HISTOLOGY SCT 1 ST

PART 3
By Yuliya Konotoptseva
Lymphatic
tissue
■ Consists of group of cells tissues and organs that monitor body surfaces and internal fluid
compartment and react with the presence of potentially harmful substances.
■ Lymphocytes are the definitive cell type and effector cells. Plus, diffuse lymphatic tissue,
lymphatic nodule, lymph nodes, spleen, bone marrow and thymus, plus mucosa associated
lymphatic tissue, such as tonsils and peyers patches.
■ Lymphatic tissue serves for lymphocytes a site of differentiation. In addition, thymus, bone
marrow and GALT is where they are also educated
■ There are 2 types of lymphoid organs:
– Primary lymphoid organs, also called central, the sites where lymphocytes differentiate
and develop ability to recognize foreign antigens and distinguish self from non self
– Secondary, also called peripheral, where mature lymphocytes encounter foreign
antigens and the immune response takes place.
■ 2 types of immune responses : innate (non specific) the one that was always there, and
adaptive (specific) the one that is a memory.
■ Cells of the immune system : lymphocytes (B, T and NK), monocytes, macrophages,
neutrophils, basophils, eosinophils, reticular cells, dendritic cells, Langerhans cells,
epithelioreticular cells, etc.
Antigen
■ any substance that can induce a specific immune response.
■ The body is constantly exposed to pathogenic (disease causing) organisms and hazardous
substances from the external environment (infectious microorganisms, toxins, and foreign cells
and tissues). In addition, changes may occur in cells (such as transformation of normal cells into
cancerous cells) that give them characteristics of foreign cells.
■ An immune response is generated against a specific antigen, which can be a soluble substance
(e.g., a foreign protein, polysaccharide, or toxin) or an infectious organism, foreign tissue, or
transformed tissue.
■ Most antigens must be “processed” by cells of the immune system before other cells can mount
the immune response.
■ the innate immunity represents the first line of defense against microbial aggression. It consists of
(1) physical barriers (e.g., the skin and mucous membranes) that prevent foreign organisms from
invading the tissues, (2) chemical defenses (e.g., low pH ) that destroy many invading
microorganisms, (3) various secretory substances (e.g., thiocyanate in saliva, lysozymes,
interferons, fibronectin, and complement in serum) that neutralize foreign cells, and (4) phagocytic
cells (e.g., macrophages, neutrophils, and monocytes) and natural killer (NK) cells.
■ With specific (adaptive) immunity, if nonspecific defenses fail, the immune system provides specific,
or adaptive, defenses that target specific invaders. The initial contact with a specific antigen or
foreign agent initiates a chain of reactions that involve effector cells of the immune system and
frequently leads to a state of immune “memory.” Adaptive immunity induces acquired resistance
against microbial aggression through random somatic rearrangements of genes that encode
immunoglobulins and specific receptors on T lymphocytes (i.e., T-cell receptors, or TCRs). During
adaptive immune responses, specific B and T lymphocytes become activated to destroy invading
organisms.
■ Two types of specific defenses have been identified: Humoral response results in the production of
proteins called antibodies that mark invaders for destruction by other immune cells, and the cellular
immune response targets transformed and virus-infected cells for destruction by specific “killer”
cells.
Cells
■ Three major types of lymphocytes are recognized: B cells, T cells, and NK cells. Supporting cells
interact with lymphocytes and play important roles in the presentation of antigen to lymphocytes
and the regulation of immune responses. These cells include monocytes, macrophages,
neutrophils, basophils, eosinophils, reticular cells, dendritic cells, follicular dendritic cells,
Langerhans’ cells, and epithelioreticular cells.

■ Supporting cells in the lymphatic organs are organized into loose meshworks. In lymph nodules,
lymph nodes, and the spleen, reticular cells and the reticular fibers produced by these cells form
elaborate meshworks. Lymphocytes, macrophages, dendritic cells, follicular dendritic cells, and
other cells of the immune system reside in these meshworks and in the loose connective tissue of
the body; Langerhans’ cells are found only in the middle layers of epidermis. At these sites, they
carry out their mission of surveillance and defense. In the thymus, epithelioreticular cells form the
structural meshwork within the tissue. Despite their name, these cells neither produce nor are
related to reticular fibers.
Cluster of differentiation
■ Different lymphatic and hematopoietic tissue cells possess unique cell surface molecules.
These specific markers, called cluster of differentiation (CD) molecules, are designated by
numbers according to an international system that relates them to antigens expressed at
different stages of their differentiation. CD molecules can be visualized by
immunohistochemical methods using monoclonal antibodies and are useful in identifying
specific subtypes of lymphatic or hematopoietic cells. Some CD markers are expressed by cells
throughout their entire life; others are expressed only during one phase of differentiation or
during cell activation.
T- Lymphocytes
■ T lymphocytes (T cells) are named for the thymus, where they differentiate. They have a long
lifespan and are involved in cell-mediated immunity. They account for 60% to 80% of circulating
lymphocytes. T cells express CD2, CD3, CD5, and CD7 markers and T-cell receptors (TCRs);
however, they are subclassified according to the presence or absence of two other important
surface markers: CD4 and CD8.
■ • Helper CD4 T lymphocytes are T cells that also express CD4 markers. These cells are further
subdivided by their ability to secrete cytokines. Helper T cells that synthesize interleukin 2 (IL-2),
interferon (IFN-), and tumor necrosis factor (TNF-) are called TH1 cells. These cells interact with
cytotoxic CD8 T lymphocytes (CTLs), NK cells, and macrophages in cell-mediated immune
responses and are essential for controlling intracellular pathogens such as viruses and certain
microorganisms. The other group of helper T cells synthesize IL-4, IL-5, IL- 10, and IL-13 and are
called TH2 cells. They interact with B lymphocytes and are essential for initiating antibody-
mediatedimmune responses that control extracellular pathogens.
■ Cytotoxic CD8 T lymphocytes (CTLs) are T cells that also express CD8 markers. They kill other target
cells such as virus-infected cells, cancer-transformed cells, cells infected with intracellular
microorganisms, parasites, and transplanted cells.
■ Regulatory (suppressor) T lymphocytes represent a phenotypically diverse population of T
lymphocytes that can functionally suppress an immune response to foreign and self-antigen by
influencing the activity of other cells in the immune system. For example, T lymphocyte with CD4
CD25FOXP3 markers represent a classical example of the regulatory cells that can diminish the
ability of T lymphocytes to initiate immune responses. The FOXP3 marker indicates an expression of
forkhead family transcription factors that are characteristic of many T cells. Another tumor-associated
■ T lymphocyte with CD8CD45RO markers is able to suppress T-cell activation. Other suppressor T cells
may also function in suppressing B-cell differentiation and in regulating erythroid cell maturation in
the bone marrow.
B lymphocyte
■ B lymphocytes (B cells) are so named because they were first recognized as a separate population
in the bursa of Fabricius in birds or bursa-equivalent organs such as bone marrow and GALT in
mammals. They have variable life spans and are involved in the production and secretion of the
various circulating antibodies, also called immunoglobulins (Ig), the immune proteins associated
with humoral immunity.
■ B cells account for 20% to 30% of the circulating lymphocytes. In addition to secreting circulating
immunoglobulins, B cells express membrane-bound forms of immunoglobulin called B-cell
receptors (BCRs) that serve as the antigen-specific binding site. During differentiation, the BCR
isotope switches from immunoglobulin M (IgM) in immature B cells to immunoglobulin D(IgD) in
mature B cells.
■ B cells also express the major histocompatibility complex II (MHC II) molecules on the cell surface.
■ Their CD markers are CD9, CD19, and CD20.
NK cell
■ Natural killer (NK) cells, which develop from the same precursor cell as B and T cells, are named
for their ability to kill certain types of target cells. They constitute about 5% to 10% of circulating
lymphocytes.
■ They do not mature in the thymus; however, during their development, they are genetically
programmed to recognize transformed cells (i.e., cells infected with a virus or tumor cells). NK cells
kill target cells in a similar fashion to that of cytotoxic CD8 T lymphocytes.
■ After recognition of a transformed cell, they release perforins and granzymes (fragmentins),
substances that create channels in the cell’s plasma membrane, which induces them to self-
destruct (a process known as apoptosis).
■ Their specific markers include CD16a, CD56, and CD94.
Antigen presenting cells
■ Prestory: CD8+ T lymphocytes are MHC I restricted (cytotoxic), while CD4+ are MHC II
restricted.(helper)
■ MHC – Major histocompatibility complex : you have t cell receptor, that only recognizes antigen
when it is bound to MHC molecules. In addition, helper T cells, can only recognize antigen if they
are presented by APC… MHC molecules display small fragments of digested foreign proteins on
the surface of cells
■ Most APC belong to the mononuclear phagocytotic family. Almost all cell types can serve as some
form of APC. They are found in a variety of tissue types. Professional antigen-presenting cells,
including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells,
while other cell types can present antigens originating inside the cell to cytotoxic T cells.
■ APCs: macrophages, Kupffer cells in liver, Langerhans in epidermis, dendritic cells in spleen and
lymph nodes.
■ 2 APCs that do not belong to the MPS are B lymphocytes and type II and III epithelioreticular cells
in thymus.
■ Macrophages often fuse to form multinucleate, foreign body giant cells
■ Non-professional antigen presenting cells include all nucleated cell types in the body. They use an
MHC class I molecule
■ In general, an encounter with a given antigen triggers a response characterized as either a humoral
immune response (antibody production) or a cell-mediated immune response.
■ Typically, however, both cellular and humoral immune systems are involved, although one system
generally predominates, depending on the stimulus.
■ • Humoral (antibody-mediated) immunity is mediated by antibodies that act directly on an invading
agent. These antibodies are produced by plasma cells derived from B lymphocytes. In some
diseases (e.g., tetanus), a nonimmune person can be rendered immune by receiving an injection of
antibody purified from the blood of an immune person or animal. The effectiveness of this passive
transfer proves that it is the antibody that is responsible for the protection.
■ • Cell-mediated immunity is mediated by specific T lymphocytes that attack and destroy virus-
infected host cells or foreign cells. Cell-mediated immunity is important in the defense against viral,
fungal, and mycobacterial infections, as well as tumor cells. Cell-mediated immunity is also
responsible for transplant rejection.
■ Helper T and cytotoxic lymphocytes act as the immune system “patrols.” Both kinds of lymphocytes have
a T-cell receptor (TCR), a transmembrane protein whose exposed portion is on the T-cell membrane in
close proximity to the CD3 marker. The TCR recognizes antigen only when it is attached to “identification
molecules,” the MHC molecules. In addition, helper T lymphocytes can only recognize an antigen when
it is “presented” to them by cells called antigen-presenting cells (APCs). Cytotoxic T lymphocytes can
only recognize antigen on other body cells such as those transformed bycancer or infected with a virus.
■ The two classes of MHC molecules display peptides on the surface of cells. MHC I and MHC II molecules
are products of a “supergene” located on chromosome 6 in humans known as the major
histocompatibility gene complex. The expression of this gene complex produces molecules that are
specific not only to the individual cell that produces them but also to the tissue type and degree of
cellular differentiation.
■ MHC I is expressed on the surface of all nucleated cells and platelets.? MHC I molecules act as a target
to allow the elimination of abnormal host cells (e.g., virus-infected or transformed cancer cells). MHC I
molecules perform this function by displaying on their surface short fragments of all peptides tha are
actively synthesized by the cell. Therefore, all endogenous “self ” peptides are displayed on the surface
of every cell in the body, but viral or cancer-specific peptides are displayed only on the surface of
infected or transformed cells. The MHC I molecules present peptides fragments to cytotoxic CD8 T
lymphocytes.
■ MHC II is limited in its distribution. It is expressed on the surface of all APCs and is critical in immune
interactions. The MHC II molecules present partially digested, endocytosed foreign peptides to helper
CD4 T lymphocytes.
■ They begin as a network of blind
capillaries in loose CT. (most
Lymphatic
numerous beneath the epithelium of
skin and mucous vessels
membranes) Lymph vessels are
lined by endothelial cells, and have a
thin layer of smooth muscle,
and adventitia that bind the lymph
vessels to the surrounding tissue.
■ These vessels remove substances
and fluid from the extracellular
spaces of CT, thus producing lymph.
■ Walls of lymph vessels are more
permeable than blood capillaries, so
you will find large molecules,
antigens, etc.
■ Lymphocytes in the lymph enter
lymph nodes via afferent lymphatic
vessels, whereas those converted by
blood enter the node through
postcapillary venules (high
endothelial venules), then leave
through efferent lymphatic vessels.
■ Lymphocytes conveyed in the lymph enter lymph nodes via afferent lymphatic vessels, whereas
lymphocytes conveyed in the blood enter the node through the walls of postcapillary venules (high
endothelial venules [HEVs]; B and T cells migrate to and populate different regions within the
lymph node. Some lymphocytes pass through the substance of the node and leave via the efferent
lymphatic vessels, which lead to the right lymphatic trunk or to the thoracic duct. In turn, both of
these channels empty into the blood circulation at the junctions of the internal jugular and
subclavian veins at the base of the neck.
■ The lymphocytes are conveyed to and from the various lymphatic tissues via the blood vessels.
• The thymus is a primary lymphoid organ found within
the superior mediastinum, behind the upper part of
the sternum.
Thymus
• This organ is active in children, but at the start of
puberty, until old age, it starts to atrophy, producing
fewer T-cells.

• It has two lobes divided up into many lobules. The

outer, more darkly staining region is the cortex, and
this is highly cellular. The inner lighter staining region
is the medullar, and this region is less cellular. It has
an outer connective tissue capsule and septa.
• The cortex stains more darkly (is more basophilic)
than the medulla, because it contains more
lymphocytes than the medulla.

• The epithelial network in the cortex is more finely

branched than in the medulla - and this gives this
network the name 'reticular'.

• The epithelial cells are connected to each other by

desmosomes, and the intermediate filament protein
keratin is present in their cytoplasm
■ Bilobed organ, located in the superior mediastinum,
anterior to the heart and vessels.
■ Develops from the 3rd pharyngeal pouch.
■ Multipotential lymphoid stem cells from the bone marrow,
that are destined to become immunocompetent T cells
invade the epithelial rudiment.
■ It persists as a large organ until puberty, and later is
replaced by adipose tissue
■ It possesses a thin CT capsule from which trabeculae
extend into the parenchyma of the organ. The capsule and
trabecula contain blood vessels, EFFERENT lymphatic
vessels, nerves etc
■ This trabecula establishes thymic lobules. (that are not
true lobules)
■ The outer portion, cortex is marked basophilic in H/E,
because of closely packed developing T lymphocytes, with
nuclei.
■ These T lymphocytes, aka thymocytes, occupy space within
extensive meshwork of epithelioreticular cells
Stages:

■ Thymus epithelialis – embryonic life

■ Thymus lymphaticus – after invasion of lymphocytes
■ Thymus adiposus - after puberty
■ Epithelioreticular cells are both, epithelial and reticular. They provide
framework for the developing T lymphocytes. However, reticular CT is
not present in the thymus.
■ There are 6 types of epithelioreticular cells :
1) Type I , are at the boundary of cortex and CT capsule. They serve
to separate the thymic parenchyma from the CT. They have
occluding junctions, hence the function barrier.
2) Type II, are within the cortex, unlike type I, they express MHC I and
II. They compartmentalize the cortex into isolated areas for the
developing T cells.
3) Type III, are at the boundary between cortex and medulla,
functional barrier, express MHC I and II
Epithelial reticular cells are the primary cell involved with making sure
that no T cells are allowed to survive that will attack the body's own
cells. It does this by expressing a very large proportion of its genome,
and expressing as many 'self' proteins on its cell membrane as possible.
As the T cells migrate from the cortex of the thymus to the medulla, they
come into contact with many epithelial reticular cells, and if they
recognise self proteins as a pathogen, then the epithelial cells destroy
them.
You will find macrophages within the thymic cortex , they are
responsible for the phagocytosis of uneducated T cells. These T cells
are programmed to die, before leaving cortex. Around 98% of T cells,
undergo this apoptosis and phagocytosed by macrophages. PAS
reaction stains those macrophages because of the lysosomes
Thymic medulla
■ 4) type IV E.R cells, between
cortex and medulla closer to
type III cells. Create a barrier
■ 5) type V cells, throughout
medulla, compartmentalize
the groups of lymphocytes
■ 6) type VI, form the most
characteristic feature of the
medulla, the thymic or
Hassall's corpuscle. These
are isolated masses of
closely packed type VI E.R
cells that exhibit flat nuclei.
Function is not fully
understood, it is thought to
produce Interleukins 4 and
& that are needed for
differentiation of T cells.
Thymic Hassal corpuscle
■ Thymic corpuscles are isolated masses of closely packed, concentrically arranged type VI
epithelioreticular cells that exhibit flattened nuclei. TEM studies of these cells reveal keratohyalin
granules, bundles of cytoplasmic intermediate filaments, and lipid droplets. The cells are joined
by desmosomes. The center of a thymic corpuscle may display evidence of keratinization, not a
surprising feature for cells developed from oropharyngeal epithelium.
■ Thymic corpuscles are unique, antigenically distinct, and functionally active multicellular
components of the medulla. Although the function of thymic corpuscles is not fully understood, it
is thought that thymic corpuscles produce interleukins (IL-4 and IL-7) that function in thymic
differentiation and education of T lymphocytes.
 Blood – thymus barrier
■ Protects developing T cells from
exposure to antigens
■ Components are :
■ 1) lining endothelium of the
capillary wall, which is continues
type
■ 2) basal lamina of endothelial
cells
■ 3) pericytes ( part of the capillary
wall)
■ 4) macrophages in perivascular
CT
■ 5) type I epithelioreticular cells
T- cell education
■ Stem cell maturation and differentiation into immunocompetent T cells is called thymic cell
education. This process is characterized by the expression and deletion of specific surface CD
antigens.
■ The expression of CD2 and CD7 molecules on the T-cell surface indicates an early stage of
differentiation (doublenegativestage). The double-negative term refers to lack of both CD4 and CD8
molecules. This early stage is followed by the expression of the CD1 molecule, which indicates the
middle stage of T-cell differentiation. As maturation progresses, the T-cells express TCRs, CD3, and
both CD4 and CD8 molecules. This is the double-positive stage of T-cells differentiation.
■ The cells are presented with self and foreign antigens by type I and III epithelioreticular cells. If the
lymphocytes recognizes self MHC molecules, and self or foreign antigen it will survive – POSITIVE
SELECTION. If not, it will die.
■ Cells that pass positive selection test leave cortex and enter medulla. Here they undergo a process
in which cells that recognize self antigens are eliminated – NEGATIVE SELECTION.
■ The cells that survive become either cytotoxic CD8 T lymphocytes (by losing CD4 and retaining CD8)
or helper CD4 T lymphocytes (by losing CD8 and retaining CD4). This stage is called the single-
positive stage of T-cells differentiation.
■ Now the cells leave the thymus by passing from the medulla into the blood circulation. The process
of thymic cell education is promoted by substances secreted by the epithelioreticular cells,
including interleukins (IL-4 and IL-7), colony-stimulating factors, and interferon .
Thymus
lymphaticus
■ h/e
Lymphatic tissue
■ The alimentary canal, respiratory passages and
genitourinary tract are guarded by
accumulations of lymphatic tissue, that are not
enclosed in a capsule.
■ Lymphocytes and other free cells of the tissue
are found in basal lamina.
■ This form of lymphatic tissue is known as
diffuse lymphatic tissue or mucosa –
associated lymphatic tissue (MALT).
■ After contact with antigen, they travel to lymph
node, where they undergo proliferation and
differentiation
Lymphatic nodules
■ In addition to diffuse lymphatic tissue, localized
concentration of lymphocytes are commonly found in
the walls of previous structures. These concentrations
are known as lymphatic nodules or follicles. They are
sharply defined, But are NOT capsulated.
■ A lymphatic nodule consisting chiefly of lymphocytes is
called primary nodule.
■ However, most nodules are secondary nodules, and
have distinctive features: - germinal center , which is
located in the center; it is lightly stained. The germinal
center develops, when a lymphocytes that has
recognized an antigen, returns to a primary nodule and
undergoes proliferation. Why is it lightly stained? Vast
number of large immature lymphocytes, which means
they have dispersed euchromatin. - mantle zone, or
corona, which represents outer ring of small
lymphocytes.
■ Generally, nodules are dispersed in a random manner. However, in the alimentary canal,
those aggregations are found in specific sites:
■ 1) Tonsils, which form a ring of lymphatic tissue at the entrance of the oropharynx.
Pharyngeal tonsils, or adenoids, located at the roof of pharynx. The palatine are on either
side of pharynx, or between palatopharyngeal and palatoglossal arches. The lingual tonsils ,
are at the base of the tongue
■ 2) Peyer’s patches, which are in the ileum.
■ 3) vermiform appendix, from cecum.
■ BALT, GALT, MALT.
 Large intestine H/E

mucosa

submucosa

Muscularis externa circular

longitudinal
Large intestine H/E
Palatine tonsils

■ The ring of Waldeyer

■ The tonsils are part of MALT
■ Epithelium is stratified squamous non keratinized, lamina propria has secondary
lymphatic follicles.
■ Deep elongated crypts.
■ In the secondary follicle: germinal center B cell maturation dominant, mantle zone T
cells.
Lingual tonsils

■ Same as palatine, but the crypts are not as deep; and no cellular debris.
■ Small, bean-shaped, encapsulated lymphatic
organs. That range in size from 1mm to about 2
cm. They serve as filters. Lymph nodes
■ Although widely distributed everywhere, mostly
found in axilla, groin, mesenteries.
2 types of lymphatic vessels serve the lymph node:
1) afferent , that convey lymph toward the lymph
node, and enter at various points in capsule.
2) efferent, that convey lymph away from the node,
and leave through hilum.
The supporting elements of node are : 1) capsule,
composed of dense CT., 2) trabeculae, dense CT., 3)
reticular tissue, composed of reticular cells and
fibers, to form a fine reticular meshwork
The nodes are covered by a capsule of dense
connective tissue, and have capsular extensions, of
connective tissue, called the trabeculae, which
provide support for blood vessels entering into the
nodes.
Lymph, containing micro-organisms, soluble antigens,
antigen presenting cells, and a few B-cells, enters the
lymph node via afferent lymphatic vessels which enter
the subcapsular sinus. It then runs through trabecular
sinuses into medullary sinuses and leaves through
the efferent lymphatic vessels, at the Hilium as
efferent lymph. This contains lots of T-lymphocytes, B-
lymphocytes, plasma cells and antibody.
Cells of reticular meshwork
■ The cortex is divided into an outer and an inner cortex
■ The outer cortex has lymphatic nodules that mostly contain B-cells. Small lymphocytes sit in the
spaces between the reticular fibre meshwork in the cortex.
■ The inner cortex contains mostly T-cells.
■ The deep cortical, and medullary cords contain B-cells and plasma cells. Plasma cells live for 3
days, and make IgG type antibodies.
■ Reticular cells, synthesize and secrete collagen III (reticular fibers). Have supporting role, plus
express surface molecules that will attract B, T lymphocytes and dendritic cells.
■ Dendritic cells (DCs), unique bone marrow derived APCs. Monitor local environment for foreign
substances, that they then process and present to T cells. Can present virtually any form of
protein antigen on both MHC I and II. Next to T-cell rich area
■ Macrophages, both phagocytic and antigen-presenting cells that express MHC I, MHC II, and
costimulatory molecules. However, the expression levels of MHC II and 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.
■ Follicular dendritic cells, their processes are inbetween the B cells in germinal centers. Not APCs,
because they lack MHC II. the antigen is not generally endocytosed, as it is by the macrophage.
FDCs are thus not APCs because they lack MHC II molecules.
■ Parenchyma is divided into a cortex
and medulla. General architecture of lymph
■ As elsewhere, the lymphatic nodules
of the cortex are primary nodules if
node
they consists of small lymphocytes,
and secondary, if they posses
germinal center.
■ Those nodules in the outer part of
cortex, are known as superficial or
nodular cortex.
■ The portion of cortex that is between
the medulla and superficial cortex is
known as paracortex. This region
contains most of they T cells. (
thymus – dependent cortex)
■ The medulla consists of medullary
cords and sinuses.
■ Medullary cords contain B cells,
macrophages, dendritic cells and
plasma cells.
■ There are 3 types of lymphatic channels, called sinuses in the lymph node.
■ Just beneath the capsule, there is subcapsular or cortical sinus, afferent lymphatic vessels
drain into here.
■ Trabecular sinus originate from the subcapsular sinuses extend through the cortex and drain
into medullary sinuses.
■ The sinuses have a lining of endothelium that is continuous where it is directly adjacent to
CT, and discontinuous where there is lymphatic tissue. Macrophages often send their
pseudopods into sinuses to monitor the lymph.
■ Although some lymphocytes enter the node through afferent l.v., most (90%) enter through
the walls of postcapillary venule located in the deep cortex. Because those capillaries are
lined by cuboidal or columnar endothelial cells, they are referred as high endothelial venules,
HEV.
Lymph node h/e
Spleen
■ A size of a clenched fist and is the largest lymphatic organ. Located in the upper left
quadrant of the abdominal cavity, and has a rich blood supply.
■ Spleen has both morphological and immunological filtering functions.
■ The spleen is enclosed by dense CT capsule, from which trabeculae extend into the
parenchyma. The CT contain myofibroblast. These contractile cells also produce extracellular
CT fibers.
■ They hilum is located on the medial surface of the spleen, and is the site of passage for
splenic artery and vein, nerves and lymphatic vessels. The latter one originate in white pulp.
■ There are 2 pulps in spleen: white and red.
■ Like the lymph nodes, it also has a hilus (hilium) which is where the major blood
vessels enter and leave. Like the thymus, it only has efferent lymph vessels, which
leave from the hilium, and it does not have afferent lymph.
■ here two main types of tissue in the spleen are specialized for its two main functions:
■ White pulp contains lymphoid aggregations, mostly lymphocytes, and macrophages
which are arranged around the arteries. The lymphocytes are both T (mainly T-helper)
and B-cells.
■ Red pulp is vascular, and has parencyhma and lots of vascular sinuses. These are
sinusoids - a specialized type of capillary, which is very leaky.
■ Specifically, the white pulp encompasses several areas with distinct functions:

■ Branches of the splenic artery course through the capsule and

trabeculae of the spleen and then enter the white pulp. Within
the white pulp, the branch of the splenic artery is called the
central artery. Lymphocytes that aggregate around the central
artery constitute the periarterial lymphatic sheath (PALS). The
PALS has a roughly cylindrical configuration that conforms to the
course of the central artery. In cross sections, the PALS appears
circular and may resemble a lymphatic nodule. The presence of
the central artery, however, distinguishes the PALS from typical
lymphatic nodules found in other sites.
■ Nodules appear as localized expansions of the PALS and
displace the central artery so that it occupies an eccentric rather
than a central position.
■ The nodules are the territory of B lymphocytes; other
lymphocytes of the PALS are chiefly T lymphocytes that surround
the nodules. Thus, the PALS may be considered a thymus-
dependent zone similar to the deep cortex of a lymph node. The
nodules usually contain germinal centers, which, as in other
lymphatic tissues, develop as B cells proliferate after their
activation. In humans, germinal centers develop within 24 hours
after antigen exposure and may become extremely large and
visible with the naked eye. These enlarged nodules are called
splenic nodules or Malpighian corpuscles (not to be confused
with the renal corpuscles that have the same name).
Red pulp
■ composed of connective tissue known also as the cords of Billroth and many splenic
sinuses that are engorged with blood, giving it a red color. Its primary function is to filter the
blood of antigens, microorganisms, and defective or worn-out red blood cells
■ It consists of splenic sinuses separated by splenic cords (cords of Billroth)
■ Splenic cords consist of bunch of reticular fibers, cells, dendritic cells, macrophages,
lymphocytes, etc. Megakaryocytes are only present in fetal life, here.
■ The sinusoids here are discontinuous
■ The spleen is made of red pulp and white pulp, separated by the marginal zone; 76-79% of a
normal spleen is red pulp.
• Splenic artery enters at hilum and
branches as trabecular arteries,
which go into the white pulp to
become central artery.
• Lymphatic tissue surrounding the
central artery known as PALS
• Central artery passes through the
white pulp and give s 2 routes:
a)marginal sinuses b) those that
supply red pulp
• Central artery becomes penicillar
arterioles in the red pulp. The
branches of those are called
terminal arterial capilliaries

• Those open into sheathed capillaries

of cords. And thein veins
■ Branches of the splenic artery enter the white pulp from the trabeculae. The central artery
sends branches to the white pulp itself and to the sinuses at the perimeter of the white pulp,
marginal sinuses.
■ Central artery continues into the red pulp, where it branches into several straight arterioles
called penicillar arterioles.
■ The penicillar then continue as arterial capillaries.
■ Some arterial capillaries are surrounded by macrophages, and thus known as sheathed
capillaries. They empty into reticular meshwork of cords, rather than emptying into sinuses.
Blood entering has to be exposed first to the macrophages in the cords before squeezing
through the wall of sinus. This type of circulation is known as open circulation. Humans have
open circulation.
Antigen presenting cells in the spleen

■ Macrophages,
■ Dendritic cells
■ B cells