HISTOLOGY

HISTOLOGY OF
OF
LYMPHOID
LYMPHOID ORGANS
ORGANS

INTRODUCTION
INTRODUCTION
Immune systems consists of : 4
Lymphoid organs
Heterogeneous group of motile cell types

2 components of immune systems : 3

Innate Immune System non spesific (complement,
macrophages & Neutrophils, Natural Killer cells/NK
cells) nonclonal defense mechanism
Adaptive Immune System specific (T
Lymphocytes, B lymphocytes, Antigen Presenting
Cells/APCs)

 Adaptive immune system : 4

Humoral immune response : B lymphocytes
produce antibodies phagocytosis &
digestion of bacteria by macrophages &
neutrophils leukocytes
A cell-mediated immune response : T
lymphocytes bind to surface of parasites or
virus-infected cells lyse them by secreting a
membrane-disrupting protein & a Hydrolytic
Enzyme

Lymphoid organs : 1, 3
Primary/central organs :
Thymus & Bone Marrow
responsible for development &
maturation of lymphocytes
Secondary/Pheripheral organs :
Lymph nodes, Spleen, Tonsils,
solitary nodules, Peyers Patches
of ileum, Appendix

Origin of Immune System Cells

Pluripotent hematopoetic stem cell in bone
marrow growth factors stimulation
proliferation and maturation of the cells
formed elements of the blood
Stem cell myeloid progenitor cell &
lymphoid progenitor cells
Lymphoid progenitor cells B lymphocytes
& T lymphocytes

Growth factors on hematopoietic system

G-CSF, GM-CSF, M-CSF, IL- 1, IL-3, IL-4, IL-6,
EPO, TPO etc.
Cytokines are a unique family of growth factors
messenger molecules that can communicate signals
from one cell type to another
Secreted primarily from leukocytes but also produced by
various cells of the body interleukin (IL)
IL instruct the receiving cells to proliferate, differentiate,
secrete additional cytokines, migrate or die
IL Stimulate both the humoral and cellular immune
responses, as well as the activation of phagocytic cells
The list of identified interleukins grows continuously

Origin of the main types of

lymphocytes. B lymphocytes and
natural killer lymphocytes are
formed in the bone marrow and
leave the bone marrow already
mature, to seed the secondary
lymphoid organs and transit
through the blood, epithelia, and
connective tissues. Immature CD4
and CD8 T lymphocyte
precursors are transported by the
blood circulation from the bone
marrow to the thymus, where they
complete their maturation and
leave as either CD4+ or CD8+
cells.

CLONAL SELECTION OF
LYMPHOCYTES
In bone marrow & Thymus primary
lymphoid organ
Single type receptor on Lymphocytes can
recognize all possible antigens but self
tolerance
Lymphocytes with receptors not self tolerance
are eliminated by apoptosis clonal deletion

B Lymphocytes Maturation
Bone marrow Lymphoid stem cell Pro B
cell Pre B Cell Immature/naive B cells (Ig
M) mature B Cells (Ig M + Ig D) blood
stream & circulate secondary lymphoid organ
Proliferation and maturation of B-cell responses
are mediated by cytokines

T Cells Maturation
Fetal liver/bone marrow Pre T Cell
migrate to Thymus Stage 1: T cells with
CD 4- & CD8- (double negative) Stage 2:
T Cells with CD 4+ & CD 8+ (Double
positive) Stage 3 : mature T Cell with
CD4+ or CD 8+ (single positive)

Approximate percentage of lymphocytes in

lymphoid organs1
Lymphoid
organs

T lymphocytes B Lymphocytes
%
%

Thymus

100

Bone marrow

10

90

Spleen

45

55

Lymph nodes

60

40

Blood

80

20

THYMUS
THYMUS
In superior mediastinum 1, 2
2 lobes Thin capsules septa
subdivide into incomplete lobules 1, 3
Each lobule consist of cortex &
medulla:1,3
A.Cortex :
Darker than medulla due to
large number of T lymphocytes
Also contain macrophages &
Epithelial Reticular Cells
95-98% of developing T cells
die by apoptosis in cortex
phagocytosed by macrophages

3 Types of Epithelial Reticular Cells in

Thymic Cortex 3
Type I cells
Type II cells
Type III cells
these cells completely
isolate thymic cortex &
prevent developing T Cells
from contacting foreign
antibodies

The relationship between epithelial

reticular cells and thymus
lymphocytes. Note the desmosomes and
the long processes of epithelial
reticular cells extending among the
lymphocytes

B. Medulla : 1, 3
Stain lighter than cortex less
T cells population & large
number of epithelial reticular
cells
3 types of epithelial reticular
cells in medulla :
o Type IV cells
o Type V cells
o Type VI cells Hassls
Body / Thymic Corpuscle
(found only in medulla,
cornified, even calcified,
unknown function)

Thymus vascular supply

1, 3

Blood-thymus barrier formed by continuous

cappillaries in cortex with thick basal lamina,
invested by sheath of type I epithelial reticular cells
preventing contact of developing T Cells to
blood-borne macromolecules
Self macromolecules crossed barrier to select &
eliminate T cells react with self antigens clonal
selection & clonal deletion
No barrier in medulla
T cells leave medulla via veins drainning the thymus

Hormones in thymus 1, 3
Epithelial reticular cells produce :
Thymosin
Thymopoietin
Thymulin
Thymic humoral factor
Facilitate T cell proliferation & expression of surface
markers

Other hormones influence T cells maturation :

Corticosteroids decrease T cells number in cortex
Thyroxin stimulates epithelial reticular cells to increase
thymulin production
Somatotropin promotes T cells development in thymus
cortex

THYMUS INVOLUTION4
Start after puberty
Parenchym replaced adipose
tissue and connective tissue
Decrease weights : 40 g at
puberty, 10-15 g late in life
After involution, thymus still
has its function as a maturation
place for T cells

LYMPH
LYMPH NODE
NODE
Kidney shape, encapsulated
(capsul of Conn. Tissue
Trabeculae)
Location : neck, axilla, scrotum,
blood vessels in thorax, etc 1, 2
Have Afferent lymph vessel &
Efferent lymph vessel 1
Hilum : concave depresion which
arteries & nerve enter, veins &
lymphatic vessels leave1,2
Parenchym composed of T cells,
B cells, APCs & macrophages3

 On average, naive lymphocyte spend less

than hour in circulation before homing to
another lymphoid organ
2 main ports of entry into Lymph Node :
By High Endothelial Venule (HEV)
Specialized type of post capillary venule, lined by
cuboid or high endothelial cells
Found only in secondary lymphoid organs except
spleen
Main site of B & T lymphocytes entry from blood
by diapedesis

By afferent lymph vessel Site of some memory

cells, free antigens & or antigen-loaded APC

BLOOD & LYMPH CIRCULATION OF LYMPH N

ODE

CORTEX 1, 2
o Outer Cortex
Lymphoid nodules
B cells imunocytes
Germinal center/secondary n
odules
only in response of
antigenic challenge
Reticular cells & fiber

o Inner Cortex/Paracortical
Area T cells activated &
proliferated

o Subcapsular Sinus &

intermediate/Peritrabekular
Sinus

Section of a lymph node showing the cortex and

the medulla and their primary components. B:
(1) Capsule; (2) lymphoid nodule with
germinative center; (3) subcapsular sinus; (4)
intermediate sinus; (5) medullary cords; (6)
medullary sinus; (7) trabecula. H&E stain. Low
magnification. (Courtesy of PA Abrahamsohn.)

Section of a portion of the outer cortex of a

lymph node showing the capsule,
subcapsular sinuses, diffuse lymphoid
tissue, and lymphatic nodules. H&E stain.
Medium magnification. (Courtesy of PA
Abrahamsohn.)

MEDULLA : 1, 2, 3
Medullary Cords :
B cells, plasma cells,
macrophages
Reticular cells & fiber
More irregular
trabeculae than in
cortex
Medullary Sinus
continue with
subcapsular sinus &
intermediate sinus end
up in efferent lymph
vessels

SPLEEN
SPLEEN

Largest lymphoid organ in body 3

Hilum
Capsul trabeculae
Consist of : 1, 2, 3
A. White Pulp :
Formed by :
Lymphoid nodules B cells
Peri Arterial Lymphatic
Sheath/PALS formed by T
cells surrounding A.
Centralis
Lymphoid nodules germinal
centre due to antigenic challenge

B. Marginal zone 3
Separate white pulp to red pulp
Composed of plasma cells, T cells, B cells,
macrophages, APCs
Marginal sinuses
Contain an abundance of blood antigens
plays major role in immunologic activities of
spleen

C. Red Pulp :1, 3

Consist of :
Splenic Cords / Billroths
Cords macrophages, T
cells, B cells, plasma
cells, blood cells
Splenic Sinusoids :
Endothelial cells
fusiform, elongated
Discontinuous basal
lamina

Blood Circulation of Spleen

TONSILS
TONSILS
Incompletely encapsulated aggregates of
lymphoid nodules 1
Based on location : palatine, pharyngeal, lingual
tonsils1
Produce lymphocytes1

PALATINE
PALATINE TONSILS
TONSILS
A pair, in pars oralis
pharynx1
Consist of : 1, 2, 3
Stratified squamous
Epithelium
A band of lymphoid nodule
with germinal center
Crypts :
Invagination of epithelium
10-20 crypts/tonsil
Contain food debris, dead
leucocytes, desquamated of
epithelial cells,bacteria etc

Capsule partially at the

base

The palatine tonsil consists of diffuse lymphocytes and

lymphoid nodules disposed under a stratified squamous
epithelium. One of the crypts of the tonsil is shown; the
crypts often contain dead epithelial and inflammatory cells.
B: (1) Crypt; (2) stratified squamous epithelium; (3)
lymphoid nodules; (4) diffuse lymphoid tissue; (5)
germinative center; (6) capsule; (7) mucous glands.
Hematoxylin and eosin (H&E) stain. Low magnification.
(Courtesy of PA Abrahamsohn.)

PHARYNGEAL
PHARYNGEAL TONSILS
TONSILS
Single in posterior nasopharynx1, 2
Consist of :1, 2, 3
Pseudostratified ciliated columar epithelium
Lymphoid nodules
No crypts, only shallow longitudinal infolding
called pleats
Thinner capsule than T. Palatina

LINGUAL
LINGUAL TONSILS
TONSILS
Smaller & more numerous than other tonsils
At base of tongue
Consist of :1, 2, 3
Stratified Squamous Epithelium
Lymphoid nodules germinal center
Each lingual tonsils has a single crypts

MUCOSA-ASSOCIATED
MUCOSA-ASSOCIATED LYMPHOID
LYMPHOID
33
TISSUE
/
MALT
TISSUE / MALT
Non capsulated
Lymphoid nodules in
mucosa or submucosa of GI
tract, respiratory tract,
urinary tract.
Gut-Associated lymphoid
tissue (GALT) peyers
patches (B Cells surround
by T cells & APCs)
Bronchus-associated
lymphoid tissue (BALT)
similar to peyers patches

Section of lung showing a collection of

lymphocytes in the connective tissue of
the bronchiolar mucosa, an example of
mucosa-associated lymphoid tissue
(MALT). Pararosanilinetoluidine blue
(PT) stain. Low magnification.

REFERENCES :
1.

2.
3.
4.

Basic Histology Text & Atlas , 10th ed. , L. Carlos

Junquira MD, Jose Carneiro MD, Robert O. Kelley PhD,
Lange Medical Books, Mc Graw-Hill , 2003. Pp 265
290.
Essentials of Human Histology, 2nd Edition, William J.
Krausse PhD, Little Brown & Company (Inc), 1996. Pp
197-228
Color Textbook of Histologi, 2nd edition, Gartner LP, Hiatt
JL, WB Saunders Company, Philadelphia, Pennsylvania,
2001. Pp 273-299
Consise Histology, 2nd edition, Don W Fawcett, Ronald P
Jensh, Arnold publisher, London, 2002. Pp 148-161