Download histology of lymphoid organs lymphoid organs

HISTOLOGY OF
LYMPHOID ORGANS
INTRODUCTION
• Immune systems consists of : 4
– Lymphoid
L
h id organs
– Heterogeneous group of motile cell types
• 2 components of immune systems : 3
– IInnate
t Immune
I
System
S t Æ non spesific
ifi (complement,
(
l
t
macrophages & Neutrophils, Natural Killer cells/NK
cells)) Æ nonclonal defense mechanism
– Adaptive Immune System Æ specific (T
Lymphocytes, B lymphocytes, Antigen Presenting
C ll /APC )
Cells/APCs)
• Adaptive immune system : 4
– Humoral immune response : B lymphocytes
produce antibodies Æ phagocytosis &
digestion of bacteria by macrophages &
neutrophils leukocytes
– A cell-mediated
ll
di t d immune
i
response : T
lymphocytes bind to surface of parasites or
virus-infected
virus
infected cells Æ lyse them by secreting a
membrane-disrupting protein & a Hydrolytic
Enzyme
y
Lymphoid organs : 1, 3
• Primary/central organs :
Thymus & Bone Marrow Æ
responsible for development &
maturation of lymphocytes
y p y
• Secondary/Pheripheral
y
p
organs
g
:
Lymph nodes, Spleen, Tonsils,
solitary nodules, Peyer’s Patches
of ileum, Appendix
Origin of Immune System Cells
• Pluripotent hematopoetic stem cell in bone
marrowÆ growth factors stimulation Æ
proliferation and maturation of the cells Æ
formed elements of the blood
y
progenitor
p g
cell &
• Stem cell Æ myeloid
lymphoid progenitor cells
• Lymphoid progenitor cells Æ B lymphocytes
& T lymphocytes
Growth factors on hematopoietic
p
system
y
• G-CSF, GM-CSF, M-CSF, IL- 1, IL-3, IL-4, IL-6,
EPO TPO etc
EPO,
etc.
• Cytokines are a unique family of growth factors Æ
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 Æ interleukin (IL)
– IL instruct the receiving cells to proliferate, differentiate,
secrete additional cytokines
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
lymphocytes.
natural killer lymphocytes are
formed in the bone marrow and
lea e the bone marrow
leave
marro already
alread
mature, to seed the secondary
lymphoid organs and transit
th
through
h the
th blood,
bl d epithelia,
ith li andd
connective tissues. Immature CD4–
and CD8– T lymphocyte
precursors are transported
t
t d by
b the
th
blood circulation from the bone
marrow to the thymus, where they
complete
l t their
th i maturation
t ti andd
leave as either CD4+ or CD8+
cells.
CLONAL SELECTION OF
LYMPHOCYTES
• In bone marrow & Thymus Æ primary
lymphoid organ
• Single type receptor on Lymphocytes can
recognize all possible antigens Æ but self
tolerance
• Lymphocytes with receptors not self tolerance
are eliminated
li i t d by
b apoptosis
t i Æ clonal
l l deletion
d l ti
B Lymphocytes Maturation
• Bone marro
marrow Æ Lymphoid
L mphoid stem cell Æ Pro B
cell Æ Pre B Cell Æ Immature/naive B cells (Ig
M)Æ mature B Cells (Ig M + Ig D) Æ blood
stream & circulate Æ secondary lymphoid organ
• Proliferation
lif i andd maturation
i off B-cell
ll responses
are mediated by cytokines
T Cells Maturation
• Fetal liver/bone marrow Æ Pre T Cell Æ
migrate
g
to Thymus
y
Æ Stage
g 1: T cells with
CD 4- & CD8- (double negative) Æ Stage 2:
T Cells with CD 4+ & CD 8+ (Double
positive) Æ Stage 3 : mature T Cell with
CD4+ or CD 8+ (single positive)
Approximate percentage of lymphocytes in
l
lymphoid
h id organs1
Lymphoid
organs
Thymus
T lymphocytes B Lymphocytes
%
%
100
0
Bone marrow
10
90
Spleen
45
55
L
Lymph
h nodes
d
60
40
Blood
80
20
THYMUS
• In superior mediastinum 1, 2
• 2 lobes Æ Thin capsules Æ septa Æ
subdivide into incomplete lobules 1, 3
• Each lobule consist of cortex &
,
medulla:1,3
A.Cortex :
• Darker than medulla Æ due to
large number of T lymphocytes
• Also contain macrophages &
E ith li l Reticular
Epithelial
R ti l Cells
C ll
• 95-98% of developing T cells
p p
in cortex Æ
die byy apoptosis
phagocytosed by macrophages
B. Medulla : 1, 3
– Stain lighter than cortex Æ less
T cells population & large
number
b off epithelial
ith li l reticular
ti l
cells
– 3 types of epithelial reticular
cells in medulla :
o Type IV cells
o Type V cells
o T
Type VI cells
ll Æ Hassl’s
H l’
Body / Thymic Corpuscle
(found only in medulla,
cornified, even calcified,
unknown function)
Thymus vascular supply1, 3
• Blood-thymus barrier Æ formed by continuous
cappillaries in cortex with thick basal lamina,
invested by sheath of type I epithelial reticular cells
Æ preventing contact of developing T Cells to
blood-borne macromolecules
• Self macromolecules crossed barrier Æ to select &
eliminate T cells react with self antigens Æ 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
Th i humoral
h
l factor
f t
Æ Facilitate T cell proliferation & expression of surface
markers
• Other hormones influence T cells maturation :
– Corticosteroids Æ decrease T cells number in cortex
– Thyroxin
h
i Æ stimulates
i l
epithelial
i h li l reticular
i l cells
ll to increase
i
thymulin production
– Somatotropin
p Æ ppromotes T cells development
p
in thymus
y
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 NODE
• Kidney shape, encapsulated
(capsul of Conn. Tissue
ÆTrabeculae)
• 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
½ hour
h
iin circulation
i l i before
b f
homing
h i 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
F d only
l iin secondary
d
lymphoid
l
h id organs except
spleen
• Main site of B & T lymphocytes entry from blood Æ
by diapedesis
– By afferent lymph vessel Æ Site of some memory
cells, free antigens & or antigen-loaded APC
BLOOD & LYMPH CIRCULATION OF LYMPH
NODE
CORTEX 1, 2
o Outer Cortex
• Lymphoid nodules
– B cells Æ imunocytes
– Germinal center/secondary
nodules Æ only in response
of antigenic challenge
• Reticular cells & fiber
o IInner Cortex/Paracortical
C t /P
ti l
Area Æ 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)
i t
intermediate
di t sinus;
i
(5) medullary
d ll
cords;
d (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.
tissue,
nodules H&E stain
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 Æ
continue with
subcapsular
p
sinus &
intermediate sinus Æend
up in efferent lymph
vessels
SPLEEN
•
•
•
•
Largestt lymphoid
L
l
h id organ in
i body
b d 3
Hilum
Capsul Æ trabeculae
Consist of : 1, 2, 3
A. White Pulp
p:
• Formed by :
– Lymphoid nodules Æ B
cells
– Peri Arterial Lymphatic
Sheath/PALS Æ formed by
T cells surrounding A.
Centralis
• Lymphoid nodules Æ germinal
centre due to antigenic
challenge
B. Marginal
i l 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 Æ
plays
l
major
j role
l in
i immunologic
i
l i activities
ti iti off
spleen
1 3
C Red
C.
R dP
Pulp
l :1,
• Consist of :
ƒ Splenic Cords / Billroth’s
Billroth s
Cords Æ macrophages, T
cells, B cells, plasma
cells, blood cells
ƒ Splenic Sinusoids :
Endothelial cells
fusiform, elongated
Discontinuous basal
lamina
Blood Circulation of Spleen
TONSILS
• Incompletely encapsulated aggregates of
lymphoid nodules 1
• Based on location : p
palatine,, pharyngeal,
p y g , lingual
g
tonsils1
• Produce lymphocytes1
PALATINE TONSILS
• A pair, in pars oralis
pharynx1
1 2,
2 3
• Consist
C i off : 1,
– Stratified squamous
p
Epithelium
– A band of lymphoid nodule
with germinal center
– Crypts
C t :
• Invagination of epithelium
• 10-20 crypts/tonsil
• Contain food debris, dead
leucocytes, desquamated of
epithelial cells,bacteria etc
– C
Capsule
l Æ partially
ti ll att the
th
base
The palatine
Th
l ti
t il consists
tonsil
i t off diffuse
diff
l
lymphocytes
h t and
d
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 TONSILS
• Single in posterior nasopharynx1, 2
1 22, 3
• Consist
C i t off :1,
– Pseudostratified ciliated columar epithelium
– Lymphoid nodules
– No crypts, only shallow longitudinal infolding called
pleats
l
– Thinner capsule than T. Palatina
LINGUAL TONSILS
• Smaller & more numerous than other tonsils
• At base of tongue
• Consist of :1,, 2,, 3
– Stratified Squamous Epithelium
– Lymphoid
L
h id nodules
d l Æ germinal
i l center
t
– Each lingual tonsils has a single crypts
MUCOSA--ASSOCIATED LYMPHOID
MUCOSA
TISSUE / MALT3
• Non capsulated
• Lymphoid nodules in
mucosa or submucosa of GI
tract respiratory tract
tract,
tract,
urinary tract.
Gut-Associated
Associated lymphoid
• Gut
tissue (GALT) Æ peyer’s
patches (B Cells surround
b T cells
by
ll & APCs)
APC )
• Bronchus-associated
lymphoid tissue (BALT) Æ
similar to peyer’s patches
Section of lung showing a collection of
lymphocytes in the connective tissue of
the bronchiolar mucosa, an example of
mucosa-associated
i d lymphoid
l
h id tissue
i
(MALT). Pararosaniline—toluidine 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
Graw-Hill
Hill , 2003. Pp 265 –
290.
Essentials of Human Histology, 2nd Edition, William J.
Krausse PhD
PhD, Little Brown & Company (Inc)
(Inc), 1996
1996. Pp
197-228
Color Textbook of Histologi, 2nd edition, Gartner LP, Hiatt
JL WB S
JL,
Saunders
d C
Company, Phil
Philadelphia,
d l hi Pennsylvania,
P
l i
2001. Pp 273-299
Consise Histology, 2nd edition, Don W Fawcett, Ronald P
Jensh, Arnold publisher, London, 2002. Pp 148-161