Cui Dongmei. Atlas of Histology: with functional and clinical correlations. 1st ed

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Figure 10-4A. A representation of T-lymphocyte maturation. H&E, 19 (thymus); 200 (spleen)

T cells are derived from pro–T lymphocytes, which migrate from the bone marrow to the thymus where they undergo cell division to generate

a large number of developing lymphocytes (thymocytes). As thymocytes undergo the differentiation process, they begin to express TCR and

other cell-surface proteins. Some of the maturation markers of T cells help them to recognize and interact with MHC molecules. In order to

survive and mature, thymocytes must negotiate both positive and negative selection processes. Positive selection involves promoting survival

of only those thymocytes that are able to interact at an appropriate level with self-MHC molecules, a capacity essential to their ability to

mount effective immune responses. Negative selection involves destruction of thymocytes that have too strong an interaction with self-MHC

molecules; these cells have the potential to contribute to autoimmune disease, and they are removed by macrophages. Positive selection occurs

in the cortex of the thymus and negative selection mainly in the medulla. It has been estimated that only 1% to 2% of thymocytes survive

these selection processes and complete differentiation to become immunocompetent T cells (naive T cells). Naive T cells leave the medulla

of the thymus through the circulation and migrate to the speciﬁ c regions of the secondary lymphoid organs where they may encounter the

foreign antigen that they are programmed to recognize. If antigen stimulation occurs, virgin T cells become active, undergo cell division, and

give rise to clones composed of both memory T cells and effector T cells. Memory T cells can be found in the paracortex of the lymph nodes

and may migrate to inﬂ ammatory sites and give rise to effector T cells. Effector cells include helper T cells, cytotoxic T cells, and regulatory (sup-

pressor) T cells. Each effector cell has either CD4 or CD8 as a surface marker. Effector cells participate in cell-mediated immune responses.

Figure 10-4B. 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. 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

speciﬁ c antigen only if it is presented by another cell in association with MHC class I. All nucleated cells of the body express MHC class I

and present fragments of internally synthesized peptides on their surface MHC class I molecules. If any cell in the body becomes infected

by a virus and synthesizes viral proteins, fragments of these viral proteins are presented as foreign antigens by the cell’s surface MHC class I

molecules. If such a virus-infected cell is encountered by a cytotoxic T cell (CD8

cells) that bears TCRs that recognize one of the viral antigens,

the cytotoxic T cell will become activated and destroy the virus-infected cell. CD4

cells recognize their speciﬁ c antigen only if it is presented

by another cell in association with MHC class II. MHC class II is expressed by antigen-presenting cells. If an antigen-presenting cell presents

antigen to a CD4

(helper T cell) that recognizes the antigen, the helper T cell will become activated to provide signals that promote activation

of other lymphocytes. The illustration on the left shows helper T cells with TCR and surface marker CD4. TCR is an antigen receptor that

is speciﬁ c to the peptide that is attached to the groove of the MHC II molecule on the macrophage. This peptide presents a foreign antigen

to helper T cells. The illustration on the right shows TCR and CD8 markers on the cytotoxic T cells’ surface. TCR of the cytotoxic T cell

responds to antigen presented in association with MHC I molecules of the infected cells. Once a cytotoxic T cell recognizes a nonself antigen,

it releases perforins and enzymes from granules to kill the infected cells as well as some tumor cells, grafted cells, and virus-infected cells.

MHC I

Cytotoxic T cells

CD8

TCR

Virus-infected cell

MHC II

Peptide

Helper T cells

CD4

TCR

Antigen-presenting cell

(macrophage)

Perforins

Circulation

PALS

Pro–T lymphocytes

in bone marrow

Pro–T lymphocytes develop

into lymphoblasts in thymus

Migrate to T–cell regions

(example of PALS in spleen)

Memory T Cell

(CD 4 and CD 8 cells)

Pro–T lymphocytes

CD8

CD4

TCR

Cytotoxic

T cells

Virgin/naive T cells

(medulla)

Activated effector T cells

Helper

T cells

Regulatory

(suppressor) T cells

Thymocytes

(cortex)

Thymocytes

(cortex)

Pro–T lymphocytes

T Lymphocytes

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Figure 10-5A. A representation of helper T-lymphocyte activation.

The CD4 surface marker on a helper T cell recognizes MHC II surface proteins on the antigen-presenting cell. The TCR binds with the

peptide-MHC complex on the surface of the macrophage (or other types of antigen-presenting cells); therefore, antigens are presented

to helper T cells. The activating signals (secreted proteins, cytokines) are exchanged between the helper T cells and the macrophages.

There are two main types of helper T cells: (1) Activated helper (T

2) cells release a variety of interleukins/cytokines that stimulate

B cells to proliferate and increase the population of plasma cells, thereby increasing production of antibodies. (2) Activated helper

1) cells release and bind with IL-2, stimulating proliferation and activation of T

1 cells and greatly increasing their own numbers.

Activated T

1 cells provide signals that promote proliferation of cytotoxic T cells (CD8

cells) and activation of macrophages. In turn,

activated macrophages kill bacteria by a variety of mechanisms (see Fig. 8-6) and stimulate additional inﬂ ammatory processes.

MHC II

Antigen

(1) Helper (T 2) cells

(2) Helper (T 1) cells

B cells

T 1 cells

Plasma cell Antibodies

CD4

TCR

IL-2

IL-4, IL-5, IL-6

IFN-„

Antigen-presenting

cell (macrophage)

Antigen-presenting

cell (macrophage)

Activated macrophage

(kill bacteria)

CLINICAL CORRELATION

Figure 10-5B.

Human Immunodeﬁ ciency V

irus Infection.

Infection by the retrovirus HIV leads to acquired immunodeﬁ ciency

syndrome (AIDS). Infection may be transferred from an infected indi-

vidual through exposure to body ﬂ uids including blood, semen, and

breast milk. It is associated with a progressive decline in CD4

T cell

numbers. The stage of infection can be determined by measuring the

patient’s CD4

T cell number and the level of HIV in the blood. HIV

primarily infects CD4

helper T cells, macrophages, and dendritic cells

(antigen-presenting cells). The low level of CD4

T cells in the blood

of HIV-infected patients may be because of (1) the HIV virus killing

infected CD4

T cells directly, (2) increased rates of apoptosis in infected

CD4

T cells, or (3) CD8

cytotoxic lymphocytes recognizing and kill-

ing CD4

T cells after the virus has infected them. The HIV virus 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 pneumonia, toxoplas-

mosis, and thrush. 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 (Fig. 10-9C).

Perforins

CD4

TCR

Helper

T cells

Infected

macrophage

Macrophage

HIV

CD8

TCR

Cytotoxic T cells

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Figure 10-6. Overview of the lymphoid organs.

Locations of the principal lymphoid organs and vessels are shown on the left; the route of lymph drainage is shown on the right.

Structures of the Lymphoid Tissues and Organs

Thoracic

duct

Subclavian

vein

Right lymphatic duct

Peyer

patches

(ileum)

Appendix

Bone marrow

Palatine

tonsil

Lymph node

(inguinal node)

Lymph node

(popliteal node)

Lymph node

(axillary node)

Thoracic duct

Lymphatic vessel

Thymus

Lymph node

(cervical node)

Spleen

Pharyngeal

tonsil

Lymph

Lymphatic capillaries

Lymphatic vessels

Lymph nodes

Lymphoid

organs

Lymphatic

tissue

Lymphatic vessels

Afferent lymphatic vessels

Efferent lymphatic vessels

Right lymphatic duct

Subclavian veins

Thoracic duct (left)

I. Mucosa-associated lymphoid tissue

A. Gut-associated lymphoid tissue: Lymphatic tissue in the

mucosa of the digestive tract, such as Peyer patches in

ileum and nodules in the appendix.

B. Bronchus-associated lymphoid tissue: Lymphatic tissue

in the mucosa of the respiratory tract, such as lymphatic

tissue in bronchi, bronchioles.

C. Tonsils

1. Palatine tonsils

2. Pharyngeal tonsils

3. Lingual tonsils

II. Lymphoid organs

A. Bone marrow (see Chapter 9, “Circulatory System”)

B. Thymus

1. Cortex

2. Medulla

C. Lymph nodes

1. Afferent lymphatic vessels

2. Efferent lymphatic vessels

3. Cortex

4. Paracortex

5. Medulla

D. Spleen

1. White pulp

2. Red pulp

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Figure 10-7. Orientation of detailed lymphoid organ illustrations.

Structures of Lymphoid Organs with Figure Numbers

Fig. 10-14A,B,C

Fig. 10-15A,B

Fig. 10-16

Fig. 10-8B

Fig. 10-8A

Fig. 10-10

Fig.10-11 A,B,C,D

Fig. 10-12 A,B

Fig. 10-13A,B,C

Fig. 10-9A

Pharyngeal tonsil

Figure 10-8A

Palatine tonsil

Figure 10-8B

Appendix

Figure 10-9A

Lymph node

Figure 10-9B

Figure 10-9C

Figure 10-10

Figure 10-11A

Figure 10-11B

Figure 10-11C

Figure 10-11D

Figure 10-12A

Figure 10-12B

Figure 10-12C

Thymus

Figure 10-13A

Figure 10-13B

Figure 10-13C

Spleen

Figure 10-14A

Figure 10-14B

Figure 10-14C

Figure 10-15A

Figure 10-15B

Figure 10-16

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Mucosa-Associated Lymphoid Tissue

Name Location Epithelial

Covering

Crypts Capsule Lymphatic

Nodules (Follicles)

Palatine tonsils (2) Posterolateral walls

of the oral cavity

Stratiﬁ ed squamous

epithelium

(nonkeratinized)

Yes, deep and

branched crypts

divide tonsil into

lobules

Thick, incomplete

connective tissue

capsule; par-

tially covered by

epithelium

Each lobule contains

numerous lymphatic

nodules, most having

a germinal center

Pharyngeal

(adenoid) tonsil (1)

Posterior roof of the

nasopharynx

Pseudostratiﬁ ed

ciliated columnar

epithelium

No, only epithelial

invagination

Thin, incomplete

connective capsule;

partially covered

by epithelium

Mostly diffuse

lymphoid tissues

and some lymphatic

nodules

Lingual tonsils (2) Posterior ﬂ oor of the

mouth (surface of

the posterior third of

the tongue)

Stratiﬁ ed squamous

epithelium

(nonkeratinized)

Yes, wide

nonbranched crypt;

duct of mucous

gland opens into

the crypt

No capsule;

partially covered

by epithelium

Rows of lymphatic

nodules supported

by connective tissue

septa

TABLE 10-1 Tonsils

Figure 10-8A. Pharyngeal tonsil, MALT. H&E, 76; inset 184

MALT refers to diffuse lymphatic tissues or aggregate lymphatic nod-

ules in the mucosa of the digestive, respiratory, and genitourinary

tracts. Comparable tissue is GALT in the gut and BALT in the respi-

ratory system. Tonsils are composed of aggregate lymphatic nodules

and belong to MALT. Tonsils include pharyngeal, palatine, and lingual

tonsils. The pharyngeal tonsil is located in the roof of the nasophar-

ynx (Fig. 10-6). It has epithelial invaginations, but no crypts, and is

covered by pseudostratiﬁ ed columnar epithelium. The pharyngeal ton-

sil traps bacteria and viruses and is one of the lymphoid organs that

provides an environment for lymphocytes to meet antigens. It mostly

consists of secondary nodules and a few primary nodules. A secondary

nodule is composed of a germinal center and mantle zone. Activated

B cells are found mainly in the germinal centers of secondary nodules

and inactivated B cells primarily in primary nodules.

Pseudostratified

columnar

epithelium

Pseudostratified

columnar

epithelium

Pseudostratified

columnar

epithelium

Mantle

zone

Primary

nodule

Germinal

center

Pseudostratified

columnar

epithelium

Mantle

zone

Primary

nodule

Germinal

center

Pseudostratified

columnar

epithelium

Pseudostratified

columnar

epithelium

Germinal

center

Large lymphocytes

in germinal center

Mantle

zone

Mantle

zone

Stratified squamous

epithelium

Germinal

center

Large lymphocytes

in germinal center

tifie

ith

liu

Stratified squamous

epithelium

Stratified squamous

ithelium

Figure 10-8B. Palatine tonsil, MALT. H&E, 83; inset 750

(left); 197 (right)

Palatine tonsils are paired and are located in the posterior and lateral

portions of the oral cavity. They have 10 to 20 crypts and the portion

facing the oral cavity is covered by stratiﬁ ed squamous epithelium.

The nodules usually lie as a row beneath the epithelium and sur-

round each crypt. They safeguard the entrance of the respiratory and

digestive tracts against microbe invasion. They also function in the

recirculation of lymphocytes and provide sites for the lymphocyte

to interact with antigens. The germinal center of a nodule contains

large-sized B cells and antigen-presenting cells where B cells encoun-

ter antigens and continue to proliferate and develop into plasma

cells. The mantle zone of the nodule contains mostly small inactive

B cells. The peripheral region of the nodule contains mostly T cells.

Palatine tonsils are common sites for infection, such as acute tonsil-

litis, recurrent tonsillitis, or tonsillar hypertrophy due to lymphoid

hyperplasia. Tonsillectomy may be a choice in some children with

recurrent tonsillitis.

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Figure 10-9A. Appendix, MALT. H&E, 18

The appendix and Peyer patches in the ileum of the digestive system

are GALT. The appendix is a small, blind tube that extends from

the cecum in the lower right quadrant of the abdomen. It contains

large numbers of lymphatic nodules in its lamina propria. Most

of the nodules are secondary nodules with germinal centers. The

secondary nodules often penetrate into the submucosa.

Lymphatic

nodules

CLINICAL CORRELATIONS

Figure 10-9B.

Diffuse Large B-Cell Lymphoma. H&E,

1,000

Diffuse large B-cell lymphoma (DLBCL) is the most

common type of non-Hodgkin lymphoma (25% of all

lymphomas), characterized by a fast-growing and often

symptomatic mass at a nodal or extranodal site. The

most common extranodal site is the gastrointestinal

tract, but other sites include skin, soft tissue, Waldeyer

ring, lung, spleen, and kidneys. Patients may experi-

ence fever, weight loss, and drenching night sweats.

Histologically, tumor cells are large with large nuclei,

open chromatin, and prominent nucleoli. The tumor

grows in a diffuse pattern. Treatment for DLBCL

includes intensive combination chemotherapy with

possible radiotherapy to the involved tumor site.

Figure 10-9C.

Lymph Node, HIV Infection. H&E, 40

HIV infection is associated with a progressive decline

in helper T lymphocytes, resulting in immunosuppres-

sion (Fig. 10-5B). Patients with acute HIV infection

may experience fever

, lymphadenopathy, pharyngitis,

rash, and myalgia. The chronic phase of HIV infection

may last from months to years with patients exhibiting

few symptoms. During the ﬁ nal crisis phase, patients

are at an increased risk of opportunistic infections and

neoplasms. Lymph nodes in the early stage of HIV

infection show marked follicular lymphoid hyperplasia

with enlarged, irregularly shaped follicles (lymphatic

nodules) and increased numbers of macrophages in

the germinal center. The enlarged lymph nodes may be

found ﬁ rst in the upper body, then around the lungs,

and ﬁ nally around the bowel. Patients with compro-

mised immunity are highly likely to be infected by

bacteria and other microbes. Anti-HIV drugs include

four major classes: Reverse transcriptase inhibitors,

protease inhibitors, entry and fusion inhibitors, and

integrase inhibitors.

Lymphoma cells

with large nucleolus

Large irregular

lymphoma cells

Enlarged and

irregular-shaped

lymphatic nodules

Lymphatic

nodules

Lymphatic

nodules

Appendicitis is a common disease, which may be triggered by

bacterial and viral infections resulting in hyperplasia of lymphatic

nodules and obstruction of the lumen of the appendix. Patients

may experience abdominal pain, which most likely will be local-

ized 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. Fever, nausea, and vomiting are the com-

mon symptoms. Emergency appendectomy is the ﬁ rst treatment

choice for most cases.

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191

SYNOPSIS 10-2 Lymphoid Organs

In ■ primary lymphatic organs, lymphocytes differentiate and mature; B cells’ primary lymphoid organ is bone marrow;

T cells’ primary lymphoid organ is the thymus.

■ secondary lymphatic organs, lymphocytes encounter and respond to foreign antigens; secondary lymphoid organs

include MALT, lymph nodes, and spleen.

Lymphatic nodules

■ are spherical structures that contain accumulated lymphocytes. They include primary nodules and

secondary nodules.

Primary nodules

■ contain mostly small (inactivated) B cells and do not have a germinal center.

Secondary nodules

■ contain mostly large (activated) B cells and have a germinal center (light area in the center).

Lymphatic nodules

■ contain mostly B cells.

The

■ thymus, paracortex of the lymph node, and PALS in the spleen contain mostly T cells.

Afferent

lymphatic vessels

Artery

Medullary

sinuses

Efferent

lymphatic vessel

Postcapillary venules

(HEV in paracortex)

Venules

Small vein (medulla)

Vein

Subcapsular

sinuses

Small artery

in medulla)

ranches of artery

Peritrabecular

sinuses

Arterioles

(paracortex and cortex)

capillaries

(nodules of cortex)

Vascular channels (blood):

Lymphatic channels (lymph):

Secondary

nodule

Afferent

lymphatic vessel

Subcapsular sinus

Primary

nodule

Medullary

cords

Medullary

sinuses

Efferent

lymphatic vessel

Trabecula

Germinal center

of secondary

nodule in cortex

HEV in

paracortex

Trabecula

Peritrabecular

sinus

Germinal center

of secondary

nodule in cortex

Medulla

Paracortex

Artery

Vein

Cortex

Capsule

Medulla

Paracortex

Para

cortex

Paracortex

Medulla

Paracortex

Figure 10-10. Overview of the lymph node.

This is a representation of a lymph node. It is covered by a capsule consisting of a layer of connective tissue, which extends into the

substance of the node to form trabeculae. The lymph node is divided into three regions: cortex, paracortex, and medulla. (1) The

cortex is composed of a row of lymphatic nodules; the majority are secondary nodules with germinal centers. Occasionally, primary

nodules (without germinal centers) may be found in the cortex region. (2) The paracortex lies between the cortex and medulla; most

T cells reside in this region. HEVs are located in paracortex and are the sites where circulating lymphocytes enter the node. (3) The

medulla is composed of medullary cords and medullary sinuses. Lymph enters the lymph node through afferent lymphatic vessels;

courses through the subcapsular, peritrabecular, and medullary sinuses; and exits the lymph node through the efferent lymphatic

vessel (follow the dotted magenta line). The artery and vein enter and exit by passing through the hilum of the lymph node.

Lymph Nodes

Comparison of Lymph and Blood Flow

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Organ Systems

Figure 10-11A. Lymph node. H&E, 43

Lymph nodes are bean shaped and are the only lymphoid

organs that have afferent lymphatic vessels (Fig. 10-9). This

is a cross section of a lymph node. (1) The cortex is the

peripheral region of the lymph node and consists of a row of

nodules. (2) The medulla stains lighter and is located at the

center area; it is composed of medullary sinuses and medul-

lary cords (Fig. 10-11B,D). (3) The paracortex lies between

the cortex and the medulla. Lymph nodes are the major sites

to ﬁ lter incoming lymph and are the sites for lymphocytes to

meet antigens.

Figure 10-11B. Lymph node. H&E, 100

The subcapsular sinus carries lymph from afferent lymphatic

vessels into the node by passing through peritrabecular sinuses

to the medullary sinuses. The nodules in the cortex consist of a

germinal center (loosely packed large B cells) and a mantle zone

(containing tightly packed small B cells). T cells mainly reside

in the paracortex region where they interact with antigen-

presenting cells; lymphocytes enter the lymph node through

HEVs in the paracortex region (Fig. 10-12A,B).

Figure 10-11C. Germinal center, lymph node. H&E, 658

The germinal center is composed of activated B cells in various

stages of maturation. Cell size and nuclear shape are varied.

The large immature cells with round nucleus and dispersed

euchromatin are lymphoblasts and plasmablasts. They dif-

ferentiate into memory B cells and plasma cells. The germinal

center also contains follicular dendritic (antigen-presenting)

cells, which help pass antigens to B cells. They are difﬁ cult to

recognize in H&E stain.

Figure 10-11D. Medullary sinuses and cords, lymph node.

H&E, 658

A medullary sinus surrounded by a medullary cord is shown

here. Medullary sinuses carry lymph to where antigens are

removed by macrophages from slow-ﬂ owing lymph. The

medullary cords contain B cells, plasma cells, dendritic cells,

and macrophages held within a network of reticular ﬁ bers.

Medullary cord

Medullary

cord

Medullary cord

Lumen of the

medullary sinus

Lumen of the

medullary sinus

Medullary

cord

Macrophages

Medullary cord

Lymphocytes in the

medullary sinus

Lymphocytes in the

medullary sinus

Lymphatic

nodules

lla

Medulla

Paracortex

Cortex

Subcapsular sinus

Peritrabecular

sinus

Peritrabecular

sinus

Medullary

cords

Medullary

cords

Germinal

center

Germinal

center

Medullary

sinuses

Medullary

sinuses

Medullary

sinuses

Medullary

sinuses

Paracortex

Mantle

zone

Mantle

zone

Lymphoblast

Small

lymphocytes

Small

lymphocytes

Lymphoblast

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193

CLINICAL CORRELATION

Figure 10-12C.

Hodgkin Lymphoma. H&E, 824

Hodgkin lymphoma, also known as Hodgkin disease,

is one of the two major categories of malignant lym-

phoid cancers, characterized by painless enlargement of

lymph nodes, spleen, and liver

. Patients often experi-

ence fever, night sweats, unexpected weight loss, and

fatigue. The cancer cells are transformed from normal

lymphoid cells, which reside predominantly in lym-

phoid tissues. Characteristic Reed-Sternberg cells, of

B cell origin, can be found in affected lymphoid tis-

sues. These cells are large (20–50 μm) and contain

abundant, amphophilic, and ﬁ nely granular/homoge-

neous 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.

Reed-Sternberg

cell

Lymphocyte

Figure 10-12A. High endothelial venules (HEVs), paracor-

tex of lymph node. H&E, 272; inset 720

Arteries that serve a lymph node enter the hilum and give rise

to branches that pass through the medulla and reach the cortex

where they form a network of capillaries in the nodule (fol-

licle) region. Postcapillary venules (in the paracortex region)

carry blood from the capillary bed back to the venule system

and out of the lymph node at the hilum (Fig. 10-10). HEVs

are specialized postcapillary veins, which are lined by cuboidal

cells instead of squamous endothelial cells. The apical surfaces

of these cuboidal cells contain rich glycoproteins that attract

lectinlike receptors (L selectin) on the surface of the lympho-

cytes, which helps lymphocytes stop and attach to the HEVs.

Lymphocytes pass through HEVs by way of diapedesis and

enter the lymph node from blood circulation. The inset shows

a lymphocyte escaping from a HEV into the lymphatic tissue.

Cubodial

cell

Lymphatic tissue

High

endothelial

venule

High

endothelial

venule

Lymphatic tissue

High

endothelial

venule

Cuboidal

cell

High

endothelial

venule

Active

macrophages

High

endothelial

venules

Active

macrophages

High

endothelial

venules

High endothelial

venule

High endothelial

venule

Active

macrophage

Active

macrophage

Figure 10-12B. High endothelial venules, paracortex of

lymph node. H&E, 281; insets 725

HEVs can be found in all of the secondary lymphoid organs

except the spleen. They are the major sites for both naive B and

T lymphocytes that have migrated from circulation into the lym-

phatic 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 inter-

act with antigen-presenting cells (macrophages). Once T cells

acquire antigens, they release cytokine (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 produc-

tion of antibodies (Fig. 10-5A). Endothelial cells of HEVs are

cuboidal cells and have large round or oval nuclei with pale

chromatin. The insets show a lymphocyte in the cross section

of a HEV (upper); and an active macrophage in the paracortex

region (lower).

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Organ Systems

Figure 10-13A. Thymus. H&E, 46

The thymus is a primary lymphoid organ for T cells where T-cell

maturation takes place. The thymus is large in children and gradu-

ally atrophies to be replaced by fat after puberty. The thymus is

located in the superior mediastinum and is divided into smaller

units called lobules by connective tissue septae, which extend

inward from the surface of the organ. The thymus does not have

lymphatic nodules; it is organized into cortex (peripheral) and

medulla (center). There are no afferent lymphatic vessels; its effer-

ent 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. The blood vessels pass through the interlobar septa

and enter the thymus at the junction of the cortex and medulla.

Thymic capillaries are continuous capillaries with thick basement

membranes. They are surrounded by epithelial reticular cells and

form an effective thymic-blood barrier, which prevents foreign

antigens from entering the thymus.

Septum

Medulla

Cortex

Medulla

Septum

Cortex

Medulla

rte

Medulla

Cortex

lla

Cortex

rte

Medulla

Cortex

Septum

Epithelial

reticular

cells

Epithelial reticular cells

Macrophage

Epithelial reticular cells

Epithelial

reticular

cells

Epithelial reticular cells

Macrophage

Figure 10-13B.

Thymus, cortex. H&E, 278; insets 510

The cortex region contains thymocytes, macrophages, dendritic

cells, and epithelial reticular cells. The macrophages and dendritic

cells are antigen-presenting cells; they present self-antigens to

thymocytes. Only 1% to 2% of thymocytes survive and continue to

develop. Epithelial reticular cells are derived from endoderm (lym-

phocytes are derived from mesoderm). They are interconnected with

each other to form a framework to hold T lymphocytes together.

They have large, ovoid nuclei and long processes and make contact

with each other by desmosomes. They contain secretory granules

and produce thymosin, serum thymic factor, and thymopoietin hor-

mone. These hormones play an important role in T-cell maturation.

The epithelial reticular cells can be classiﬁ ed into six types based on

their functions and locations. Types I to III are located in the cortex

region, and type IV in the corticomedullary junction. Types V and

VI are located in the medulla of the thymus.

Epithelial reticular cells

Hassell

corpuscle

Hassall

corpuscle

Figure 10-13C. Thymus, medulla. H&E, 624; insets 843

The medulla region contains naive (virgin) T cells, macrophages,

and types V and VI epithelial reticular cells. The naive T cells

are immunocompetent cells. They 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 speciﬁ c

foreign antigen. The medulla of the thymus is also the place where

T cells are selectively removed by macrophages. Both types V and

VI epithelial reticular cells are located in the medulla. The type

VI epithelial reticular cells show various degrees of keratinization

and are arranged into concentric layers forming a spherical struc-

ture called a Hassall corpuscle. Although the function of Hassall

corpuscles is not fully understood, their numbers are increased

in older individuals. Hassall corpuscles can be used as one of the

unique features to distinguish the thymus from other lymphatic

organs during the histological slide examination.

Thymus

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