Histology of the Lymphatic System

Lymphatic System
 Consists of group of cells, tissues &
organs that monitor body surfaces and
internal fluid and react to potentially
harmful substances.

Examples of immune response
 Reaction against
microorganisms: bacteria,
viruses, parasites
 Reaction against tumor cells
 Allergic reactions: Hay fever
 Autoimmune reaction: Arthritis
 Graft rejection
Appendix

Terminologies
 Immune system – refers to the
lymphatic organs and lymphatic
tissues.
 Lymphatic tissues – serve as sites
where lymphocytes proliferate,
differentiate, and mature.
 Lymphocytes – the chief cellular
constituent of lymphatic tissue.

Functions of the Lymphatic System
1. Monitor body surfaces and fluid
compartments (e.g. epidermis,
mucosae, interstitium)
2. React to the presence of potentially
harmful antigens recognized as
“non-self”
3. Autoimmune diseases (rheumatoid
arthritis, type I diabetes, etc.)

Components of the Lymphatic System
A. Cells
1. Lymphocytes (B,T, natural killer)
2. APC (dendritic cells, Langerhans’ cells &
macrophages)
B. Lymphatic “tissue”– diffuse and nodular
C. Lymphatic “organs” (lymph nodes,
spleen, thymus)
D. Lymphatic vessels that carry the cells and
fluid

Classification of Lymphatic Organs
I. Primary lymphoid organs
1. Thymus
2. Bone marrow
3. Lymphatic nodules of the distal intestinal
tract
II. Secondary (effector) lymphoid
organs/tissue
1. Spleen & lymph nodes
2. Mucosal associated lymphoid tissue
(MALT)

Primary Lymphoid Organs
 The bone marrow, thymus and Peyer’s
patch are the initial “education
centers” of the immune system.
 In these organs, lymphocytes (T cells in the
thymus, B cells in bone marrow and gut)
differentiate into immunocompetent
cells (i.e. they can recognize “self” vs. “nonself”).
 This differentiation is said to be antigen-
independent.

Primary Lymphoid Organs
 The lymphocytes then enter the blood
and lymph to populate:
• epidermis and mucosae
• connective tissue
• secondary lymphoid organs

Secondary Lymphoid Organs
 This is where immunocompetent
lymphocytes differentiate into immune
effectors & memory.
 These lymphocytes then carry out their
functions in the:
• connective tissue
• secondary lymphoid organs
• mucosal surfaces lining epithelia

Secondary Lymphoid Organs
 They participate in:
• Cell mediated immunity (mostly
“cytotoxic” T cells)
• Humoral responses (production of
antibody) (B cells, also requires
“helper” T cells)

Lymphocytes in peripheral blood smear
These are B and T-cells that have undergone antigen-INDEPENDENT differentiation and
are trafficking through the bloodstream on their way to lymphoid organs/tissue.

Cytokines and chemokines (along with selectins and integrins) mediate
EXTRAvasation of lymphocytes into tissues.

MALT: intraepithelial lymphocytes: γδT-cells
(neither helper or cytotoxic): first to see antigens
U-M Histology Collection

Intraepithelial lymphocytes
Shown here in resp. epith.
Homing mediated by
“addressins” (a sort of
lymphocyte“GPS”)

LN
LYMPHOCYTES IN CONNECTIVE TISSUE:
MALT = mucosa-associated lymphoid tissue
Primary lymphatic nodule/follicle (LN)Diffuse lymphoid tissue
Lamina propria (LP) of gut shown here, but can
be found associated with mucosae anywhere in
the gut, respiratory, and genitourinary tracts.
Aggregation of lymphocytes in lamina propria or
submucosa of gut, respiratory or genitourinary

LYMPH NODE
Secondary lymphoid nodule/follicle
• Contain germinal centers
• Arise when B-lymphocytes are presented with appropriate antigen,
receive T-cell help, and then begin proliferating as lymphoblasts
• Lymphoblasts differentiate into plasma cells or memory cells.

Source Undetermined
Microfold, or “M” CELLS
Modified intestinal epithelial cells that assist in antigen presentation by
conveying macromolecules from the intestinal lumen to underlying
compartments housing lymphocytes and macrophages.

After antigen presentation and T-cell help,
activated B-cells set up germinal centers in
secondary follicles

White arrows = Golgi regionsBlack arrows indicate several plasma cells
U-M Histology Collection Junquiera and Carneiro. Basic Histology. Tent
Ed. 2003
Plasma Cells are mature B lymphocytes

Source Undetermined
Hence, associated with just
about any mucosa (GI,
respiratory, genitourinary),
one may see:
• Intraepithelial
lymphocytes (T-cells)
• Diffuse lymphoid tissue:
– B-cells
– T-cells
– APCs
• Primary nodules
• Secondary nodules
– Germinal center with
lymphoblasts and mphages

Mucosa-associated lymphatic
tissue (MALT)
 Collective term for the cells of the
immune system in the mucosa of the
respiratory, alimentary, urogenital &
mammary gland.
 Function: to augment the mechanical
& chemical barriers of surface
mucosal epithelia.

Distribution: MALT – GIT
 In the pharynx – tonsils (palatine,
lingual, pharyngeal)
 In the small intestine – aggregate
lymphoid nodules (Peyer's Patches)
 In the colon – aggregate lymphoid
nodules

MALT
 Tonsils
 Bronchus-associated lymph.
tissue (BALT)
 Gut-associated lymph. tissue
(GALT)

Tonsil – MALT of the
Oropharynx
 Aggregated lymphatic nodules in the
pharynx; often the site of an early
encounter with infectious agents and
antigens.

Low mag of a palatine or lingual tonsil

Palatine Tonsil w/ SS
non-K (arrow)
Pharyngeal Tonsil w/ Resp
epith (arrow = nodule)

Ross and Pawlina, Histology: A Text and Atlas
The palatine tonsils are paired structures made of dense accumulations of lymphatic tissue located in the
mucous membrane of the junction of the oropharynx and oral cavity. The tonsils dip down into the
underlying CT, forming crypts. There are also lingual tonsils and pharyngeal tonsils (under the roof of the
nasopharynx and around the opening of the Eustachian tubes). Key features: crypts, abundant
nodules, stratified squamous epithelium

Esophagus and trachea, monkey242

MALT – In the wall of the vagina

Micrographs of human vagina showing presence of aggregated
MALT containing numerous lymphocytes (arrows).

• Appendix (Slide 32412). 32412
Lymphoid tissues are important in the defense against ingested micro-organisms
Lymphoid tissues

Regions of
extensive
lymphoid
infiltration:
Peyer’s patches
Source Undetermined
Aggregates of
lymphoid follicles
in the ileum.

THYMUS
 It is a bilobed organ located in the
superior mediastinum.
 Functions:
 production of immunocompetent T
lymphocytes
 production of mature but naïve T cells for
peripheral tissues and circulation
 regulation of T cell maturation, proliferation
and function via secretion of hormones

CAPSULE
The thin capsule is composed of dense irregular collagenous connective
tissue (with some elastic fibers) that extends interlobular trabeculae that
incompletely subdivide the thymus into lobules.

The thymus has two tissue components: parenchyma and stroma. The
parenchyma is composed mostly of T lymphocytes in various stages of development
into mature T cells whereas the stroma is composed of special thymic epithelial
cells.

Low mag of the thymus
The cortical region
of each lobule is
separated from the
adjacent one by
fibrous capsule
but the medullary
region is shared by
all lobules
The cortex has a lot of lymphocytes, fewer in the medulla The cortex appears
darker because of the much higher number of precursor T-cells than medulla.
THERE ARE NO GERMINAL CENTERS IN THE THYMUS!

Thymus, newborn
Outer darkly staining areas (cortex) and lighter central areas (medulla).
Cortex
Medulla
Thymocytes
Medulla
Continuous capillaries, sheathed by epithelial reticular cells around each, characterizes
blood vessels in the thymus cortex and is responsible for the blood thymus barrier. Also
there are no afferent lymphatics in the thymus.

Thymus, newborn
Cortex
Mitotic figures frequently, which reflect the high proliferative rate of these cells.
epithelial reticulum cells

In the medulla, the stroma consists of prominent epithelial cells that have
large, pale-staining nuclei and substantial amounts of eosinophilic
cytoplasm. There are fewer T cells because most of them have entered the
blood stream via vessels at the corticomedullary junction.

Dark nuclei
= T-cells
Larger
nuclei =
endothelial
reticular
cells
Arrow =
Hassall’s
Corpuscle
High mag of the medulla of the thymus

With ageing in postnatal life thymus is progressively replaced by adipose
tissue. Thymic mass is reduced by INVOLUTION in adults but remnants of
thymic tissue can be identified in the anterior mediastinum.

The Thymus undergoes
a process called
THYMIC INVOLUTION, as
T cells leave the thymus to
populate other lymphoid
effector organs, the organ
shrinks, leaving only the
epithelioretucular cells
The young thymus
Thymus at puberty

THYMUS
FRAMEWORK
- EPITHELIUM
Epithelial reticulum cells
Hassall's
corpuscles
Blood-thymus barrier
in cortex

LYMPH NODE
 Lymph nodes are small bean-shaped
organs that are spread throughout the
body.
 Functions:
Filter lymph, thereby promoting
lymphocyte contact with antigen
Provides necessary microenvironment
for antigen-dependent differentiation

LYMPH NODE
 Capsule
 Cortex: lymphatic nodules, sinuses
 Paracortex
 Medulla: medullary cords & medullary
sinuses

The only lymphatic organ with both afferent and efferent lymph vessels.
*Afferent LV – convey lymph toward the node; enter on convex surface.
*Efferent LV – enter at the hilus.

Lymph nodes are surrounded by a fibrous connective
tissue capsule that enters the organ as trabeculae that define
a cortex and medulla.

The blood vessels and efferent lymphatic channel pass
through hilum

In contrast to a single efferent lymphatic channel multiple
incoming afferent lymphatic channels enter the node at
discrete intervals (arrows) in the capsule.

Beneath the capsule
is a subcapsular
sinus into which
lymph flows from the
afferent lymphatic
vessels.
The capsule and trabeculae are the source of reticulin
fibers that are found throughout the node and form the main
supporting network of the organ.

Subscapular sinus
Afferent
lymphatic
duct
Subscapular space
Capsule

Low mag of a lymph node
Cx = cortex w/ lymphatic nodules (F); M = medulla; C = CT capsule

The cortex contains lymphoid follicles which are aggregates primarily of B-lymphocytes
whereas the medulla contains medullary sinuses (arrow), plasma cells, memory B-cells,
some T-cells, and histiocytes.

A lymphatic nodule with germinal center (GC)
Lymphatic nodules, composed of a dark corona or mantle zone (B
lymphocytes) and lighter staining germinal centers, housing activated B
lymphoblasts, macrophages and dendritic reticular cells.

Predominantly B lymphocytes, around germinal center
Germinal center
Perifollicular
area
Predominantly T lymphocytes
High endothelial venules = sites where blood-borne lymphocytes enter the node.

Lymph node
Afferent
lymphatic
duct
Subcapsulary sinus
Cortex
Medulla
Large round structures (follicles),
Germinal
center,

The paracortex is the region between the cortex and
medulla, composed of T lymphocytes

Parafollicular regionParafollicular region
High endothelial venule
Part of follicle
Follicle
Typical
flat
endothelium= Site of
lymphocyte
entry into the
lymph node (one
way street)
116

The medulla of a lymph node is composed of medullary
cords interspersed between medullary sinuses.

The medullary cords are composed of plasma cells producing antibodies, their
precursors, macrophages and T helper cells. In here, the plasma cells undergo final
maturation and secrete antibodies into the lymph that is collected by efferent
lymphatic vessels.

The medullary sinuses are composed primarily of reticular fibers
(RF) providing the support framework, reticular cells (RC)
and macrophages.

Venous sinus in lymph node
Medullary cords
Venous sinus

SPLEEN
 Functions:
removal of abnormal blood cells and
particulate matter via phagocytosis
storage of iron from recycled red blood
cells
initiation of the immune responses by B
cells and T cells in response to antigens
circulating in the blood
hematopoiesis in fetus and sometimes
in adult
In horses and dogs, it functions as a reservoir from which blood can be
mobilized when needed.

SPLEEN
 Capsule: DICT, trabeculae
 White Pulp: PALS, lymphatic nodules
 Marginal zone
 Red Pulp: pulp cords, sinusoids
 Reticular fibers
 Central artery

White pulp
(lymphatic nodules)
Thick CT capsule
CT Trabeculae
Red Pulp
CT
Trabeculae
Low magnification of the Spleen

This is the spleen with white pulp (lymphocytes) surrounding a central
arteriole. The red pulp forms the bulk of the splenic parenchyma. The
splenic capsule is seen at the left, and connective tissue is also present
within the spleen as trabeculae.

CT Trabeculae
Lymphatic
nodules
White pulp
Red
Pulp

White Pulp
White Pulp
Red Pulp
Red Pulp

The red pulp is the area of spleen in between white pulp and consists of
open sinuses and cellular cords. The red pulp can be expanded markedly
by venous congestion, extramedullary hematopoiesis, or by involvement by
leukemias.

Splenic sinuses are open vascular spaces lined by a discontinuous layer of
endothelial cells and supported by a fenestrated basal lamina and reticular
fibers. The surrounding cellular splenic cords provide a tissue framework
maintaining the network of sinuses.

High mag of the splenic red pulp

The microanatomy of a sinus in a longitudinal section. The sinus is lined by a discontinuous
population of endothelial cells (curved arrows) with slit-like spaces (long arrow). The
splenic cords contain passing red blood cells, lymphocytes, monocytes, granulocytes,
in addition to resident reticular fibroblasts, plasma cells, and macrophages.

The microanatomy of a sinus in a transverse section. The curved arrow indicates an
endothelial cell. A red blood cell is moving from the cord into the sinus (long arrow).

As the body is exposed to antigens and the immune system mounts an
immune response in the form of antibody production, lymph nodules (w/
germinal centers) appear in the white pulp.

The white pulp is seen in both locations: (1) a lymphoid follicle, outlined by the dashed line and
(2) the PALS located around the central artery in which T cells are found. The lymphoid follicle
has a pale-staining germinal center (GC) in which B cells are proliferating. Note the presence of
a mantle zone (ManZ) that contains small lymphocytes and an outer marginal zone that
contains larger lymphocytes.

In the micrograph, the area of white pulp where T cells are located is readily
seen. This area consists of numerous T cells forming a kind of sheath around the
central artery; it is called the periarterial lymphoid sheath or PALS. Note the
plasma cell located in the germinal center of the lymphoid follicle.

Blood flow in the spleen. The splenic
artery enters the spleen at the hilus, then
branches into numerous arterioles that run
through the parenchyma of the spleen. When
these arterioles acquire a coating of T cells,
the arterioles are called central arteries and
the surrounding lymphoid tissue is called
the PALS, i.e., the periarteriolar lymphoid
sheath.
Smaller penicillary arteries branch off of
the central arteries and end in sheathed
capillaries

Spleen (reticulum stain)-
capsule and reticulum fibers
218

Spleen (reticulum stain)- reticulum fibers in
strands between venous (blood) sinus

Spleen
white pulp
the red pulp.
Capsule
Primary function
Of the spleen is
filtration of blood.
Spleen has no
afferent lymphatics
122
Venous sinuses, and Billroth's strands
Central artery

117 Spleen
Central artery
Follicles
Red pulp
White pulp
Penicillar arteries in marginal zone
Billroth's strandsVenous sinuses
Marginal zone

Spleen
Marginal zone
PENICILLARY ARTERIES
central artery

Litteral cells of splenic venule

Spleen
Penicillar arteries
Billroth’s
strand or
splenic
strand
Littoral cells: picket-
fence type endothelial
cells of vascular sinus

Histology of the Lymphatic System

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