UNIVERSITY OF ZAMBIA

SCHOOL OF MEDICINE
• HUMAN HISTOLOGY

• The Lymphatic System

Dr. Mukape Mukape:

- BSc.HB, MBChB, MSc in Progress (UNZA)
- Diplomatic Practice, Protocol and Public
Relations (ZIDIS)
- Senior Resident Medical Officer (SRMO)
at Ministry of Health (MoH), Zambia
- Staff Development Fellow (SDF), SOM,
UNZA.

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 Introduction
• The lymphatic system and the immune system
are interrelated

• The lymphatic system comprises of:

1. Lymphatic vessels (lymph capillaries, lymphatic
ducts)
2. Lymphoid organs

• Lymphatic vessels carry a clear fluid called lymph

(tissue fluid, interstitial fluid) directly towards
the heart
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 Introduction
• The lymphoid organs are interconnected by
lymphatic vessels and contain a diverse
population of leukocytes that make the immune
system
• Hence, these organs filter lymph and blood
against micro-organisms as it passes through
them
• The immune system therefore provides defense
or immunity against infectious agents ranging
from viruses to multicellular parasites

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• The cells of the immune system has the ability
to distinguish "self" (the organism's own
molecules) from "nonself" (foreign substances)
• These include soluble molecules as well as
molecules present in viruses, bacteria, and
parasites
• It also acts to destroy microorganisms or other
cells (such as virus-infected cells, cells of
transplanted organs, and cancer cells)
• On occasion, the immune system of an individual
reacts against its own normal body tissues or
molecules, causing autoimmune diseases

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 Functions of the Lymphatic System
1. Responsible for the removal of interstitial fluid from
tissues and returns it to the heart. Interference with
lymphatic drainage leads to woody hard oedema
2. Absorbs and transports fatty acids and fats as
chylomicrons in chyle from the digestive system
3. Transports leukocytes to and from the lymph nodes
into the bones
4. Lymph transports antigen-presenting cells (APCs) such
as dendritic cells to the lymph nodes where an
immune response is stimulated. Hence, removes and
exposes antigens to the immune system
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 Antigens
• An antigen is a molecule that is recognized by cells of
the immune system
• Antigens may consist of:
 soluble molecules (such as proteins, polysaccharides,
and nucleoproteins) or
 molecules belonging to whole cells (bacteria,
protozoa, tumor cells, or virus-infected cells)
• The cells of the immune system do not recognize and
react to the whole antigen molecule but instead react
to small molecular domains of the antigen known as
antigenic determinants or epitopes
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 Antibodies
• An antibody is a glycoprotein that interacts
specifically with an antigenic determinant
(epitope)
• Antibodies belong to the immunoglobulin (Ig)
protein family
• Antibodies are secreted by plasma cells that
arise by proliferation and terminal
differentiation of clones of B lymphocytes whose
receptors recognize and bind specific epitopes

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 Classes of Antibodies

• The main classes of immunoglobulins in

humans are:
1. IgG
2. IgA
3. IgM
4. IgE
5. IgD

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 Components of the Immune System
A. INNATE IMMUNITY B. ACQUIRED IMMUNITY
1. Epithelial barriers of the skin, - Also called adaptive immunity
GIT, GUT, and respiratory tract
2. Leukocytes: 1. Humoral immunity
- Neutrophils - B Lymphocytes
- Eosinophils - These form plasma cells which
- Monocytes later release antibodies
- Macrophages
- Dendritic cells (APCs) 2. Cell-mediated immunity
3. Mast cells - T Lymphocytes
4. Natural killer cells
5. Complement system

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 Components of the Immune System

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Humoral immunity destroy extracellular microbes while cell
mediated immunity destroy intracellular immunity

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 Organs of the Lymphatic System
• The organs of the lymphatic system can be
broadly divided into:
1. Conducting system
2. Lymphoid tissue
• The conducting system carries the lymph and
consists of tubular vessels that include:
- Lymph capillaries
- Lymphatic vessels e.g. right lymphatic duct
and thoracic duct
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 Lymphoid Organs
• Divided into:
A. Generative (primary) organs: where
lymphocytes express antigen receptors and mature
1. Thymus
2. Bone marrow

B. Peripheral (secondary) lymphoid organs: where

adaptive immune responses develop
1. Lymph nodes
2. Spleen
3. Mucosa Associated Lymphoid Tissue (MALT)

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• The cells of the immune system:
1. Are distributed throughout the body in the
blood, lymph, and epithelial and connective
tissues
2. Are arranged in small spherical nodules called
lymphoid nodules found in connective tissues
and inside several organs
3. Are organized as differently sized organs called
lymphoid organs

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• Lymphoid nodules and mucosa-associated lymphoid
tissue (MALT) may be considered a lymphoid organ
• MALT is isolated cells of the immune system found in
the mucosa of the digestive system, respiratory
system, the reproductive system and the urinary
system
• Those found in the GIT include:
1. Tonsils
2. Peyer's patches
3. Vermiform appendix
• The wide distribution of immune system cells and
the constant traffic of lymphocytes through the
blood, lymph, connective tissues, and lymphoid
organs provide the body with an elaborate and
efficient system of surveillance and defense
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 The Lymphatic Vessels
• The lymphatic capillaries originate in the
various tissues as thin, closed-ended
vessels that consist of a single layer of
endothelium and an incomplete basal
lamina
• Lymphatic capillaries are held open by
numerous microfibrils of the elastic fiber
system, which also bind them firmly to the
surrounding connective tissue
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 Lymph Capillaries

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 Structure of a Lymphatic Capillary

Arrows show discontinuous

basal lamina

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• The thin lymphatic vessels gradually converge
and ultimately end up as two large trunks:
- The thoracic duct and
- The right lymphatic duct
• The thoracic duct empty into the junction of the
left internal jugular vein with the left subclavian
vein
• The right lymphatic duct empty into the
confluence of the right subclavian vein and the
right internal jugular vein

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• Interposed in the path of the lymphatic vessels are
lymph nodes
• With rare exceptions, lymphatic system is found in
almost all organs
• Examples of exceptions include:
1. CNS (Brain and spinal cord)
2. Cornea
3. Cartilage
4. Epidermis of the skin
• The lymphatic vessels have a structure similar to that
of veins except that they have thinner walls and lack
a clear-cut separation between layers (intima,
media, adventitia)

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• They also have more numerous internal valves
• The lymphatic vessels are dilated and assume a
nodular, or beaded, appearance between the valves
• As in veins, lymphatic circulation is aided by the
action of external forces
• These include:
1. Contraction of the surrounding skeletal muscle
(most important factor)
2. The negative intrathoracic pressure during
inspiration
• These forces act discontinuously, and unidirectional
lymph flow is mainly a result of the presence of
many valves in these vessels

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• Contraction of smooth muscle in the walls of
larger lymphatic vessels also helps to propel
lymph toward the heart
• The structure of the large lymphatic ducts
(thoracic duct and right lymphatic duct) is
similar to that of veins, with reinforced smooth
muscle in the middle layer
• The adventitia is relatively underdeveloped
• Like arteries and veins, large lymphatic ducts
contain vasa vasorum and a rich neural
network
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 MALT

Bronchial Mucosa Peyer’s Patches of the GIT

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Peyer’s Patches and the Microfold (M) Cells

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 Waldeyer’s Lymphatic ring
• Several aggregation of lymphoid tissue constitute
this ring in relation to the naso-oropharyngeal
isthmus
• Consists of:
1. Palatine tonsils on the laterally on both sides (left
and right)
2. Pharyngeal tonsil posteriorly
3. Tubal tonsils laterally and above, next to opening of
the auditory tube into the nasopharynx
4. Lingual tonsils inferiorly over posterior part of the
dorsum of the tongue

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 Tonsils

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 Tonsil

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 Vermiform Appendix

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 The Thymus

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• The thymus is a lymphoepithelial organ
located in the mediastinum
• It attains its peak development during youth
• Whereas the other lymphoid organs
originate exclusively from mesenchyme
(mesoderm), the thymus has a dual
embryonic origin
• Its lymphocytes arise in the bone marrow
from cells of mesenchymal origin

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• These invade an epithelial primordium
(endoderm) that has developed from the
endoderm of the 3rd pharyngeal pouch
• The thymus has a CT capsule that penetrates
the parenchyma
• The capsule divides it into incomplete
lobules, so that there is continuity between
the cortex and medulla of adjoining lobules

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• Each lobule has:
- A peripheral dark zone
known as the cortex
- A central light zone
called the medulla (L.
medius, middle)

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• The cortex is composed of
an extensive population of:
- Immature or
undifferentiated T cells
(T cell precursors)
- Dispersed epithelial
reticular cells
- Macrophages

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• The medulla contains:
- Epithelial reticular cells
- Mature or differentiated T lymphocytes
- Thymic corpuscles or Hassall corpuscles, which
are characteristic of this region, although their
function is unknown
• These corpuscles contain flattened epithelial
reticular cells that are arranged concentrically
and are filled with keratin filaments
• They sometimes calcify

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 Vascularisation of the Thymus
• Arterioles and capillaries in the thymus are
surrounded by processes of epithelial reticular
cells
• Thymus capillaries have a nonfenestrated
endothelium and a very thick basal lamina
• This makes these blood vessels particularly
impermeable to proteins
• This prevents most circulating antigens from
reaching the thymus cortex, thus creating the so-
called thymic–blood barrier
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• The thymus has no afferent lymphatic vessels and
does not constitute a filter for the lymph, as do
lymph nodes
• The few lymphatic vessels encountered in the
thymus are all efferent
• These are located in the walls of blood vessels and
in the connective tissue of the septa and the
capsule

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 Vascular Supply of the Thymus
Arteries
• Mainly from branches of internal thoracic and inferior thyroid
arteries
• These also supply the surrounding mediastinal CT
• A branch from the superior thyroid artery is sometimes
present

Veins
• Thymic veins drain to left brachiocephalic, internal thoracic
and inferior thyroid veins
• Occasionally directly into the superior vena cava
• One or more veins often emerge medially from each lobe of
the thymus to form a common trunk opening into the left
brachiocephalic vein

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 Blood supply of the Thymus Gland

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 Lymphatic Drainage of the Thymus
• Has no afferent lymphatics
• Efferent lymphatics arise from the medulla and
corticomedullary junction
• Drain through the extravascular spaces in
company with the arteries and veins that supply
the thymus
• Thymic lymphatic vessels end in the
brachiocephalic, tracheobronchial and
parasternal nodes

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 Functions of the Thymus
1. Site of terminal differentiation and selection of T
lymphocytes
- The main function of the thymus is the site of T-
lymphocyte differentiation and the selective removal of
T cells reactive against self-antigens, a key part of
inducing central self-tolerance
- This along with regulatory T cells prevents
autoimmunity
- The thymus reaches its maximum development in
relation to body weight immediately after birth
- Undergoes involution after attaining its greatest size
in puberty
- But continues to produce lymphocytes until old age
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 Section of the Thymus of an elderly adult. Severe atrophy of the parenchyma was
replaced by adipose tissue

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 Child vs Adult Thymus

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2. The thymus is also an endocrine gland secreting
four main hormones:
- Thymosin alpha
- Thymopoietin
- Thymulin
- Thymus humoral factor
These hormones seem to be paracrine secretions
acting in the thymus

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 Lymph Nodes
• Lymph nodes are distributed throughout the body
along the course of the lymphatic vessels
• The nodes are found in the:
- Axilla
- Groin
- Along the great vessels of the neck
- Thorax
- Abdomen, especially in mesenteries
• Lymph nodes constitute a series of in-line filters that
are important in the body's defense against
microorganisms and the spread of tumor cells
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 Lymph Nodes

*
Superficial groups
-Cervical
-Axillary
-Inguinal
Deep groups
-Tracheobronchial *
-Aortic
-Iliac
Drainage
-Superior R 1/4 of body: Right
lymphatic duct (green) *
-The rest: thoracic duct *

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• All this lymph, derived from tissue fluid, is filtered
by at least one node before returning to the
circulation
• Lymph nodes are elongated or kidney-shaped
organs
• They have a convex surface that is the entrance site
of lymphatic vessels and a concave depression, the
hilum
• The hilum is through which arteries and nerves
enter and veins and lymphatic vessels leave the
organ
• A CT capsule surrounds the lymph node, sending
trabeculae into its interior
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 Structure of a Lymph Node

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 Structure of a Lymph Node

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• The most common cells of lymph nodes:
- Lymphocytes (B and T)
- Macrophages and other APCs
- Plasma cells
- Reticular cells
- Follicular dendritic cells are present within the
lymphoid nodules
• The different arrangement of the cells and of the
reticular fibril skeleton that supports the cells
creates two regions, a cortex and a medulla
• The cortex can be subdivided into an outer cortex
and an inner cortex or paracortical region
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 Cortex
• Consists of the following components:
1. A diffuse population of cells composed mainly of T
lymphocytes and reticular cells, macrophages and APCs
2. Lymphoid nodules, with or without germinative centers,
formed mainly by B lymphocytes
3. Areas of loose lymphoid tissue situated immediately
beneath the capsule, called the subcapsular sinuses
- Lymph, containing antigens, lymphocytes, and APCs,
circulates around the wide spaces of these sinuses after
being delivered into these channels by the afferent
lymphatic vessels
4. Intermediate or radial sinuses that run between lymphoid
nodules
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 Regions of a Lymph Node
• 3 functional regions:
a. Cortex (C)
b. Paracortex (P)
c. Medulla (M)
• Connective tissue of the capsule (CT)
completely surrounds each lymph node
and extends as several trabeculae (T)
throughout the lymphoid tissue
• Major spaces for lymph flow are
present in this tissue under the capsule
and along the trabeculae
• A changing population of immune cells
is suspended on reticular fibers
throughout the cortex, paracortex, and
medulla
• Lymphoid nodules (LN) are normally
restricted to the cortex, and the
medulla is characterized by sinuses
(MS) and cords (MC) of lymphoid tissue

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 Regions of a Lymph Node
1. Capsule
2. Lymphoid nodule with
germinative center
3. Subcapsular sinus
4. Intermediate sinus
5. Medullary cords
6. Medullary sinus
7. Trabecula

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 Lymph Node Cortex

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 Medulla
• The medulla has two components:
1. Medullary cords
- Are branched cordlike extensions of dense lymphoid tissue
that arise in the inner cortex
- They contain primarily B lymphocytes and often plasma
cells and macrophages
2. Medullary sinuses
- These are dilated spaces that separate medullary cords
- They contain lymph, lymphocytes, macrophages, and
sometimes even granulocytes if the lymph node is draining
an infected region
- These sinuses arise from the intermediate sinuses
- Join at the hilum delivering the lymph to the efferent lymph
vessel of the lymph node

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 Lymph Node Medulla

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 Lymph Circulation in the Lymph Node
• Afferent lymphatic vessels cross the capsule and
pour lymph into the subcapsular sinus
• Lymph then passes through the intermediate
sinuses and, finally, into the medullary sinuses
• During this passage, the lymph infiltrates the
cortex and the medullary cords
• The lymph is finally collected by efferent
lymphatic vessels at the hilum
• Valves in both the afferent and efferent vessels
aid the unidirectional flow of lymph
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 The Spleen

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 The Spleen
• The spleen is surrounded by a capsule of dense CT
• From the capsule emerge trabeculae
• These divide the parenchyma, or splenic pulp, into
incomplete compartments
• Large trabeculae originate at the hilum, on the
medial surface of the spleen
• These trabeculae carry nerves and arteries into the
splenic pulp as well as veins that bring blood back
into the circulation
• Lymphatic vessels that arise in the splenic pulp also
leave through the hilum via the trabeculae
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 Histology of the Spleen

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 Splenic Pulp (Spleen Parenchyma)
• The spleen is composed of a network of reticular
tissue that contains reticular cells, many
lymphocytes and other blood cells, macrophages,
and APCs
• The splenic pulp has two components:
1. White pulp
2. Red pulp
• These names derive from the fact that on the
surface of a cut through an unfixed spleen, white
spots (lymphoid nodules) are observed within a dark
red tissue that is rich in blood

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• The white pulp consists of:
1. Periarterial lymphatic sheath (PALS)
which consist of T-lymphocytes
2. Lymphoid nodules which consist of B-
lymphocytes

• Red pulp consists of:

1. Splenic cords (Billroth's cords)
2. Blood sinusoids

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 White Pulp
• The splenic artery divides as it penetrates the hilum
• It branches into trabecular arteries of various sizes that
follow the course of the connective tissue trabeculae
• When they leave the trabeculae to enter the parenchyma,
the arteries are immediately enveloped by a sheath of T
lymphocytes, the periarterial lymphatic sheath (PALS),
which is part of the white pulp
• These vessels are known as central arteries or white pulp
arteries
• After coursing through the parenchyma for variable
stretches, the PALS receive large collections of
lymphocytes , mostly B cells, forming lymphoid nodules

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 Splenic Pulp

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 White Pulp

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 Red Pulp
• The red pulp is composed of splenic cords and
blood sinusoids
• The splenic cords contain a network of reticular cells
supported by reticular fibres (collagen type III)
• The splenic cords contain:
- T and B lymphocytes
- Macrophages
- Plasma cells
- Many blood cells (erythrocytes, platelets, and
granulocytes)
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 Red Pulp

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• The splenic cords are separated by
irregularly shaped wide sinusoids
• The endothelial cells that line sinusoids
have large nuclei bulging into sinusoidal
lumens called stave cells
• Their long axes are parallel to the long axes
of the sinusoids
• These cells are enveloped in reticular fibers
set primarily in a transverse direction, much
like the hoops on a barrel

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 Red Pulp

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 Closed vs Open Blood Circulation in the Spleen
• The manner in which blood flows from the arterial
capillaries of the red pulp to the interior of the
sinusoids has not yet been completely explained
• Some investigators suggest that the capillaries
open directly into the sinusoids
- This form a closed circulation in which the blood
always remains inside the vessels
• Others maintain that the prolongations of the
penicillar arteries open into the splenic cords
- Then blood passes through the space between the
cells to reach the sinusoids (open circulation)
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 Blood Flow in the Spleen

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 Functions of the Spleen

1. Sequestration and phagocytosis

2. Immunological function
3. Extra-medullary haemopoiesis
4. Blood pulling and storage of RBCs and platelets

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 Functions of the Spleen
1. Sequestration and Phagocytosis
- Has abundant phagocytic cells e.g. macrophages
- The spleen thus is an important organ that acts to defend
against antigens (microorganisms) that reach the blood
circulation
- Is a site of destruction of effete and aged erythrocytes and
other abnormal blood cells e.g. target cells, spherocytes
e.t.c
- It also removes Howell-Jolly bodies (basophilic remnants
of DNA), Heinz bodies (denatured Hb inside RBCs due to
oxidative stress) and Pappenheimer bodies which contain
sideroblastic granules from the RBCs by ‘pitting’ and the
cells are returned in the circulation
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2. Immunological function
- As is true of all other lymphoid organs, the spleen is
a production site of activated lymphocytes
- These are delivered to the blood
- The spleen reacts promptly to antigens carried in the
blood
- It is thus an important blood filter and antibody-
forming organ (due to plasma cells)
- Has about 25% of the body’s T-lymphocytes and
15% of B lymphocytes
NB: The spleen filter blood unlike other lymphoid
organs that filter lymph

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3. Extra-medullary haemopoiesis
- Pluripotential stem cells are present in the spleen
- The spleen is a vital extramedullary haemopoietic
organ during fetal life
- Also during severe haematological stress e.g.
haemolytic anaemia due to any cause (inherited or
acquired), the pluripotential stem cells proliferate
and form blood cells

4. Blood pulling and storage of RBCs and platelets

- RBCs can be stored in the spleen and released into
the circulation when needed
- This function is better marked in animals than man
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 Summary of Major Lymphoid Organs

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 Applied Anatomy
1. Autoimmune diseases
2. Cancer metastasis
3. Splenomegaly
4. Asplenia
5. Splenectomy (auto/surgical)
6. Hard woody oedema conditions e.g. lymphatic
elephantiasis, Kaposi sarcoma
7. Appendicitis
8. Appendicectomy
9. Tonsillitis
10.Pharyngeal adenoids
11.Lymphadenopathy
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 Medical Application of the Spleen
• Although the spleen has numerous important
functions in the body, it is not essential to life
• In some situations the spleen must be removed
(splenectomy) e.g.:
- Abdominal trauma that results in rupture of the
spleen capsule
- Haemolytic anaemias (inherited or acquired)
- Platelet disorders e.g. immune thrombocytopenic
purpura
- Hypersplenism which results from splenomegaly
of any cause resulting in pancytopenia
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• In this case other organs (e.g., the liver) take over
some of the functions of the spleen
• The risk of infection may be higher in a
splenectomized individual, especially those due to
encapsulated bacteria
• The infection is called Overwhelming Post-
Splenectomy Infection (OPSI)
• Thus vaccination against these micro-organisms is
needed e.g. Streptococcal pneumoniae,
Haemophilus influenza type B and Neisseria
meningitidis
• They are also given monthly benzathine penicillin G
given as prophylaxis
• Other encapsulated bacteria include: Salmonella
typhi, E.coli, and Klebsiella pneumoniae
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• For the splenic macrophages to remove
encapsulated bacteria, the bacteria needs to be
opsonized by either the antibody IgG or the
complement protein called C3b
• Capsules made of polysaccharides permit
bacteria to evade phagocytosis by macrophages
alone, since only proteins are directly
recognized by macrophages in phagocytosis
• So humoral immunity in form of IgG and the
innate immunity in form of the complement
proteins is the human immune system’s
response against bacterial capsules

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 Causes of Splenomegaly
• The causes can be grouped on the basis of the pathogenic
mechanism
• These are:
1. Increased function of the spleen due to:
a. Removal of defective RBCs
b. Immune hyperplasia
- Response to infection (viral, bacterial, fungal, parasitic)
- Disordered immuno-regulation
c. Extra-medullary haemopoiesis
2. Abnormal blood flow due to:
- Portal hypertension leading to cirrhosis of the liver
3. Infiltration due to:
a. Metabolic diseases
b. Benign and malignant infiltrations
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 Causes of Massive Splenomegaly
1. Hyper-reactive Malarial Splenomegaly (HMS)
- Old term was Tropical splenomegaly (chronic
malaria)
2. Myeloproliferative disorders:
- Myelofibrosis
- Chronic myeloid leukemia (CML)
3. Kala-azar leishmaniasis (Visceral leishmaniasis)
4. Gaucher’s disease (rare)

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Lymphatic filariasis or elephatiasis

• Wuchereria bancroft

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 Tonsillitis

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• Ascites: accumulation of • Hydrocele: accumulation
interstitial fluid in of interstitial fluid in
peritoneal cavity tunica vaginalis

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 The End!

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