymphocytes and
branching as several short straight Splenic sinusoids
penicillar arterioles that continue as
terminal capillaries.

Dr. Heba Kalbouneh

Trabecular veins

Sheathed capillaries
Some of these terminal capillaries are sheathed with APCs for Splenic vein
additional immune surveillance of blood
 White pulp (lymphoid tissue) When the lymphatic sheath
 Constituting 25% of the spleen, the white pulp is expands to incorporate the
responsible for the immunological (lymphatic) follicles, the central arteriole is
function of the spleen. displaced to one side and acquires
 The white pulp contains: an eccentric position in the follicle
Periarteriolar lymphatic sheaths (PALS): but is still called the central
tightly packed T cells arranged in cylindrical sheaths arteriole.
around central arterioles Secondary follicle
Central arteriole
With germinal center
Lymphoid follicles: spherical aggregations of B
cells scattered throughout the PALS
Primary (unstimulated) follicles contain resting
(inactive) B cells
Secondary (stimulated) follicles contain activated B Red pulp White pulp

cells in a central region (germinal center)

Splenic nodules (Malpighian corpuscles)

Note: These follicles have the same structural

organization as those found in lymph nodes

Dr. Heba Kalbouneh

Function: The lymphocytes and phagocytes monitor
the blood for foreign antigens and respond in a Production of antibodies and
similar way to those in the lymph nodes. activated lymphocytes (which are
delivered directly into the blood)
Red pulp (blood filled) Red pulp
Constituting 75% of the spleen, the red pulp is
responsible for the hematological (circulatory)
function of the spleen.
The red pulp contains :
Splenic cords (Billroth’s cords): consist of all cells
between the sinusoids in the red pulp (reticular cells,
macrophages, plasma cells, lymphocytes, RBCs,
platelets, other leukocytes)

Splenic sinusoids: are blood- filled spaces located

throughout the red pulp. They have large, dilated,
irregular lumens and large pores (spaces between the
endothelial cells)

1. The endothelial cells (stave cells) are elongated,

fusiform cells that lie parallel to the long axis of
the vessel
2. The cells lie side by side around the vessel but
not joined by any type of intercellular junctions
3. The endothelial cells are supported by highly
discontinuous basal lamina (forms bars and
encircles the sinusoid)
Function: Destruction of worn-out RBCs and platelets Dr. Heba Kalbouneh
.
 Penicillar arteriole
Macrophage
Dr. Heba Kalbouneh

Plasma cell
Sheathed capillaries
(macrophages)
Neutrophil

Lymphocyte

Erythrocyte

Red pulp
Reticular cell

Splenic sinusoid Splenic cord Note: When B cells in the primary follicles are
(Closed circulation) (Open circulation)
exposed to Antigen, they proliferate and
differentiate to plasma cells and move toward
the red pulp.
 Note the wide
gaps between
endothelial
cells which
allow for
movement of
entire cells
from cords to
sinuses

In this route plasma and all the formed elements of blood must Macrophage
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
RBC
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 Endothelial
Cell
Deformed or less pliable RBCs cannot squeeze effectively from the (stave cell)
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

amino acids
Galactose exposed pool of
blood

Induce phagocytosis of RBCs

Dr. Heba Kalbouneh

Hemoglobin is broken into Heme and Globin Iron: carried by transferrin to bone
marrow (used again)
Bilirubin: excreted by liver bile
Schematic view of the blood circulation and the structure of the
spleen, from the trabecular artery to the trabecular vein.
 Marginal zone sinuses
 Located between the white and the red The following events occur at the
pulp marginal zone:

The spaces between these sinuses are 1- APCs sample the material travelling
wide (2-3um) in blood searching for antigens

2- Macrophages attack microorganisms

It is here the blood- borne antigens and present in the blood
particulate matter have their first free
access to the parenchyma of the spleen
Lymphocytes come into contact with APCs, if they
recognize their Ag-MHC complex, the lymphocytes
initiate immune response within the white pulp

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

Dr. Heba Kalbouneh

 The blood flow in the spleen goes from splenic artery to trabecular
Functions of the spleen: artery to central arteriole, and upon leaving the white pulp, the blood
flows through penicillar arterioles and terminal sheathed capillaries to
It has circulatory as well as the splenic sinusoids, and back to veins of the pulp, trabecular veins
lymphatic functions and the splenic vein
Blood cell production: During
Penicillar Sheathed
the fetal life, blood cells are Lymphatic
arterioles capillary
produced in the spleen follicle
Blood storage: a small quantity
of blood is stored in the sinusoids Splenic
sinusoid
of the red pulp
Central
RBC destruction: most worn-out arteriole
or damaged red blood cells are Red pulp
destroyed in the spleen (some in vein
the liver and bone marrow). They PALS
are phagocytized by macrophages
Defense mechanism: Trabecular
macrophages phagocytize vein
microbes that have penetrated the
Trabecular
blood. Antigens in the blood
artery
activate B and T cells residing in

Dr. Heba Kalbouneh

the spleen, triggering immune
response

Production of antibodies and activated lymphocytes

(which are delivered directly into the blood) Splenic artery Splenic vein
Lymph node Spleen
Multiple, small Single, large
Along the course of lymphatic Intra-abdominal
vessels
Filters lymph Filters blood
Covered by fascia Covered by peritoneum

Dr. Heba Kalbouneh

Has afferent vessels No afferent vessels
Cortex and medulla White pulp and red pulp
Contains Lymphatic sinuses Contains Blood sinuses
Diffuse lymphatic tissue (lymphatic nodules)
 Is formed by aggregations of lymphatic tissue
 Is found in various mucosal sites of the body

Dr. Heba 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 Lymphatic
to the external environment. nodules

 It can therefore be referred to as:

MALT is populated by:

Mucosa-Associated Lymphatic Tissue (MALT) T cells
 These aggregations are not encapsulated B cells
 MALT can be found in the following locations: Plasma cells
Palatine tonsils Macrophages
Lingual tonsils
Pharyngeal tonsils Each of which is well situated to
Gut-associated lymphoid tissue (GALT) encounter antigens passing through
Bronchus-associated lymphatic tissue (BALT) the mucosal epithelium
Because lymphocytes have prominent
basophilic nuclei and very little cytoplasm,
Collectively the MALT is one of the lymphoid tissue packed with such cells
largest lymphoid organs, containing up usually stains dark blue in H&E stained
to 70% of all the body’s immune cells. sections
Tonsils are large, irregular masses of lymphoid tissue
Function of tonsils: Protect the body from inhaled and ingested pathogens.

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 Nasal cavity
atrophy from the
age of seven.
Hypertrophied regions of
pharyngeal tonsils
resulting from chronic
inflammation are called
adenoids.

Lingual tonsils
Dr. Heba Kalbouneh
Are located on the posterior 1/3 of the tongue.
Palatine tonsils Lymphatic
nodules
Are covered by stratified Non keratinized stratified Tonsillar crypts
squamous epithelium. squamous epithelium
The surface area of each is
enlarged with 10-20
tonsillar crypts (deep
invaginations )
Many lymphoid nodules
around the crypts
Has an underlying
capsule (partial capsule)

Palatine tonsils Capsule

Pus in tonsillar crypts Dr. Heba Kalbouneh
 Peyer's patches of ileum
Gut-associated lymphoid tissue (GALT)
Is located in the mucosa of the intestine.

Examples:
1- Peyer's patches of ileum
2- Lymphatic nodules of appendix

Function:
Protects the body from ingested pathogens.

Lymphatic nodules of appendix

Dr. Heba Kalbouneh

 Bronchus-associated lymphatic tissue (BALT)
Is located in the mucosa of the bronchioles.

Function:
Protects the body from inhaled pathogens.

Dr. Heba Kalbouneh

Thymus  Within the thymus, immature T-cells develop,
differentiate, and multiply, as well as gaining their
antigen specificity and immune tolerance to the
body’s own tissues.

 The thymus is a bi-lobed gland located in the

anterior mediastinum, posterior to the sternum and
anterior to the trachea.

 It is large in the newborn and young child

From puberty onwards, it gradually becomes
replaced by fat.

Dr. Heba Kalbouneh

Fully formed and functional at birth, the
thymus remains large and very active in T-
cell production until puberty during which it
normally undergoes involution, with
decreasing lymphoid tissue mass and
cellularity and reduced T cell output
may be involved with the decline of immune function
in the elderly
The thymus is also part of the endocrine system.
 The thymus has a double embryonic origin Lobules

Endoderm and Mesoderm

Originates from the Hematopoitic origin

embryo’s third pair of Immature T lymphocytes
pharyngeal pouches (T lymphoblasts)
circulating from the bone
marrow to invade and
unique thymic proliferate in thymus
epithelial cells during its development.

The thymus has a connective tissue capsule that

extends septa, dividing the organ into many
incomplete lobules.

Each lobule has an outer darkly basophilic cortex

surrounding a more lightly stained medulla.
Medulla Cortex

Note: Cells of the medulla are less

The staining differences reflect the much greater densely packed than in the cortex
density of lymphocytes in the cortex than the
medulla Dr. Heba Kalbouneh
The cortex contains:
1. Immature T cells (T lymphoblasts,
thymocytes) (in various stages of
differentiation and maturation)
2. Macrophages
3. Unique thymic epithelial cells (TECs)

As T cells mature, they

migrate to the medulla

The medulla contains:

1. Fewer and more mature lymphocytes.
2. Macrophages
3. Dendritic cells (APCs)
4. Unique thymic epithelial cells (TECs)
5. Large aggregates of TECs called
Hassall corpuscles

Hassall corpuscles are unique to the thymic

medulla

Dr. Heba Kalbouneh

Up to 100 μm in diameter
Are concentric aggregates of squamous
cells with central keratinization (acidophilic)
Tend to grow larger with age
Thymic Epithelial Cells (TECs) (Epithelial reticular cells) Develop from endoderm
1- Form a stroma to which macrophages and Form a network of cells bound
developing lymphocytes attach instead of together by desmosomes
reticular fibers

2- Line the capsule and septa and surround all

blood vessels in the cortex
TECs
Form a blood-thymus barrier preventing
antigens in the blood from making contact with

Dr. Heba Kalbouneh

the developing T cells (in cortex)

3- Envelop groups of T cells that are multiplying

and maturing (in cortex) Developing
Lymphocytes
4- Act as APCs, expressing MHC class II and
MHC class I molecules (in cortex) Endothelial
cell
Blood vessel
5- Express many specialized proteins specific to Basement
membrane
cells of other organs, tissue specific antigens (in
medulla) Perivascular CT
with macrophage
6- Secrete hormones that promote the
TEC
differentiation of T cells (endocrine thymus)
Thymosin, Thymopoietin Developing Lymphocytes
Dr. Heba Kalbouneh
 Immature T cells arriving in
the thymus do not yet express
CD4, CD8, or a TCR.

These cells populate the

cortex and begin to proliferate
and express TCR proteins,
CD4 and CD8

TECs in the cortex present the

Dr. Heba Kalbouneh

developing T cells with
peptides on both MHC class I
and class II molecules

Developing T cells whose TCRs or whose CD4 or CD8 cannot recognize MHC molecules
undergo apoptosis before they leave the cortex
This interaction determines whether the newly made TCR proteins of these cells are functional.

A cell’s survival depends on whether its TCRs can recognize and bind MHC molecules properly
(positive selection)

80% of the developing T cells die in the cortex (undergo apoptosis) and are removed by the
macrophages
 The surviving cells (T cells with
functional TCRs) enter medulla

In the medulla, T cells encounter antigens

presented on both TECs and dendritic cells.

Here the focus is on removing T cells whose TCRs

bind self-antigens

A cell’s survival depends on a cell not binding to

MHC molecules with self-antigens
(negative selection)

Dr. Heba Kalbouneh

Self-antigens presented here are those from
proteins specific for many tissues other than the
thymus (tissue specific antigens )

T cells that bind MHCs containing self antigens undergo

apoptosis and are removed by the macrophages
(if survive autoimmune response!!!)

Only about 2% of all developing T lymphocytes pass

both the positive and negative selection tests and survive
to exit the thymus as immunocompetent T cells.
 To summarize:
Positive selection occurs in the cortex and allows survival
only of T cells with functional TCRs that recognize MHC
class I and class II molecules. Negative selection occurs in the
medulla and allows survival only of T cells that do not bind
self antigens presented on dendritic cells and TECs there.

CD8
TCR
T cells undergo positive and negative selection
processes to ensure that they will not react with
healthy cells of the body. Cytotoxic T cell

Depending on which class of MHC they interacted with, most of

these lymphocytes will have stopped expressing either CD8 or CD4,
and become either helper T cell or cytotoxic T cell

Fully mature T cells (immunocompetent T-cells) leave the medulla

via venules and efferent lymphatic vessels

They migrate from the thymus to specific regions in the lymph

CD4
nodes (paracortex), the spleen (PALS), and diffuse lymphatic TCR
tissues, where they reside and are responsible for
cell-mediated immune responses
Dr. Heba Kalbouneh T Helper cell
After maturation in primary lymphoid organs, B and T cells circulate to the peripheral secondary
lymphoid organs (the MALT, the lymph nodes, and the spleen). Lymphocytes do not stay long in
the lymphoid organs; they continuously recirculate through the body in connective tissues, blood,
and lymph.

Choices of lymphocytes:
1- If no antigen is present: lymphocytes routinely
enter and leave secondary lymphoid tissues
2- If antigen enters the secondary lymphoid tissue:
Lymphocyte proliferation in response to antigen
occurs within the lymphoid tissue.
Lymphocytes continuously circulate After several days, antigen-activated lymphocytes
between the lymph and blood until they begin leaving the lymphoid tissue.
encounter their antigen

Because of the constant mobility of lymphocytes and APCs, the cellular locations and
microscopic details of lymphoid organs differ from one day to the next. However, the relative
percentages of T and B lymphocytes in these compartments are relatively steady

Lymphocytes in the marrow and thymus of a newborn infant not yet exposed to antigens are

Dr. Heba Kalbouneh

immunocompetent but naive and unable to recognize antigens. After circulating to the
various secondary lymphoid structures, lymphocytes are exposed to antigens on APCs and
become activated, proliferating to produce a clone of lymphocytes all able to recognize that
antigen
Advantage sof lymphocyte recirculation:

Dr. Heba Kalbouneh

Lymphocyte recirculation enables the
limited number of naïve lymphocytes
in an individual that are specific for a
particular antigen to search for that
antigen throughout the body

It ensures that particular lymphocytes are

delivered to particular tissue

Recirculation of naïve lymphocytes:

recirculate through secondary lymphoid
organs

Recirculation of activated lymphocytes:

migrate to peripheral tissues at sites of
infection