CHAPTER

W
a
3
Organs of Immune System
mmwunumummmu
3.1. INTRODUCTION
The immune
system consists of
classified functionally into two lymphoid organs (Fig. 3.1) and tissues which can
secondary (peripheral)
main
groups-primary be
(central) lymphoid organs
bursa of Fabricius lymphoid organs. Primary or central and
(in birds) and bone marrow (in
lymphoid organs are the thymus,
lymphocytes takes place. The lymph nodes, vertebrates) where maturation
(MALT) are the secondary or
peripheral
spleen, and
mucosal-associated lymphoid tissuesof
Iymphoid antigen and provide lymphoid organs. The secondary or
organs trap
lymphocytes to interactperipheral
antigen. sites for mature
with that
3.2. PRIMARY OR CENTRAL LYMPHOID
Immature ORGANS
developmentlymphocytes generated hematopoiesis, the
of blod cells,
mature and
in
specificity within the primary become process of
fornation and
and bone lymphoid organs, namely,committed to a
bursa ofparticular antigenic
marrow (in thy
mounting an immune mammals). A lymphocyte becomesthymus,
,
3.2.1.Thymus
response only after it matures within
immunocompet
a primary eFabricius
nt, i.e., ca(in birds)
lymphoide capable of
Thymus is greyish,
a
flat, bilobed lymphoid
the neck
on the front and
sites of organ situated abovee t
pharyngeal trachea. It
develops from the the heart
pouches and. on
lymphocytes named maturity, acts as the site epithelium and
of extending into
reaches peak thymus-derived lymphocytes
of
development andthird.and fourth
m
thymus beginsactivity
or
to
in childhood and T-lymphocytes
atrophy withoul any attains its largest size at T-celle The thymus
or
nO
apparent effect on puberty.
berty. Thereai
T-lymphocyte functio the
and is
 IMMUNE
SYSTEM 33
ORGANS OF
convenience, the average weight of the thymus is 70g
in
For
extremely sma small in old age. with weight of 3g in
age-dependent iinvolution leaves the thymus an average
and its very long-lived and can
fants due to the fact that T-lymphocytes are
probably
hfan
This is
age.
the old state for long periods of time.
irculate in the resting
ADENOIDS
TONSIL
LYMPH
NODES
THYMUS-
-SPLEEN
>PEYERS PATCHES
SMALL INTESTINE
ARGE
INTESTINE
APPENDIX
- BONE MARROW
TISSUE
LYMPHATICS
FiG. 3.1.
Lymphoid organs in human
body. The
Done marow, whereas the secondary orprimary or central lymphoid organs are the thymus anc
and mucosal associated lymphoid peripheral lymphoid organs are lymph nodes,
spleen
tissue (e.g., tonsils, Peyer's
and tissues are patch, etc.) The lyphoid
ymphatic vessels)interconnected with blood vessels
through which lymphocytes circulate.(not shown) and tissue
organ-
lymphatic
 IMMUNOLOGY AND
34 divided into0 a series oflo
series of iobules
and is
by a capsule irabeculae.
Each lobe of thymus
is
surrounded
other by strands of
connective
inner. The

tissue
called
outer component
is. Each
caller
from each
which are separated outer and is d
into two
compartments,
medulla (Fig.
The corter
3.2)
densely
obule is organized
whereas the inner
component
is called
is sparsely
populated with
thymocy
m"
cortex,
whereas the medulla in bone marrow.
thymocytes, are produced
packed with The latter Thym
Thymocytes develop
from
prothymocytes.
cortex of
the thymus,
and act as thymocytes.
ocytes
enter the Of the T-lympho hocytes produ
in
through only stream,
hymusblood T-lymphocytes.
5% leave the thymus as toviable
cortex and give
rise cells. Though the reason for this apnelones
dividerapidly in the cl
parent
eliminalion of T-lymphocyte
that it is the
believe
some
is not known,
wasteful process
that react against self.
NURSE CELL DIVIDING THYMOCYTE
CAPSULE
TRABECULA
DEAD THYMOCYTE
THYMOCYTE
CORTICAL EPITHELIAL CELL
MACROPHAGE
BLOOD
VESSEL
INTERDIGITATING DENDRITIC CELL
MEDULLARY EPITHELIAL CELL
HASSALL'S
CORPUSCULES
lobules separated
of a portion of the thymus showing several
FIG. 3.2. Cross section (diagrammatic) differentiated into outer cortex and
tissue strands); each lobule
by trabeculae (connective medulla is sparsely
inner medulla. Cortex is densely
populated by thymocytes, while
populated.
the thymus are criss-crossed by a three dimensional
Both the cortex and the medulla of the
dendritic cells, and macrophages, which make up
network consisting of epithelial cells,
and maturation of thymocytes. Some
framework of the organ and contribute to the growth
membrane extensions that surround as many
epithelial cells of the outer cortex possess long have
as 50 thymocytes. These cells are
called nurse cells. Other epithelial cells of the cortex
extensions that form a network and have been found to
long interconnecting cytoplasmic
interact with many of the thymocytes when they traverse the
cortex.
The function of the thymus is to generate T-lymphocytes and to confer immunological
educated in the
on to them during their stay in the organ. T-lymphocytes
so
competence
thymus become capable of mountingg cell-mediated immune response against appropriate
antigen. This is effected under the influence of the thymic microenvironment and several
hormones such as thymosin and thymopietin produced by the epithelial cells of the thymus.
The competent T-lymphocytes immediately move from thymus to the secondary or peripheral
lymphoid organs.
 SYSTEM
IMMUNE
ORGANSOF
3.2.2. Bone Marrow
the site of origin and development of B-lymphocytes or B-cells (bone
ne marrow is
and mice after birth.
Bon e
rrow derived lymphocytes) in mammals particularly in humans
the major sites of B-
fore birth, the yolk sac, foetal lever, and total bone marrow are
Before birth,
of
Bone marrow, therefore, is the mammalian equivalent of the bursa
lumphocyte maturation.
ymph
Fabricius in birds.
differentiation of lymphoid
Development of B-1ymphocytes (B-cells) begins with the within
etem cells
into the earliest distinctive progenitor B cells (pro-B cell), which proliferate
in the shaft of a
he hone marrow filling the Extravascular spaces between large sinusoids
ne. Proliferation and differentiation of pro-B cells into precursor B cells (pre-B cells)
the bone marrow stromal cells. The stromal cells
auires the microenvironment provided by
and (2) secrete
ithin the bone marrow : (1) interact directly with the pro-B and pre-B cells
that are required fordevelopment.
various cytokines
is not the site of origin and development of B-lymphocytes (B-cells) in all
Bone marrow
wherein the
mammals. In cattle and sheep, the foetal spleen is the primary 1ymphoid tissue
maturation, proliferation, and diversification of B-cells take place during early gestation.
huring later gestation this function is performed by ideal Peyer's patch, a patch of tissue
nbedded in the wall of the intestine. In rabbit, gut-associated tissues (e.g., appendix) act as
Drimary lymphoid tissue for mathiration, proliferation, and diversification of B-cells.
3.2.3. Bursa of Fabricius
Bursa of Fabricius is a primary lymphoid organ in birds where stem cells from yolk sac,
foetal lever, and bone marrow mature, proliferate, and differentiate into bursa-derived
lymphocytes called B-lymphocytes or B-cells. Bursa of Fabricius arises as a pouch from the
dorsal part of cloaca (fluid gut) in birds, Bursa of Fabricius is sensitive to hormones; admin-
istration of testosterone at the early embryostage completely prevents its formation (hormonal
bursectomy). Surgical removal of bursa (bursectomy) from newly hatched chickens destroys
their subsequent ability to produce antibodies. The B-cells mature, proliferate, and differenti-
ate into bursa and then migrate from it and reach outer or superficial cortex of the germinal
follicles and medullary cords of peripheral lymph nodes and lymphoid follicles of spleen
where, following appropriate antigenic stimulation, transform into plasma ells and secrete
antibodies. Like thymus, the bursa of Fabricius starts to shrink or atrophy at puberty.
3.3. SECONDARY OR PERIPHERAL LYMPHOID ORGANSS
As stated earlier, the lymphocytes mature, proliferate, and differentiate in the primary or
central lymphoid organs. These lymphocytes migrate therefrom via circulation to the
secondary or peripheral lymphoid organs. Here they bind appropriate antigens and undergo
in the secondary lymphoid organs, the
further antigen-dependent differentiation. Once
lymphocytes do not remain there but move from one lymphoid organ to another through the
blood and lymphatics. The passage of lymphocytes facilitates the induction of an immune
response. Lymph nodes and the spleen are the most highly organized secondary or peripheral
lymphoid organs, whereas mucosa-associated lymphoid tissue (MALT) is the less organized
lymphoid tissue.
 IMMUNOLOGY AND MEDICAL MICROBIO. LOGY
36
ORGANS
3.3.1.LymphNodes structures
clustered at junctions of L
3.3.2.
encapsulated, bean-shaped contain a reticuia
ymph nodes are small, throughout the body.
Lymph nodes The sp
ymphatic vessels which are distributed dendritic cells, and
tilter out pathogeni encaps
macrophages and a lymph for trap
network packed with lymphocytes, lymph percolates through
As the
and antigens from the Iymph. is trapped by the phagocyti encaps
Organisms the lymph
that is brought in with resulti
node, any pathogen or antigen tissue
cells and dendritic cells. and the medulla
the cortex, the paracortex, (Fig.
A lymph node consists of three regions aggregates of
3.3). Cortex is the outermost region and contains several roundedcells
(Fig. dendritic
follicular arranged in
macrophages. and
ymphocytes (mostly B-lymphocytes), centre surroundedby small dark-
has a pale-staining germinal
primary follicles. Each follicle beneath the cortex is the paracortex. It is the
staininglymphocytes. The deeper region lying large number of T-
medulla. Paracortex possesses
Zone between the cortex and the to have migrated from
dendritic cells thought
ymphocytes and also contains interdigitating number of T-lymphocytes in it,
node. Because of the presence
of large
tissues to the lymph area incontrast to the cortex which is
is also referred to as a thymus-dependent
the paracortex
the inner most region lymph of node, Is more sparsely
a thymus-independent area. Medulla, cells present, many are
cells. Of the lymphoid -lineage
populated with lymphoid-lineage
molecules.
plasma cells actively secreting antibody
AFFERENT LYMPHATIC
VESSEL
i
B-LYMPHOCYTES
1
cORTEX
o
- PARACORTEX
GERMINAL
CENTRE
MEDULLA
EFFERENT LYMPHATIC
VESSEL
node structure showing cortex, paracortex, medulla, afferent and efferent lymphatic
FIG. 3.3. Lymph
vessels, and lymphocytes
which
Each lymph node has a number of lymph vessels called afferent lymphatic vessels,
of a lymph node at numerous sites and empty lymph into the sub-capsular
pierce the capsule
sinus. The lymph
now percolates slowly inward through the cortex, paracortex, and medull
and antigens carried by
a, allowing phagocytic cells and dendritic cells to trap pathogens
then is drained into a single large 1lymph vessel called efferent
the lymph. The lymph into a large vein in
which empties
lymphatic vessel that carries the lymph to the thoracic duct,
the neck.
 o
ov oi
vo id
d
SYSTEM an
adults,
is
IMMUNE
in p l e e n i s s p e c i a l i z e d

OF
s p e c i a l i z e a

weight is
in
g8 in
ORGANS Spleen
and 200 Sple and
being
inches long lymphoid
d
organ.
cavity
3 . 3 . 2 .S p l e e n

about 5 peripheral
a b d o m i n a l
interior

is p eripheral
left the
T h es p l e e n , whic. hich secondary
s e c o n d a r y
or
or high in the into of
largest present
trabeculae,
types
the
the is called two

apsulated,
and
encapsulated,and antigens
and
of
projections,
are
filled by zone

b l o o d - b o r m e
number
c o m p a r t m e n t s marginal
f o rt r a p p i n g b l o o d
a diffuse of
extends
These
fortrapping a number
capsule by
its by large
c o m p a r t m e n t s .

separated
ncapsulated,
of which
are
populated
formation

resultingiin the
nthe. pulp, sinusoids

and
white
of
resulting network

red pulp consists

of a
tissues, the red pulp
The
34).
(Fig.
3.4).Th

Eie,
- GASTRIC SURFACE

RENALSURFACE HILUM

SPLENIC ARTERY

SPLENIC VEIN-

A
CAPSULE

LYMPHOCYTES

TRABECULA

PRIMARY
FOLLICLE
VASCULARA MARGINAL
WHITE PULP
SINUSOID ZONE
PERIARTERIOLAR
LYMPHOID
SHEATH (PALS)
GERMINAL

CENTRE

GERMINAL CENTER
RED PULP
SPLENIC
SPLENIC ARTERY
VEIN

B
which is the largest secondary
FIG. 3.4. Structure of spleen. (A) Morphological view of spleen, section
in adults, and (B) diagrammatic cross
lymphoid organ being about 5 inches long
showing different internal components of the spleen.
38 IMMUNOLOGY AND MEDICAL MICROBIOLOC

In tact, red pulp is the

erythrocytes (red blood cells) and macrophages and few lymphocyes.
and eliminated. The white puln
egion where old and defective erythrocytes are destroyed
consist of the branches of the splenic artery that make a periarleriolar lymphoid
sheath (PALS) populated heavily by T-lymphocytes. Periarteriolar lymphoid sheath
(PALS) is attached with primary lymphoid follicles that are rich in B-lymphocytes. The
marginal zone separating the red pulp from white pulp is populated by ymphocytes and

macrophages.
When the blood-bome antigens enter the spleen the B- and 1-lymphocytes present in
periarteriolar lymphoid sheath (PALS) are initially activated. Here interdigitating dendritic
cells capture antigen and present it combined with class ll MHC molecules (major
histocomputibility molecules) to Th cells (T helper cells). Once activated, these TH cells can
then activate B-lymphocytes (B-cells). The activated B-lymphocytes, together with some T.
cells then migrate to primary follicles in the marginal zone. When the primary follicles are
Chalienged by antigen, they differentiate into characteristic secondary follicles. The latter
contain germinal centres (similar to those occuring in lymph nodes) where rapidly dividing
B-lymphocytes and plasma cells are surrounded by dense clusters of concentrically arranged

lymphocytes.
3.3.3. Mucosal-associated Lymphoid Tissue (MALT)
The mucous membranes lining the alimentary, respiratory, and genitourinary systems have a
very large combined surface area (about 400 m-; nearly the size of a basketball court), which
IS constantly exposed to numerous antigens and is the major site of entry for most pathogens.
These vuinerable membrane surfaces possess a group of organized lymphoid tissues which
defend it from pathogens and antigens. The group of organized lymphoid tissues is known
collectively as mucosal-associated lymphoid tissue (MALT). Thereare several types of
MALT: the most studied one is the gut-associated lymphoid tissue (GALT) which includes
tonsils, Peyer's patch, appendix, and loosely organised clusters of lymphoid cells in the
lamina propria of intestinal villi. Mucosal-associated lymphoid tissue (MALT) is functionally
very significant in immune system of the body because of the presence of large number of
antibody-producing plasma cels in it. The number of plasma cells in MALT far exceeds that
of the total of the number of plasma cells present in spleen, lymph nodes, and bone marrow

3.3.3.1. Tonsils
There are three groups of tonsil present at three different locations: palatine, lingual, and
pharyngeal (adenoids). Palatine group of tonsil occur at the sides of the back of the mouth;
lingual in the basal region of the tongue; and pharyngeal (adenoids) in the roof of the
nasopharynx (Fig. 3.5) All the aforesaid tonsil groups are nodule-like and consist of a
meshwork of reticular cells and fibres interspersed with
lymphocytes, macrophages,
granulocytes, and mast cells. The
B-lymphocyles are organised into follicles and germinal
centres. The germinal centres are surrounded
by regions showing T-lymphocyte activity.
However, the tonsils protect against antigens that enter
routes.
through the nausal and oral epithelial
 39
ORGANS OFIMMUNE SYSTEM
LINGUAL
TONSILS

PALATINE
TONSIL

PHARYNGEAL
TONSIL (ADENOID)

NOSE
TONGUE
TEETH
FIG. 3.5. Three types of tonsils: palatine, lingual, and pharyngeal (adenoid).

3.3.3.2. Peyer's Patch

under
in the submucosal layer present beneath the lamina propria lying
Peyer's patches occur
30-40 lymphoid
intestinal villi. Each Peyer's patch is a nodule of
the epithelial layer of
Like lymphoid follicles in other sites, those that compose Peyer's patches
can
follicles.
develop into secondary follicles with germinal centres (Fig. 3.6).
INDUCTIVE SITE VILLI

INTESTINAL LUMEN

DIFFUSE
FOLLICLE

LAMINA PROPRIA
PRIMARY
FOLLICLE
SUBMUCOSA GERMINAL
CENTER
MUSCLE
LAYER

PEYER'S PATCH

FIG. 3.6. Cross sectional view of the mucous membrane lining the intestinal lumen, and showing
of follicles
Peyer's patch and lamina propria. Peyer's patch is constituted by nodule lymphoid
in submucosa, whereas lamina propria contains loose clusters of lymphoid cells and diffuse
follicles.

3.3.3.3. Lamina propria

Lamina propria occurs under the epithelial layer of intestinal villi (Fig. 3.6.). It is populated
with large number of plasma cells,macrophages, activated T helper cells (activated TH cells)
40 MICROBIOLOGy
IMMUNOLOGY AND MEDICAL

in loose clusters. More than

15000 lymphoid follicles have been reported within the lamina
propria of
healthy eh
propria a healthy child.

Questions
1. do you understand
by primary and secondary lymphoid organs ? List tne primary
ymphoid organs and summarize their functions in immune response.
2. and Summarize
are peripheral lymphoid organs ? List the
their functions in the immune
peripheral lymphoid organs
response.
3. Give the diagram of () a human body well-labelled with lymphoid organs, (i) cross section
owing ditferent parts of the thymus, and (i)
spleen.
cross section showing diferent parts of the

4. Write short notes on () nurse

cells, (i) bursa of Fabricius, (i) bone marroW, (V) mucosa
associated lymphoid tissue (MALT), (V)
Peyer's patch, (vi) lymph node.