Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
The immune system and lymphoid system
The body has a system of cells—the immune system—that has the ability to
distinguish "self" (the organism's own molecules) from "nonself" (foreign substances).
This system has the ability to neutralize or inactivate foreign molecules (such as
soluble molecules as well as molecules present in viruses, bacteria, and parasites) and
to destroy microorganisms or other cells (such as virus-infected cells, cells of
transplanted organs, and cancer cells). On occasion, the immune system of an
individual reacts against its own normal body tissues or molecules, causing
autoimmune diseases.
Antigens
A molecule that is recognized by cells of the immune system is called an antigen and
may elicit a response from these cells. Antigens may consist of soluble molecules
(such as proteins, polysaccharides, and nucleoproteins) or molecules belonging to
whole cells (bacteria, protozoa, tumor cells, or virus-infected cells). The cells of the
immune system do not recognize and react to the whole antigen molecule but instead
react to small molecular domains of the antigen known as antigenic determinants or
epitopes. The response of the organism to antigens may be called cellular (in which
lymphocytes are primarily in charge of eliminating the antigen) or humoral (in which
molecules secreted by plasma cells, called antibodies, are primarily responsible for the
response). Some epitopes (e.g., polysaccharides of bacterial walls or lipids) usually
elicit a humoral response whereas proteins elicit both a cellular and humoral response.
More details on cellular and humoral immune responses are provided below.
Antibodies
An antibody is a glycoprotein that interacts specifically with an antigenic
determinant. Antibodies belong to the immunoglobulin (Ig) protein family. Free
molecules of antibodies are secreted by plasma cells that arise by proliferation and
terminal differentiation of clones of B lymphocytes whose receptors recognize and
bind specific epitopes. These secreted antibodies either circulate in the plasma and
may leave the blood vessels reaching the tissues or are present in the secretion of
some epithelia (e.g., of the mammary gland and salivary glands). Other antibodies are
not free molecules, but are integral membrane proteins of the surface of lymphocytes.
In any case, each antibody combines with the epitope that it specifically recognizes.
There are several classes of antibody molecules but all have a common design:
they consist of two identical light chains and two identical heavy chains bound by
disulfide bonds and noncovalent forces. The isolated carboxyl-terminal portion of the
heavy chain molecules is called the Fc region(Figure ,1). The Fc regions of some
1
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
immunoglobulins are recognized by receptors present on the membrane of several
cell types and for this reason antibodies may bind to the surface of these cells. The
first 110 amino acids near the amino-terminal part of the light and heavy chains are
very variable among different antibody molecules. Therefore, this region of the
molecule is called the variable region. The antigen-binding site of an antibody
consists of the variable regions of one heavy and one light chain. Thus, each antibody
molecule has two binding sites for antigens, both for the same antigen. The molecules
of some of the immunoglobulin classes may form dimers, trimers, or pentamers.
(Figure ,1) Basic structure of an immunoglobulin (antibody).
Two light chains and two heavy chains form an antibody molecule. The chains are linked by
disulfide bonds. The variable portions near the NH2 end of the light and heavy chains bind the
antigen. The Fc region of the molecule may bind to surface receptors of several cell types.
Classes of Antibodies
The main classes of immunoglobulins in humans are immunoglobulin G (IgG), IgA,
IgM, IgE, and IgD (Table 14–1).
Table 14–1. Summary of Classes of Antibodies.
lgG
lgM
lgA
2
lgD
lgE
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
Structure
Monomer
Pentamer
Dimer or Monomer
trimer
with
secretory
component
Monomer
Antibody
percentage
the serum
80%
5–10%
10–15%
0.002%
0.2%
in
Presence in sites
other than blood,
connective
tissue,
and
lymphoid organs
Fetal
B
circulation in lymphocyte
pregnant
surface (as a
women
monomer)
Secretions Surface of B
(saliva,
lymphocytes
milk,
tears, etc)
Bound to
the surface
of
mast
cells and
basophils
Known
functions
Activates
phagocytosis,
neutralizes
antigens,
protects
newborn
Protects
the
surfaces of
mucosas
Participates
in allergy
and
destruction
of parasitic
worms
First
antibodies to
be produced
in an initial
immune
response;
activates
complement
Functions as
a receptor to
antigens
triggering
initial B cell
activation
IgG is the most abundant class representing 75% of serum immunoglobulins. It is
produced in large amounts during immune responses. IgG is the only
immunoglobulin that crosses the placental barrier and is transported to the circulatory
system of the fetus, protecting the newborn against infections for a certain period of
time.
IgA is the main immunoglobulin found in secretions, such as nasal, bronchial,
intestinal, and prostatic, as well as in tears, colostrum, saliva, and vaginal fluid. It is
present in secretions as a dimer or trimer called secretory IgA, composed of two or
three molecules of monomeric IgA united by a polypeptide chain called protein J and
combined with another protein, the secretory, or transport, component. Because it is
resistant to several enzymes, secretory IgA subsists in the secretions where it
provides protection against the proliferation of microorganisms. IgA monomers and
protein J are secreted by plasma cells in the lamina propria of the epithelium of the
digestive, respiratory, and urinary passages; the secretory component is synthesized
by the mucosal epithelial cells and is added to the IgA polymer as it is transported
through the epithelial cells.
3
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
IgM constitutes about 10% of blood immunoglobulins and usually exists as a
pentamer. Together with IgD, it is the major immunoglobulin found on the surface of
B lymphocytes. These two classes of immunoglobulins have both membrane-bound
and circulating forms. IgM bound to the membrane of a B lymphocyte functions as its
specific receptor for antigens. The result of this interaction is the proliferation and
further differentiation of B lymphocytes into antibody-secreting plasma cells.
Secreted IgM, when bound to antigen, is very effective in activating the complement
system.
IgE usually exists as a monomer. As its Fc region has a great affinity for receptors
present on the surfaces of mast cells and basophils, it attaches to these cells after
being secreted by plasma cells and only small amounts are found in the blood. When
IgE molecules present on the surface of mast cells or basophils encounter the antigen
that elicited the production of this specific IgE, the antigen–antibody complex
triggers the liberation of several biologically active substances, such as histamine,
heparin, leukotrienes, and eosinophil-chemotactic factor of anaphylaxis. This
characterizes an allergic reaction, which is thus mediated by the binding of cellbound IgE with the antigens (allergens) that stimulated its production.
Actions of Antibodies
Some antibodies are able to agglutinate cells and to precipitate soluble antigens, thus
neutralizing their harmful effects on the body (Figure,2). Although phagocytosis of
microorganisms and other particles occurs spontaneously this event is greatly
stimulated when they are covered by antibodies produced against them, a
phenomenon called opsonization (Figure ,2). Opsonization occurs because
macrophages, neutrophils, and eosinophils have receptors for the Fc region of IgG on
their surfaces. Antigen–antibody complexes and some antigens activate the
complement system, a group of around 20 plasma proteins produced mainly in the
liver and activated through a cascade of reactions. One of the most important proteins
of this system is the component called C3. To defend the body against foreign
molecules or cells, the complement system may (1) stimulate phagocytosis of
bacteria or other microorganisms because of opsonization due to the binding of C3
fragments to specific C3 receptors present on the surface of phagocytic cells (Figure
,2).
(2) Induce lysis of microorganisms by acting on their cell membranes (Figure ,2).
4
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
Mechanisms of antigen inactivation. (1) Agglutination, in which antibodies bind to
antigens, forming aggregates and reducing the amount of free antigens; aggregates
may be ingested by phagocytes; (2) opsonization of antigens by complement
stimulates their phagocytosis; (3) opsonization of antigens by antibodies stimulates
phagocytosis; (4) neutralization, in which the binding of antibody to microorganisms
blocks their adhesion to cells and inactivates toxins; (5) cytotoxicity mediated by
cells, which involves antibodies adhering to the surface of worms activating cells of
the immune system (macrophages and eosinophils) and inducing them to liberate
molecules that attack the surface of the animal; (6) complement activation, in which
the binding of antibodies to the initial protein of the complement system triggers the
complement cascade and causes cell lysis.
Cells of the Immune System
The primary cells that participate in the immune response are lymphocytes,
plasma cells, mast cells, neutrophils, eosinophils, and cells of the mononuclear
phagocyte system. Antigen-presenting cells, a group of very diverse cell types, assist
other cells in the immune response. This group includes, among other cells,
lymphocytes, macrophages, and dendritic cells.
Lymphocytes
Lymphocytes are classified as B,T, or natural killer (NK) cells. The B and T
cells are the only cells that have the ability to selectively recognize a specific epitope
among a vast number of different epitopes (of the order of 10 18). B and T cells differ
based on their life history, surface receptors, and behavior during an immune
response. Although B and T cells are morphologically indistinguishable in either the
light or electron microscope, they can be distinguished by immunocytochemical
methods because they have different surface proteins (markers). The precursors of all
5
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
lymphocyte types originate in the bone marrow; some lymphocytes mature and
become functional in the bone marrow, and after leaving the bone marrow enter the
blood circulation to colonize connective tissues, epithelia, lymphoid nodules, and
lymphoid organs. These are the B lymphocytes (Figure ,3). T lymphocyte
precursors, on the other hand, leave the bone marrow, and through the blood
circulation reach the thymus where they undergo intense proliferation and
differentiation or die by apoptosis. After their final maturation, T cells leave the
thymus and are distributed throughout the body in connective tissues and lymphoid
organs (Figure ,3). Because of their function in lymphocyte production and
maturation, the bone marrow and the thymus are called the primary or central
lymphoid organs. The other lymphoid structures are the secondary or peripheral
lymphoid organs (spleen, lymph nodes, solitary lymphoid nodules, tonsils, appendix,
and Peyer's patches of the ileum). B and T cells are not anchored in the lymphoid
organs; instead, they continuously move from one location to another, a process
known as lymphocyte recirculation. B and T cells are not uniformly distributed in
the lymphoid system but occupy preferential sites in these organs.
(Figure ,3):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.
6
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
Approximate Percentage of B and T Lymphocytes in Lymphoid Organs.
Lymphoid Organ
T Lymphocytes, (%)
B Lymphocytes, (%)
Thymus
100
0
Bone marrow
10
90
Spleen
45
55
Lymph nodes
60
40
Blood
75
35
Each B lymphocyte that leaves the bone marrow or each T lymphocyte that
leaves the thymus has just one type of surface receptor that recognizes a specific
epitope.
B Lymphocytes
In B lymphocytes, the surface receptors able to recognize antigens are
monomeric molecules of IgM; each B cell is covered by about 150,000 molecules of
IgM. The encounter of a B lymphocyte with the epitope it recognizes leads to several
cycles of cell proliferation, followed by a redifferentiation of most of these
lymphocytes into plasma cells. This population of plasma cells secretes antibodies
against the same epitope as that of the B cell that originated them. In most cases, the
activation of B cells requires the assistance of a subclass of T lymphocytes known as
T-helper lymphocytes. Not all activated B cells, however, become plasma cells;
some remain B memory lymphocytes, which react rapidly to a second exposure to
the same epitope.
T Lymphocytes
T cells constitute 65–75% of blood lymphocytes. To recognize epitopes, all T
cells have on their surfaces a molecule called a T cell receptor (TCR). In contrast to
B cells, which recognize soluble antigens or antigens present on cell surfaces, T
lymphocytes recognize only epitopes (mostly small peptides) that form complexes
with special proteins of the cell surface of other cells .
The two main subpopulations of T cells are helper and cytotoxic
lymphocytes (CTLs). Helper cells play very important roles in the immune
response, being responsible for cytokine production, interaction with B cells to
7
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
promote their differentiation into plasma cells, activation of macrophages to
phagocytose, activation of cytotoxic lymphocytes, and induction of an
inflammatory reaction. Many of these actions are mediated by cytokines.
Helper cells have a marker called CD4 on their surfaces and are, hence, called
CD4+ T cells. Cytotoxic, or CD8+ T cells, can act against foreign cells or virusinfected cells by means of two main mechanisms. In one, they attach to the cells to
be killed and release proteins called perforins that create holes in the cell
membrane of the target cell, with consequent cell lysis. In the other, they attach to
a cell and kill it by triggering mechanisms that induce programmed cell death, or
apoptosis. The first encounter of a CD4+ or CD8+ T cell with its specific epitope is
followed by amplification of that clone; some of the cells of this increased
population become effector cells and some remain memory helper or memory
cytotoxic T cells, reacting rapidly to the next presentation of the same epitope.
Natural Killer Cells
The natural killer lymphocytes lack the marker molecules characteristic of B
and T cells. They comprise about 10–15% of the lymphocytes of circulating blood.
Their name derives from the fact that they attack virus-infected cells, transplanted
cells, and cancer cells without previous stimulation; for this reason they are involved
in what is called an innate immune
Antigen-Presenting Cells (APCs)
APCs are found in many tissues and constitute a heterogeneous cell population
that includes B lymphocytes, macrophages, and dendritic cells. The dendritic cells
(not to be confused with cells of the nervous tissue) are present within the epidermis
(where they are called Langerhans cells), within other epithelia, and within
lymphoid organs. A common feature of APCs is the presence of class II MHC
molecules on their surfaces. CD4+ T (helper) cells interact with complexes formed by
peptides and class II MHC molecules on APCs, whereas CD8+ T (cytotoxic) cells
interact with complexes of peptides with class I MHC molecules that can be
presented by any nucleated cell. APCs, being recognized by helper lymphocytes, are,
thus, essential for the triggering and development of a complex immune response.
The Langerhans cells of the epidermis constitute a very efficient system for
trapping antigens that happen to enter the epidermis. These cells have many processes
and upon capturing antigens, they retract the processes, move toward the dermis, and
may enter a lymphatic vessel.
8
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
Types of Immune Responses
The two basic types of immune responses are the innate response and the
adaptive response. The innate response, which occurs through the action of
neutrophils, macrophages, mast cells, and natural killer cells, is fast, nonspecific, and
older from an evolutionary point of view. It does not produce memory cells. The
adaptive response, which depends on the initial recognition of antigens by B and T
cells, is much more complex, is slower and specific, produces memory cells, and is a
more recent evolutionary development.
The adaptive mechanisms that lead to the elimination of antigens are classified as
humoral or cellular responses. Humoral immunity is accomplished by antibodies
produced by plasma cells derived from clones of activated B lymphocytes. Cellular
immunity is mediated by T lymphocytes that
(1) secrete cytokines that act on B lymphocytes, on other T cells, and on
inflammatory cells such as macrophages and neutrophils.
(2) attack foreign cells or cells that exhibit foreign epitopes on their surfaces, such as
cells infected by viruses or parasites, and tumor cells. With few exceptions, both
types of immune response are activated when foreign epitopes are recognized by
lymphocytes.
Lymphoid Organs: Introduction
 The cells of the immune system
(1) Are distributed throughout the body in the blood, lymph, and epithelial and
connective tissues.
(2) Are organized as differently sized organs called lymphoid organs—the lymph
nodes, the spleen, the thymus, and the bone marrow.
(3) Diffuse lymphoid tissue is especially prominent in the mucosa of the
gastrointestinal and respiratory systems. It is organized as non encapsulated clusters
of lymphoid cells or as lymphoid (lymphatic) nodules. Diffuse lymphoid tissue is
collectively called mucosa-associated lymphoid tissue (MALT).
 MALT consists of two major types, bronchus-associated lymphoid tissue
(BALT) and gutassociated lymphoid tissue (GALT). Both types possess
lymphoid nodules that are isolated from one another, except in the case of Peyer
patches.
 C. Lymphoid (lymphatic) nodules are transitory dense spherical accumulations
of lymphocyte (mostly B cells). The dark, peripheral region of nodules (corona) is
composed mainly of small, newly formed lymphocytes. Lymphoid nodules of the
9
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
GALT are isolated from the lumina of their respective tracts by microfold (M)
cells, which transfer antigens from the lumen and present them (without
processing them into epitopes) to lymphocytes and macrophages lying in deep
invaginations of their basal cell surfaces. From here, an appropriate immune
response is mounted by lymphoid tissue in the underlying lamina propria.
1-Secondary nodules, formed in response to an antigenic challenge, have a lightly
staining central area called the germinal center, which is composed of B lymphocytes
(lymphoblasts [centroblasts] as well as centrocytes). A darker region, known as the
mantle (corona), is composed of resting B cells that are being displaced from the
germinal center by the newly formed B cells. In addition to centroblasts and
centrocytes, the germinal center houses B memory cells, plasma cells, migrating
dendritic cells, follicular dendritic cells, macrophages, and reticular cells.
2. Primary nodules lack germinal centers and are composed of resting B memory
cells,

Lymphatic nodules are usually found in structures associated with the
alimentary canal such as the tonsils, ileum and vermiform appendix.
Generally, nodules are dispersed singly in a random manner. In the alimentary
canal, however, some aggregations of nodules are found in specific locations.
These include the following:
• Tonsils form a ring of lymphatic tissue at the entrance of the oropharynx. The
pharyngeal tonsils (adenoids)(located in the roof of the pharynx), the palatine
tonsils (or simply the tonsils, located on either side of the pharynx and between the
palatopharyngeal and palatoglossal arches), and the lingual tonsils at the base of the
tongue all contain aggregates of lymphatic nodules.
The palatine tonsils consist of dense accumulations of lymphatic tissue located in
the mucous membrane. The squamous epithelium that forms the surface of the tonsil
dips into the underlying connective tissue in numerous places, forming tonsillar
crypts .The walls of these crypts usually possess numerous lymphatic nodules. Like
other aggregations of lymph nodules, tonsils do not possess afferent lymphatic
vessels; however, lymph drains from the lymphatic tissue of the tonsil via efferent
lymphatic vessels.
• Peyer’s patches are located in the ileum (distal portion of the small intestine) and
consist of numerous aggregations of lymphatic nodules containing T and B
lymphocytes.In addition, numerous isolated single (solitary) lymph nodules are
located along both large and small intestines.
• The vermiform appendix arises from the cecum. The lamina propria is heavily
infiltrated with lymphocytes and contains numerous lymphatic nodules.
10
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
Lymph Nodes
Lymph nodes are small encapsulated organs located along the pathway of
lymphatic vessels. Lymph nodes are small, bean-shaped, encapsulated lymphatic
organs. They range in size from about 1 mm (barely visible with the unaided eye) to
about 1 to 2 cm in their longest dimension. Lymph nodes are interposed along
lymphatic vessels and serve as filters through which lymph percolates on its way to the
blood vascular system. Although widely distributed throughout the body, they are
concentrated in certain regions such as the axilla, groin, and mesenteries.
Two types of lymphatic vessels serve the lymph node:
• Afferent lymphatic vessels convey lymph toward the node and enter it at various
points on the convex surface of the capsule.
• Efferent lymphatic vessels convey lymph away from the node and leave at the
hilum, a depression on the concave surface of the node that also serves as the
entrance and exit for blood vessels and nerves.
The supporting elements of the lymph node are:
• capsule, composed of dense connective tissue that surrounds the node;
The cells of the reticular meshwork appear as stellate or elongated cells with an oval
euchromatic nucleus and a small amount of acidophilic cytoplasm. These cells can
take up dyes and colloidal materials. Using immunocytochemistry and transmission
electron microscopy, several populations of cells have been identified.
• Reticular cells are indistinguishable from typical fibroblasts. These cells synthesize
and secrete type III collagen (reticular fibers) and the associated ground substance
that forms the stroma observed with the light microscope . Besides their supporting
role, they express surface molecules and produce substances that attract T cells, B
cells, and dendritic cells.
• Dendritic cells (DCs) are unique bone marrow–derived APCs. DCs monitor the local
environment for foreign substances that they then process and present to antigen
specific T cells. Costimulatory molecules necessary for activation of T cells. In the
lymph node, DCs are usually localized in T lymphocyte–rich areas.
• Macrophages are both phagocytic and antigen-presenting cells costimulatory
molecules are much lower than those of the dendritic cells, making them less efficient
APCs. Instead, they have an immense capacity for endocytosis and digestion of
internalized materials. The
11
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
• Follicular dendritic cells (FDCs) have multiple, thin, hairlike branching
cytoplasmic processes that interdigitate between B lymphocytes in the germinal
centers
 General Architecture of the Lymph Node
The parenchyma of the lymph node is divided into a cortex and medulla . The cortex
forms the outer portion of the node except at the hilum. It consists of a dense mass of
lymphatic tissue (reticular framework, dendritic cells, follicular dendritic cells,
lymphocytes, macrophages, and plasma cells) and lymphatic sinuses, the lymph
channels. The medulla is the inner part of the lymph node.
As elsewhere, the lymphatic nodules of the cortex are designated primary nodules if
they consist chiefly of small lymphocytes and secondary nodules if they possess a
germinal center. Lymphatic nodules are found in the outer part of the cortex, called the
superficial (nodular) cortex . The portion of the cortex between the medulla and
superficial cortex is free of nodules; it is called the deep cortex (paracortex). This
region contains most of the T cells in the lymph node. Because of its dependence on
the thymus, perinatal thymectomy in animals results in a poorly developed deep
cortex. On the basis of this observation, the deep cortex is also called the thymus
dependent cortex. The medulla of the lymph node consists of the medullary cords
and medullary sinuses. The medulla, the inner part of the lymph node, consists of
cords of lymphatic tissue separated by lymphatic sinuses called medullary sinuses. As
described above, a network of reticular cells and fibers traverses the medullary cords
and medullary sinuses and serves as the framework of the parenchyma. In addition to
reticular cells, the medullary cords contain lymphocytes (mostly B lymphocytes),
macrophages, dendritic, and plasma cells. The medullary sinuses converge near the
hilum, where they drain into efferent lymphatic vessels.
 Filtration of lymph in the lymph node occurs within a network of
interconnected lymphatic channels called sinuses.
There are three types of lymphatic channels called sinuses in the lymph node. Just
beneath the capsule of the lymphnode is a sinus interposed between the capsule and
the cortical lymphocytes called the subcapsular (cortical) sinus Afferent lymphatic
vessels drain lymph into this sinus. Trabecular sinuses that originate from the
subcapsular sinuses extend through the cortex along the trabeculae and drain into
medullary sinuses. Lymphocytes and macrophages or their processes readily pass
back and forth between the lymphatic sinuses and the parenchyma of the node. The
sinuses have a lining of endothelium that is continuous where it is directly adjacent to
the connective tissue of the capsule or trabeculae but discontinuous where it faces the
lymphatic parenchyma. Although a macrophage may reside in the lymphatic
parenchyma, it often sends pseudopods (long cytoplasmic processes) into the sinus
through these endothelial discontinuities. These pseuAfferent lymphatic vessels drain
12
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
lymph into this sinus. Trabecular sinuses that originate from the subcapsular sinuses
extend through the cortex along the trabeculae and drain into medullary sinuses.
Lymphocytes and macrophages or their processes readily pass back and forth between
the lymphatic sinuses and the parenchyma of the node. The sinuses have a lining of
endothelium that is continuous where it is directly adjacent to the connective tissue of
the capsule or trabeculae but discontinuous where it faces the lymphatic parenchyma.
Although a macrophage may reside in the lymphatic parenchyma, it often
sendspseudopods (long cytoplasmic processes) into the sinus through these endothelial
discontinuities. These pseudopods monitor the lymph as it percolates through the
sinus.
Thymus
The thymus is a lymphoepithelial organ located in the superior mediastinum. The
thymus is a bilobed organ located in the superior mediastinum. It develops bilaterally
from the third (and sometimes also the fourth) branchial (oropharyngeal) pouch.
During development, the epithelium invaginates, and the thymic rudiment grows
caudally as a tubular projection of the endodermal epithelium into the mediastinum of
the chest. The advancing tip proliferates and ultimately becomes disconnected from the
branchial epithelium. Multipotential lymphoid stem cells from the bone marrow are
destined to develop into immunocompetent T cells that invade the epithelial rudiment
and occupy spaces between the epithelial cells so that the thymus develops into a
lymphoepithelial organ. The thymus is fully formed and functional at birth. It persists
as a large organ until about the time of puberty,
when T-cell differentiation and proliferation are reduced and most of the lymphatic
tissue is replaced by adipose tissue (involution). The organ can be restimulated under
conditions that demand rapid T-cell proliferation. General Architecture of the Thymus
Connective tissue surrounds the thymus and subdivides it into thymic lobules. The
thymus possesses a thin connective tissue capsule from which trabeculae extend into
the parenchyma of the organ. The capsule and trabeculae contain blood vessels,
efferent (but not afferent) lymphatic vessels, and nerves. In addition to collagen fibers
and fibroblasts, the connective tissue of the thymus contains variable numbers of
plasma cells, granulocytes, lymphocytes, mast cells, adipose cells, and macrophages,
the trabeculae establish domains in the thymus called thymic lobules.
The thymus possesses no lymphoid nodules; instead, it is divided into an
• outer darker staining cortex, composed of epithelial reticular cells, macrophages,
and small T lymphocytes (thymocytes), and an
• inner lighter staining medulla consisting of large T lymphocytes, epithelial
reticular cells, and thymic (Hassall’s) corpuscles
13
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
 The thymic medulla is continuous between adjacent lobules and contains large
numbers of epithelial reticular cells and mature T cells, which are loosely packed,
causing the medulla to stain lighter than the cortex.
 It also contains whorl-like accretions of epithelial reticular cells called Hassall
corpuscles (thymic corpuscles). These structures display various stages of
keratinization and increase in number with age. Their function is unknown,
although it has been shown that these epithelial reticular cells manufacture thymic
stromal lymphopoietin (TSLP), a cytokine that facilitates dendritic cell maturation.
 Mature T cells exit the thymus via venules and efferent lymphatic vessels from the
thymic medulla. The T cells then migrate to secondary lymphoid structures.
Spleen
 A simple squamous epithelium (peritoneum) covers the dense irregular collagenous
connective tissue capsule of the spleen, which sends trabeculae into the substance
of the spleen to form a supportive framework. The spleen is similar to lymph nodes
in that it possesses a hilum but differs from both the thymus and lymph nodes in that
it lacks a cortex and medulla. It further differs from lymph nodes because it has no
afferent lymphatic vessels.The spleen is divided into red pulp and white pulp; the
latter contains lymphoid elements. These two regions are separated from each other
by the marginal zone.
 Function—Spleen. The spleen filters blood, stores erythrocytes, phagocytoses
damaged and aged erythrocytes, and is a site of proliferation of B and T
lymphocytes and the production of antibodies by plasma cells.
Vascularization of the spleen is derived from the:
a. splenic artery, which enters the hilum and gives rise to trabecular arteries.
Trabecular arteries leave the trabeculae, become invested by a periarterial
lymphatic sheath (PALS, described later), and are known as central arteries.
b. Central arteries branch but maintain their lymphatic sheath until they leave the
white pulp to form several straight penicillar arteries.
c. Penicillar arteries enter the red pulp. They have three regions: pulp arterioles,
macrophage-sheathed arterioles, and terminal arterial capillaries. These last named
vessels either drain directly into the splenic sinusoids (closed circulation) or terminate
as open-ended vessels within the splenic cords of the red pulp (open circulation).
d. Splenic sinusoids are drained by pulp veins, which are tributaries of the trabecular
veins; these in turn drain into the splenic vein, which exits the spleen at the hilum.
 Structure—Spleen
14
Collage of medicine
9\11\2015
Anatomy and histology department
Dr.Hameda A.Gahzi
a. White pulp of the spleen includes all of the organ’s lymphoid tissue (diffuse and
nodular), such as lymphoid nodules (mostly B cells) and PALS (mostly T cells)
around the central arteries. It also contains macrophages and other APCs.
b. The marginal zone of the spleen
(1) is a sinusoidal region between the red and white pulps at the periphery of the
PALS.
(2) receives blood from capillary loops derived from the central artery and thus is the
first site where blood contacts the splenic parenchyma.
(3) is richly supplied by avidly phagocytic macrophages and other APCs.
(4) is the region where circulating T and B lymphocytes enter the spleen before
becoming segregated to their specific locations within the organ and where
interdigitating dendritic cells are able to display their MHC-epitope complex for
recognition by T cells.
c. Red pulp of the spleen (Figure 12.4) is composed of an interconnected network of
sinusoids supported by a loose type of reticular tissue (splenic cords).
(1) Sinusoids
(a) are lined by long fusiform endothelial cells separated by relatively large
bloodcontaining intercellular spaces.
(b) have a discontinuous basal lamina underlying
circumferentially arranged ribs of reticular fibrils.
the endothelium and
(2) Splenic cords (cords of Billroth) contain plasma cells, stellate reticular cells, blood
cells, and macrophages enmeshed within the spaces of the reticular fiber network.
Processes of the macrophages enter the lumina of the sinusoids through the spaces
between the endothelial cells.
15