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Lymphoid tissue and lymphoid organs
The lymphatic system is specialized form of connective tissue that
consists of group of cells, tissues and organs.
 It monitors the body surface and internal fluid
compartments and reacts to the presence of
potentially harmful antigens included in this
system: thymus, spleen, lymph nodes,
lymphatic nodules and diffuse lymphatic
tissue.
 The lymphatic tissue & organs are collectively referred
as the immune system including the lymphoid cells
present throughout the circulation.
What is lymph = lymph is a transudate from the blood
containing crystalloid materials containing same protein of plasma.
Suspended in the lymph are the chief cellular components of the
lymphatic tissues, lymphocytes they circulates within the lymphatic
vessels, scattered along the lymph vessels are numerous small
bean-shaped structure called lymph nodes.
 Lymph nodes act as fibers removing
bacteria and other particulate.
 Lymph node adds lymphocytes to
the lymph.
Introduction
The bone marrow is the predominant source of stem cells
(hemocytoblasts) from which lymphoid cells are derived (And
persistence to adult life).
In late fetal life many stem cells migrate from the bone marrow to
the primary lymphoid organs.
In the primary lymphoid organs. These immigrant stem cells
proliferate & differentiate into immunocompetent cells. These cell
are processed
i.e. become competent to recognize and destroy invading
microbes and have ability to distinguish between self and nonself
molecules.
After processing lymphocytes (both T & B) transported by the
cardiovascular system to the secondary lymphoid organ.
The primary or central lymphoid organs
1-Thymus
2- Gut associated lymphoid tissue e.g. (Appendix & pyre’s
patches) (Correspond to bursa of fabricius in bird).
3- The liver or bone marrow it self depending on the species
or the stage of development or both.
T Lymphocytes mature in the thymus and so-called thymus
derived cells (T lymphocytes), which are involved in cellmediated (cellular immunity).
B lymphocytes (bursa- derived cells) mature in the bone marrow
or gut associated lymphoid tissue are involved in humoral
immunity and the production of proteins antibodies.
These T & B lymphocytes are called virgin cells (before exposure
to antigen).
Secondary lymphatic organ (peripheral)
These include lymph nodes, lymphatic nodules, spleen & tonsils.
In these organs T & B lymphocytes undergo antigen dependent
proliferation and differentiation into effectors lymphocytes and
memory cells.
Immunological tolerance = when immune system can recognize
self antigen but doesn’t attempt to attack them.
 Clinical note
Autoimmune system: involve malfunction of immune system
i.e. loss of immunological tolerance, e.g. Grave’s disease
thyrotoxicosis antibodies against receptors of TSH in thyroid
follicles.
Types of immunity
In cell mediated immunity activated T lymphocytes (effectors T
cells) attaching the antigen either directly or by releasing
lymphokines.
Many types of lymphokines e.g.
1- Lymphotoxin = kill the antigen or lysis of antigen.
2- Blastogenic factor induce proliferation of non sensitized
lymphocytes.
3- Chemotaxis = attract macrophages and different types of
leukocytes which assist lymphocytes in eliminating the
antigen.
4- Interferon (kill cancer cells) see page 222 table.
o Cellular immunity characterized by localized reaction
because the lymphocytes seak out the antigen or risk after
the antigen.e.g. tuberculin test and histoincompatible
(rejection of transplant).
o Also it is usually a slow or delayed hypersensitivity
reaction.
There are many types of effector T cells:
 T cell recognize & destroy tumor cell
 T lymphocyte recognize & fight organism that
produce infection.
 T lymphocytes which regulate immune or
allergic response, it secrete interleukin.
 Helper T lymphocyte = it enhance the immune
response recognize the antigen and attract
macrophages or B cells to attract antigen.
 T cells which only attract the antigen &
concentrated.
 T cells which suppress the immune response
or inhibit it, T suppressor cells (inhibit
attaching self antigen). These can be
recognized by unique surface e.g cecule
(specific receptors).
 Memory cells = they don’t responed to initial
primary response to an antigen, but they
increase the circulating population of pre
programmed lymphocytes capable of
recognition of a particular antigen and
responding to a second exposure.
In humoral immunity:
Activated B lymphocytes and plasma cells secrete specific
antibodies that circulate, combine with antigen and form
inactive complexes.
Here not the cells seek out the antigen but instead their
secretory products (antibodies) distributed throughout the
body fluid and seek out or running after the antigen.
The secondary response is usually very rapid and intense
and may cause anaphylactic shock such as penicillin, insect
venous..
Antibodies are proteins found in the plasma and referred to
them as immunoglobulins:
- Against bacteria
Or - against bacterial toxin like tetanus
There are 106 – 109 different types of AB in one person.
There are five different classes:
1. Ig M:
High molecular weight = macroglobulin.
 It is important in primary response.
 It is a cytolytic agent (i.e lyses of foreign cells).
 It plays important role in antigen agglutination and
opsonization.
 Activate complement.
2. Ig G:
o
o
o
o
o
It is predominant in the serum.
Neutralize bacterial toxins and viruses.
Important in secondary response.
Not activating complement.
Cross placenta, so give passive immunity to the fetus
and secreted in milk.
3. Ig A:
Two types: Serum Ig A and dimeric form found in seromucous
secretion so called secretory Ig A or s Ig A .
It is stabilize against proteolytic enzyme by combining with
other protein (J protein) protect the body surfaces from
invading of organism. Help esinophils to recognize & kill
parasite.
4. Ig E:
Play important role in allergy and parasitic infection.
It binds to mast cell and basophile to release histamine
and heparin, help esinophil to recognize & kill parasite.
Its level is very low in the serum.
5. Ig D
 It is responsible for lymphocyte activation.
 It is usually found in the surface of B & T lymphocytes to
activate B cells to differentiate into plasma cell with Ig M.
AIDS = virus HIV. binds to C D4 molecule of T helper cell
Thymus
It develops from the third branchial arch and migrates
caudally.
It is a bilobed organ.
It is well developed from the time of birth to puberty.
It is situated in the midline of the superior
mediastinum.
i.e. behind the manubrium sterni.
It is usually not seen in cadavers because it undergo
rapid autolysis.
It consists of : Stroma and parenchyma
Stroma = Capsule & framework.
 The thymus surrounded by C.T capsule, septa extend from
the capsule to the thymic tissue and divide the thymus into
lobules (they are not true lobule). Smaller septa extend
into each lobule from main septa.
 Reticular fibers and cells are absent but instead.
There are epithelioreticular cells which are attached to
each other by desmosomes and form the framework of
the thymus.
 They are not phagocytic as reticular cells of other lymphoid
organ.
 They are secretory cells produce hormones like substance
which regulate T cell development.
 They are endodermal in origin.
Parenchyma
Each lobule is separated into:
a- A peripheral cortex.
b- And a central medulla
Because the lobules they are not complete (not true lobule)
the medulla become continuous with adjacent lobules. May be in
some section the lobule is completely surrounded by cortex and
the medulla present exactly in the center and this give confusion
with lymphatic nodule with germinal center.
The cortex is intensely basophilic due to the presence of small
numerous:
(1) Lymphocytes, lymphocytes have intensely stained
nuclei, (thymocytes).
(2) Numerous macrophages which can be displayed with
PAS reaction. They are present to phagocyte or destroy
lymphocytes which randomly programmed against self
antigen.
(3) Epithelial reticular cellular abundant:
Type I, Type II, Type III
The medulla = Stained less intensely than the cortex because,
like germinal center of lymphatic nodules, it contains mostly large
lymphocytes with paler staining nuclei and with relatively more
cytoplasm than in small lymphocyte (fewer).
 Also they contain epithelioreticular cells with euchromatic
nuclei.
 Few mast cells, macrophage, plasma cells, granular
leukocytes may be found in small numbers.
Thymic corpuscles = Hassels corpuscles = unknown function.
 They are distinction feature of thymic medulla.
 They are isolated masses of closely packed, concentrically
arranged epithelioreticular cells, mainly type VI, these cells
stain bright pink in H & E).
 The center is formed of epithelial cells undergo
degeneration + may be calcification
“keratinized center is look like pink stained hyaline
Blood – thymic barrier
The blood vessels pass from the capsule to penetrate and ramify
the interlobular C.T. They enter the parenchyma by coursing along
the corticomedullary zone.
The arteries extend into the cortex and from a capillary network
that extensively anastomose with one another.
o Subsequently the capillaries drain into the pot capillary
venules and veins on the medulla.
o Antigens that penetrate to medulla are rapidly phagocytoced
by macrophages before they can diffuse to the cortex.
o In the cortex the capillaries are ensheathed by epithelioreticular cells and a basal lamina is interposed between the
epithelioreticular cells and perivascular connective tissue.
All these components form the blood thymic barrier:

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Capillary endothelium.
Endothelial basal lamina
Perivascular C.T containing many macrophages.
Basal lamina of epithelioreticular cell.
Epithelioreticular cell sheath.
Thymic Function
 During fetal life and childhood, the thymus is the site of
programming, differentiation and proliferation of T
lymphocytes.
 These processes are enhanced by hormone like factors,
which produce by epithelioreticular cells. These factor
enhance the transformation of bone marrow stem cells
(pre-T cells into mature T cells, e.g. serum thymus factor,
thymopoietin, thymosin, thymulin.
 The cortex of thymus show extensive proliferation
activity of lymphocytes that undergo blastogenesis.
This process don’t involve antigen stimulation in neonate.
So, thymus is important in the immunological maturation of T
lymphocytes.
Thymoctomy in neonatal animals showed that the animals
are unable to produce immunocompetent T cells and send it to
peripheral lymphoid tissue, therefore these animals are
susceptible to infection.
At puberty thymus undergo involusion and replaced by adipose
tissue. This because the immunocompetent T cells has been
established (long life).
Accidental involutions of the thymus occur as a result of sever:
(1) Stress, (2) prolonged disease, ionizing radiation and
(3) deficiencies.
1, 2, & 3 reversed if the cause is removing.
 Enlargment of thymus after puberty associated with or
disease called Mysthenia gravis.
 Some hormones influence T cell maturation e.g.
adrenocorticosteroid – thyroxyne & somatotropin (GH).
 Congenital failure of the thymus to develop is called
Digeorg’s syndrome. The patients can not produce T
lymphocytes and usually die at young age from infection.
They also lack parathyroid glands and die from
tetany.
The Bursa Equivalent = Bursa of fabricius
BF: It is the avian central lymphoid organ that generates B
lymphocytes.
The bursectomized chick do not develop the capacity to
produce humoral antibodies.
 In mammals, an equivalent developmental system exists,
possibly in the gut – associated lymphoid tissue.
 A gammaglobulinemia, in which no humoral immunity
develop. Neonate are succeptibal to bacterial infection
sever infection such as encephalitis + meningitis.
Peripheral (secondary) lymphoid organ
The spleen
 It is the largest lymphatic organ. It is located in the upper
left quadrant of the abdomen.
 The stroma
 It is covered externally by peritoneum (serous coat)
exceptant the hilum.
 Then its encapsulated by dense, irregular C.T (capsule).
 Thin trabeculae extend into the parenchyma from
the capsule. Trabecula also branched within the
parenchyma of the organ.
 Capsule + branching trabeculae consist of elastic
fiber and smooth muscle.
 In some mammals myofibroblasts contract to
discharge stored red blood cells in the circulation
because these species have the ability to hold large
volume of RBCs in the spleen.
 The stroma also contain reticular fibers + reticular
cells which form a framwork around the parenchyma
of the organ.
The parenchyma
 The substance of the spleen consists of splenic pulp.
 This is divided into white and red pulp, based on the
color seen in fresh state.
 The white pulp is islands on a sea of red pulp.
The white pulp = (Note: central only in the peripheral venul
center.)
Malpigian corpuscles
The area where PALS formed, there is no nodular appear.
They appear as basophilic area in H&E due to present of a
numerous lymphocytes those posses heterochromatic nuclei.
It is composed of aggregation of lymphoid tissue around the
central arterioles forming corpusles.
Splenic artery traverse the capsule and branched in the trabeculae
and then enter the white pulp, here the artery is called central
artery (euentris fistion).
o In some artery, around the central artery there is
aggregation of lymphocytes which constitute the
periarterial lymphatic sheath (PALS). It has cylindrical
configuration around the central artery.
o The PALS is differentiated from the lymphatic nodule by
the presence of the central artery. True lymphatic nodules
do occur. They appear as localized expansion of PALS and
tend to display the center artery to the side (eccentric in
position) rather than a central position.
Not be confused with lymphatic nodule which has similar
appearance and the center in both may be called germinal
center.
PALS T lymphocytes may be consider similar to the thymic
dependent zone (of lymph node)
The germinal center of the lymphatic nodule of the white pulb
mainly contains B lymphocytes.
T lymphocytes present toward the periphery at the junction of
WP with RP. (marginal zone).
The red pulp
The parenchyma of the red pulp is composed of diffuse
lymphoid tissue organized in cords which is highly infiltrated
with blood cells mainly RBC. They are (cords) surrounded by
splenic venous sinuses.
Therefore the red pulp consists mainly of splenic sinuses
separated by splenic cords (cords of Biliroth).
The splenic cords mainly consists of reticular cells network
and reticular fibers. This network or mestwork contains large
number of RBC, macrophages, lymphocytes, plasma cells and
granulocytes. Macrophages destroyed the old RBC. The
venous sinuses lined by phagocytic reticular cells.
Blood supply
Capsular
trabecular
central artery within the
white pulp. Then it terminate in the red pulp as highly
branched small vessels termed penicillin, each penicillin
showed a localized thickening of its wall that is called
ellipsoid.
Blood from the splenic cord drain into the splenic sinuses
drained into red pulp veins. They are present in between the
splenic cords and have discontinues wall – red pulp vein join
the trabecular vein
splenic vein.
The circulation in the splenic is open because capillary open
into the veins – venous sinuses are lined by reticular cells
resemble macrophages not endothelium.
o Marginal zone, red pulp cord (splenic cord)
trap
antigen and old blood cells. i.e. red pulp = blood
filtration from macromolecule, antigen, senile cells.
o Germinal center is involved in humoral immunity.
Antigen trap by macrophages of marginal zone + splenic cord
stimulate B cells toMarginal zone, red pulp cord
(splenic cord) lead to trap antigen and old blood
cells. i.e. red pulp = blood filtration from
macromolecule, antigen, senile cells.
o Germinal centers are involved in humoral immunity.
Antigen trap by macrophages of marginal zone + splenic cord
stimulate B cell to proliferate produce antibodies lead to attack
antigen.
o Role in cell –mediators immunity not clear.
o Reservoir for blood – born elements such as lipid,
irons, plasma protein.
o Destruction of RBC.
Accessory spleen at the hilum or tail of pancreas in 16% of cases.
The lymph node
They are small encapsulated organs located along the pathway of
lymphatic vessels. This association reflect their function as lymph
filters.
Stroma
The supporting tissue of lymph nodes are:
1. Capsule: lymph node is covered by a dense C.T capsule.
2. Trabeculae: extend from the capsule forward the substance
of the node.
3. Reticular fibers or tissue = composed of reticular cells and
reticular fibers that form of fine supporting meshwork
throughout the remainder of the organ.
Two types of lymphatic vessels serve the nodes:
Afferent lymphatic vessels
Convey lymph toward the node and enter at various points
on the convex surface of the capsule.
Efferent lymphatic vessels = convey lymph way from the node and
leave at the hilum (concave surface).
o In between there is a system of sinuses along the capsule
(marginal sinuses) and medullary sinuses in between
medullary cards. Both will drain into efferent lymphatic
vessels.
The parenchyma
The parenchyma of the lymph node is divided into cortex and
medulla.
 The cortex is formed the outer portion of the node except at
the hilum.
 It is composed of: (1) nodules with distinct germinal centers.
 The cortex adjacent to the medulla is free of nodules and is
formed of : (2) diffuse lymphoid tissue, this area is called
paracortical or juxtamedullary cortex or deep cortex. Also
called thymus-dependent cortex.
Note:
Thymectomy of neonate
underdevelopment of this zone.
The medulla
Is the inner part of the node (medullary cords)
 It consists of cords of lymphatic tissue (medullary cords)
separated by lymphatic sinuses called medullary sinuses.
 Reticular fibers are present in the medullary cords crosssupportive elements. B lymphocytes mainly, plasma cells,
macrophages are present in the cords.
Distribution of B + T lymphocytes.
 B lymphocytes are most common in the cortex
(germinal center) and medullary cords.
 T lymphocytes are common in the deep cortex or para
cortex.
 Both T & B lymphocytes are present where the deep +
nodular cortex meet.
Note
Cell mediated immunity (e.g. viral. Chronic TB, skin transplant)
stimulate proliferation of T lymphocytes in the diffuse cortex.
Humoral immunity (acute bacterial infection) stimulates
proliferation of B lymphocytes in the nodular cortex (enlargement
of the germinal centers).
Function of the lymph nodes
The lymph born antigen originate from the connective tissue
regions of the body are transported by afferent lymphatic
vessels to the regional lymph nodes.
These antigen will be phagocytized by macrophages and
follicular dendritic cells.
These are present in the lymphatic nodule.
They preserve the antigen on their plasma membranes.
The antigen is exposed, thus, they are presented to
immunocompetent memory B cells.
Recognition of an antigen by a B cell may necessitate the
involvement of helper T cell to facilitate activation of B cell.
Activated B cell
a. Migrate to the germinal center.
b. Undergo mitotic divisions.
c. Give rise immature immunoblast that proliferate and
give rise to plasma cells and memory B cells.
Plasma cells migrate to the medullary cords where they synthesize
and release specific antibodies into lymph
blood
memory B cell circulates to different region and in secondary
exposure to the antigen proliferate
plasma cells
antibodies.
Enlargement of the lymph node is due to proliferation of B
lymphocytes and enlargement of the germinal centers.
Gut associated lymphoid tissue
 These organs (either whole organ or part) represent the
bursa equivalent in human and some mammals.
 These include = tonsils, pyers patches, the appendix, the
solitary nodules that scattered throughout the GIT tract
numerous in the colon.
In GIT + respiratory tract, the lamina propria contain large
number of lymphoid cells and often considered as a lymphoid
tissue. Plasma cells here (in this layer) secret secretory IgA to
prevent bacteria and viruses to penetrate overlying epithelium.
When there is highly organized lymphoid tissue (such as previously
mentioned) it is become greatly enlarged.
The tonsils
There are three distinct tonsils. They are forming incomplete
ring at the entrance of the or pharynx..
These are
palatine (paired)
Lingual (paired)
Pharyngeal (diffuse lymphatic tissue)
(single).
 The palatine tonsil and lingual tonsil are covered
with stratified squamous epithelium.
 Pharyngeal tonsils is covered by pseudostratified
columnar ciliated epithelium with goblet cells
(nasopharynx)
 The epithelium of palatine + lingual tonsil
underneath skeletal muscle + lingual glands is
thrown into folds forming crypts (usually deep),
which may bifurcate underneath the epithelium the
lymphoid tissue arrange in single layer of lymphatic
nodules with germinal centers. The nodules are a
symmetrical (unlike lymph node cortex)
 The covering epithelium is called usually follicular
epithelium that contains macrophages, lymphocytes,
plasma cells and polymorph nuclear cells.
Peyer’s Patches
The lymphatic nodules are present in solitary form in the lamina
propria and submucous of the small intestines.
Aggregation of these lymphatic nodules in the ileum is called
peyer’s patches.
These aggregations (30 – 40 in number) are usually confined to
the lamina propria and may extend into the submucosa.
The follicular epithelium associated with the nodules is highly
specialized. These are areas where no villus projections occur.
While most of the constitute are typical columnar with microvilli.
Some are attenuated cells actively traps antigen and present them
to the lymphoid organ below.
Palatine Tonsil
Pharyngeal tonsil