HISTOLOGY OF THE LYMPHOID SYSTEM
Monday, 11 October 2021
LYMPH NODE
2:08 pm
• covered by a capsule consisting of a layer of
connective tissue, which extends into the substance
of the node to form trabeculae.
• three regions:
○ Cortex
▪ composed of a row of lymphatic nodules;
▪ majority are secondary nodules with
germinal centers.
▪ Occasionally, primary nodules (without
germinal centers) may be found in the
cortex region
○ Paracortex
▪ lies between the cortex and medulla;
▪ most T cells reside in this region.
▪ HEVs are located in paracortex
□ sites where circulating lymphocytes
enter the node
○ medulla.
▪ composed of medullary cords and
medullary sinuses.
• Lymph enters the lymph node through afferent
lymphatic vessels;
○ courses through the subcapsular, peritrabecular,
A representation of types of lymphocytes.
and medullary sinuses;
3 major cell types in the immune system
○ exits the lymph node through the efferent
• Each of these cells originates from precursor cells in the bone marrow.
lymphatic vessel (follow the dotted magenta
• B and T lymphocytes are the main cell types located in lymphoid organs.
line).
○ B lymphocytes (B cells)
• The artery and vein enter and exit by passing through
the hilum of the lymph node.
▪ mature and become naive (virgin) B cells (immunocompetent cells that have not been previously exposed to foreign
antigen) in the bone marrow;
Lymph nodes
▪ they migrate to secondary lymph organs and may meet with antigens.
• bean shaped
▪ B cells that become activated by exposure to antigens (bacteria/viruses) differentiate into memory B cells and effector
• only lymphoid organs that have afferent lymphatic
B cells (plasma cells).
vessels
○ T lymphocytes (T cells)
• Regions
▪ differentiate from pro–T lymphocytes, which have migrated from the bone marrow into the thymus through the
○ cortex
circulatory system
▪ peripheral region of the lymph node and
▪ Thymocytes (developing lymphocytes) differentiate to naive (virgin) T cells in the thymus and then migrate to
▪ consists of a row of nodules.
secondary lymphoid organs where they may be activated by exposure to foreign antigens.
○ medulla
▪ Activated T cells can differentiate into both memory T cells and effector T cells.
▪ stains lighter and is located at the center
□ Effector T cells include helper T cells, cytotoxic T cells, and regulatory (suppressor) T cells.
area;
○ null cells
▪ composed of medullary sinuses and
medullary cord
B cells vs T Cells
○ paracortex
○ B and T cells share some common features.
▪ lies between the cortex and the medulla.
○ Each B and T cell is programmed to respond to a particular antigenic determinant.
• major sites to filter incoming lymph and are the sites
○ Each naive B cell or T cell is relatively short lived unless it becomes activated by contact with the antigen it recognizes.
for lymphocytes to meet antigens.
▪ If the T or B cells do not interact with an antigen, they will die; bc they are of no use
○ Both types give rise to both memory cells and effector cells if they interact with an antigen (“antigen dependent”).
○ Both B and T cells reside in specific regions in secondary lymphoid organs.
Lymph node (cross section)
The lymphoid system
• composed of
○ Lymphocytes
○ lymphoid organs
▪ Most lymphoid organs contain lymphatic nodules or diffuse lymphatic tissues
▪ play an important role in providing sites for lymphocytes to come into contact with antigens;
□ promote proliferation and maturation of lymphocytes;
□ promote B lymphocytes to become plasma cells, which produce antibodies.
▪ Lymphoid organs can be divided into two groups:
□ Primary lymphoid organs
 also called central lymphoid organs
 sites where lymphocytes differentiate and develop the ability to recognize foreign antigens and distinguish
nonself from self.
 include the bone marrow for B lymphocytes and the thymus for T lymphocytes.
□ Secondary lymphoid organs
 also called peripheral lymphoid organs
 are where mature lymphocytes (both B and T cells) encounter foreign antigens and the immune response
takes place.
 include MALT, lymph nodes, and the spleen.
○ lymphatic vessels.
germinal center
• composed of activated B cells in various stages of
maturation.
○ Cell size and nuclear shape are varied.
• large immature cells with round nucleus and
dispersed euchromatin are lymphoblasts and
plasmablasts.
○ differentiate into memory B cells and plasma
cells.
• also contains follicular dendritic (antigen-presenting)
cells, which help pass antigens to B cells.
medullary sinus
• surrounded by a medullary cord is shown here.
• carry lymph to where antigens are removed by
macrophages from slow-flowing lymph.
medullary cords
• contain B cells, plasma cells, dendritic cells, and
macrophages held within a network of reticular fibers.
Blasts-bigger cells compared to mature lymphocytes
A representation of B-lymphocyte maturation
• B lymphocytes (B cells) originate and mature in the bone marrow.
• Because naive (virgin) B lymphocytes differentiate from precursor cells (pro–B lymphocytes), they become randomly
programmed to recognize a specific antigenic determinant.
• Naive B lymphocytes are immunocompetent cells with specific antibodies (Igs) inserted into their plasma membrane as
receptors.
○ Each B lymphocyte has the ability to recognize and respond to a particular antigen.
○ apecific
○ After newly matured B lymphocytes leave the bone marrow, they use the vasculature and their own motility to recirculate
through the peripheral lymphoid organs (lymph nodes, spleen, MALT, etc.).
○ This continual wandering increases the likelihood that a lymphocyte will encounter its antigen if the antigen has gained
entry into the body.
• Naive B cells die in a few days or weeks if they do not meet their antigen, but those that encounter their specific antigen under
favorable conditions will become activated.
○ B cells that are activated by an encounter with antigens undergo cell division and differentiation.
▪ antigens (Allergens, viruses, bacteria, parasites)
▪ Each lymphocyte have receptor sites for certain antigens
□ When the lymphocytes first encounters the antigen, they will produce cells that will form memory cells
 These cells stay for a long time (depending on immunity)
▪ Once activated B cells becomes memory cells or plasma cells (effector cells)
□ Will be able to product eh antibodies which stay in the body for the second or third encounter; the body is
now prepared to attack these foreign materials
□ Memory cells can become antibodies (IgG, IgA, IgE, IgM, IgD)
Macrophages and lymphocytes are located in the lumen
(space of the medullary sinus
Medullary sinuses and cords, lymph node
HEVs(high endothelial venules)
• Found in the paracortex of the lymph node
• can be found in all of the secondary lymphoid organs
except the spleen.
• major sites for both naïve (inactivated) B and T
lymphocytes that have migrated from circulation into
the lymphatic tissue.
• After they enter the lymph node, B cells migrate to the
cortex region where they differentiate in the germinal
center.
○ Most T cells remain in the paracortex region
where they interact with antigen-presenting cells
(macrophages).
○ Once T cells acquire antigens, they release
cytokine (interleukins; IL-4, IL-5, and IL-6),
which stimulates B cells’ division and maturation
to become memory B cells and plasma cells
with the consequent production of antibodies
• Endothelial cells of HEVs are cuboidal cells and have
large round or oval nuclei with pale chromatin.
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with the consequent production of antibodies
• Endothelial cells of HEVs are cuboidal cells and have
large round or oval nuclei with pale chromatin.
A representation of helper T-cell and cytotoxic T-cell maturation markers.
• Each T lymphocyte has in its plasmalemma numerous TCRs, each with the same antigen recognition site.
• Each T cell also has either CD4 or CD8 molecules that act as essential coreceptors with the TCR.
○ (cell differentiation) = CD
○ There are so many types of CD because it will depend on the antigen they come into contact with
○ Specific for different types of antigens
○ produce more types so long as there are many more types of antigens that they come into contact with
• In the early stages of T-cell development, each thymocyte has both CD4+ and CD8+ markers, and mature T cells have either
CD4 or CD8 markers, but not both.
○ CD8+ cells have the capacity to recognize and react to their specific antigen only if it is presented by another cell in
association with MHC class I.
○ Another cell that will present part of the antigen to the T-cells is the antigen-presenting cell
▪ Function of the macrophage
○ Cytotoxic T cells have the CD8 while the T helper cells have the CD4
• Interaction between a cells which has been infected by a virus
○ Once a cytotoxic T cell recognizes a nonself antigen, it releases perforins and enzymes from granules to kill the infected
White dash-HEV
cells as well as some tumor cells, grafted cells, and virus-infected cells.
Yellow - Active macrophages
○ Once there is contact, there will now be the release of substances called perforins in order to transfer the perforins into the
cell
Hodgkin
Lymphoma
▪ So that the infected cell (with the virus) will not be able to proliferate and produce more viruses
• also known as Hodgkin disease
• one of the two major categories of malignant
lymphoid cancers
• characterized by painless enlargement of lymph
nodes, spleen, and liver.
• Patients often experience fever, night sweats,
unexpected weight loss, and fatigue.
• The cancer cells are transformed from normal
lymphoid cells, which reside predominantly in
lymphoid tissues.
• Characteristic Reed-Sternberg cells, of B cell origin,
can be found in affected lymphoid tissues.
○ These cells are large (20–50 μm) and contain
abundant, amphophilic, and finely
granular/homogeneous cytoplasm with two
mirror-image nuclei (“owl’s eyes”),
▪ each with an eosinophilic nucleolus and a
thick nuclear membrane.
• Radiotherapy and chemotherapy are both effective in
treatment of Hodgkin lymphoma.
○ The 5-year survival rate is approximately 90%
when the disease is detected and treated early.
THYMUS
HIV INFECTION
• Retrovirus
• Lead to AIDS (acquired immunodeficiency syndrome)
• May be transferred via Body fluids
○ Blood
○ Semen
○ breast milk.
• It is associated with a progressive decline in CD4+ T
cell numbers.(Low levels of CD4+ T cells)
○ Direct killing of CD4+ cells by the HIV virus
○ Increased rate of apoptosis in infected CD4+ T
cells
○ CD8+ cytotoxic lymphocytes recognizing &
killing CD4+ T cells after the virus has infected
them.
• The stage of infection can be determined by
○ measuring the patient’s CD4+ T cell number
○ level of HIV in the blood.
• HIV primarily infects
○ CD4+ helper T cells
○ Macrophages
○ dendritic cells (antigen-presenting cells).
• enters macrophages (CD4+ T cells as well),
replicates in the host cells, and the new viruses are
released from the host cells.
○ Greatly reduced numbers of CD4+ T cells result
in the loss of cell-mediated immunity
○ Without stimulation from CD4+ T helper cells,
humoral immunity function is compromised.
• AIDS patients are vulnerable to opportunistic
infections; common diseases include
○ Pneumocystis jiroveci
○ Toxoplasma spp
○ Candida albicans (Causes oral thursh)
• Histologically, lymph nodes in the early stage of HIV
infection reveal large, irregular lymphatic nodules and
an increased number of macrophages in the germinal
centers
MALT
• refers to diffuse lymphatic tissues or aggregate
lymphatic nodules in the mucosa of the digestive,
respiratory, and genitourinary tracts.
• Tonsils are composed of aggregate lymphatic
nodules and belong to MALT.
○ include pharyngeal, palatine, and lingual tonsils.
pharyngeal tonsil
• Located on Roof of the nasopharynx
• has epithelial invaginations, but no crypts, and is
covered by pseudostratified columnar epithelium
○ Traps bacteria and viruses
○ one of the lymphoid organs that provides an
environment for lymphocytes to meet antigens
▪ Battle ground where the T cells will have
to meet the foreign materials
• mostly consists of secondary nodules and a few
primary nodules.
○ A secondary nodule is composed of a germinal
center and mantle zone.
PHARYNGEAL TONSIL
Activated B cells
inactivated B cell
○ found mainly in the
germinal centers of
secondary nodules
○ primarily in primary
nodules.
Palatine tonsils
• paired
• located in the posterior and lateral portions of the oral
cavity.
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• primary lymphoid organ for T cells where T-cell
maturation takes place
• large in children and gradually atrophies to be
replaced by fat after puberty.
• located in the superior mediastinum and is divided
into smaller units called lobules by connective tissue
septae(septum), which extend inward from the
surface of the organ.
○ Lobules connected by septae
• does not have lymphatic nodules;
○ it is organized into cortex (peripheral) and
medulla (center).
• no afferent lymphatic vessels; its efferent lymphatic
vessels arise from the corticomedullary junction and
medulla and leave the thymus in company with the
blood vessels.
• Thymocytes (developing T cells) are concentrated in
the cortex region, and as they undergo differentiation,
they move down to the medulla.
THYMUS CORTEX
• contains thymocytes, macrophages, dendritic cells,
and epithelial reticular cells.
• macrophages and dendritic cells are antigenpresenting cells;
○ they present self-antigens to thymocytes for
recognition so that the macrophages will not be
misguided by foreign antigens and self
antigens .
• Only 1% to 2% of thymocytes survive and continue to
develop.
• Epithelial reticular cells are derived from endoderm
(lymphocytes are derived from mesoderm).
○ interconnected with each other to form a
framework to hold T lymphocytes together.
○ have large, ovoid nuclei and long processes and
make contact with each other by desmosomes.
○ contain secretory granules and produce
thymosin, serum thymic factor, and thymopoietin
hormone.
▪ These hormones play an important role in
T-cell maturation.
○ classified into six types based on their functions
and locations.
▪ Types I to III are located in the cortex
region
▪ type IV in the corticomedullary junction.
▪ Types V and VI are located in the medulla
of the thymus.
THYMUS - MEDULLA
• contains
○ naive (virgin) T cells
▪ immunocompetent cells
▪ mature from thymocytes in the cortex and
migrate from the medulla to secondary
organs where they become effective or
memory T cells if they meet with specific
foreign antigen
○ macrophages,
○ types V and VI epithelial reticular cells.
▪ located in the medulla
▪ type VI epithelial reticular cells show
various degrees of keratinization and are
arranged into concentric layers forming a
spherical structure called a Hassall
corpuscle
• place where T cells are selectively removed by
macrophages.
• HASSALL CORPUSCLE(S)
○ function of Hassall corpuscles is not fully
understood
○ Used to distinguish the thymus from other
lymphatic organs during the histological slide
examination.
○ More found in older individuals
SPLEEN
• large lymphoid organ (about 140–180 g in humans)
• located in the left superior quadrant of the abdomen
germinal centers of
secondary nodules
○ More found in older individuals
nodules.
Palatine tonsils
• paired
• located in the posterior and lateral portions of the oral
cavity.
○ have 10 to 20 crypts
○ The portion facing the oral cavity is covered by
stratified squamous epithelium.
• The nodules usually lie as a row beneath the
epithelium and surround each crypt.
▪ safeguard the entrance of the respiratory and
digestive tracts against microbe invasion.
▪ function in the recirculation of lymphocytes and
provide sites for the lymphocyte to interact with
antigens.
▪ Site of interaction – lymphocytes with antigens
• Zones
○ germinal center of a nodule
▪ contains large-sized B cells and antigenpresenting cells where B cells encounter
antigens and continue to proliferate and
develop into plasma cells.
PALATINE TONSIL
○ mantle zone of the nodule
▪ contains mostly small inactive B cells.
○ peripheral region of the nodule
▪ contains mostly T cells
• common sites for infection, such as acute tonsillitis,
recurrent tonsillitis, or tonsillar hypertrophy due to
lymphoid hyperplasia.
○ Tonsillectomy may be a choice in some children
with recurrent tonsillitis.
SPLEEN
• large lymphoid organ (about 140–180 g in humans)
• located in the left superior quadrant of the abdomen
• covered by a thick, dense connective tissue
(capsule), which extends into the organ to form
trabeculae.
○ Trabeculae
▪ Inner layer
▪ provide structural support for arteries and
veins, which supply the compartments
(white and red pulp) of the spleen.
• not organized into a cortex and medulla as are lymph
nodes and the thymus but is divided into
○ white pulp
▪ associated with a central artery
red pulp
▪ associated with a vein and venous
sinusoids.
• Functions of the spleen include
a. immune component (white pulp) to activate
Parts
lymphocytes and promote antibody production
• CAPSULE
by plasma cells
• TRABECULAE
b. filtration of blood and destruction of aged
• WHITE PULP
erythrocytes in red pulp
• RED PULP
c. serving as reservoir for erythrocytes and
platelets.
WHITE PULP
• composed of a
○ Central artery
○ PALS (periarteriolar lymphoid sheaths or
periarterial lymphatic sheaths)
▪ Periarteriolar lymphoid sheaths (or
periarterial lymphatic sheaths, or PALS)
are a portion of the white pulp of the
spleen. They are populated largely by T
cells and surround central arteries within
the spleen; the PALS T-cells are
presented with blood borne antigens via
myeloid dendritic cells.
○ Lymphatic nodule
• mantle zone
○ dark ring region around the germinal center
○ where small inactive B cells are hosted.
○ stains dark because of densely packed
lymphocytes.
• marginal zone
○ region that surrounds the white pulp
○ contains marginal sinuses
secondary nodules (follicles)
Appendix
• small, blind tube that extends from the cecum in the
lower right quadrant of the abdomen.
• contains large numbers of lymphatic nodules in its
lamina propria.
○ Most of the nodules are secondary nodules with
germinal centers.
▪ secondary nodules often penetrate into the
submucosa.
• Appendicitis
○ common disease
○ triggered by bacterial and viral infections
resulting in hyperplasia of lymphatic nodules
and obstruction of the lumen of the appendix.
○ Symptoms
▪ abdominal pain, which most likely will be
localized at the McBurney point (one third
of the distance between the anterior
superior iliac spine and the umbilicus on
the right side) as the disease progresses.
APPENDIX (cross section) -MALT
▪ Fever
▪ Nausea
▪ Vomiting
○ Emergency appendectomy is the first treatment
choice for most cases.
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primary nodules
• nodules with germinal
• nodules without the
centers
germinal centers
• where B cells actively
• contain most of the
differentiate into large cells
inactive B cells
(lymphoblasts and
lymphocytes).
RED PULP
• red because it is rich in blood (Filled with blood)
• Reservoir for platelets
• stains light and contains splenic cords and venous
sinuses that are filled with blood
• Splenic cords
○ B cell, T cell, plasma cells, macrophages, etc
▪ Macrophages in the splenic cord often
extend their processes into the lumen of
the sinuses to reach and engulf foreign
substances, microbes, and aged
erythrocytes
• Venous sinuses
○ Made of discontinuous capillaries
▪ have large lumens
▪ incomplete basal laminae
▪ gaps between endothelial cells
○ Allow blood cells to pass through the capillary
wall
G, germinal center