Immune Cells & Lymphoid Organs

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*The answer is C.* T lymphocytes mature and become immunocompetent in the cortex of the thymus, whereas B lymphocytes do so in the bone marrow. After an antigenic challenge, lymphocytes proliferate and differentiate in various lymphoid tissues

In which of the following sites do lymphocytes become immunocompetent? (A) Germinal center of secondary lymphoid nodules (B) White pulp of the spleen (C) Thymic cortex (D) Red pulp of the spleen (E) Paracortex of lymph nodes

*The answer is E.* Splenic cords (of Billroth) are the sites in which abnormal RBCs are removed from circulation.

A 12-year-old African-American girl presents with anemia and a large percentage of her peripheral erythrocytes appear sickle-shaped. Genetic testing reveals homozygosity for sickle cell disease. In which of the following sites will the abnormal RBCs be removed from the circulation? a. Thymic cortex b. Periarteriolar lymphoid sheathes of splenic white pulp c. Medullary sinuses of lymph nodes d. Thymic medulla e. Splenic cords (of Billroth)

*The answer is A.* Most lymphocytes (about 90%) enter lymph nodes and diffuse/nodular lymphatic tissue through specialized postcapillary venules termed high endothelial venules (HEVs). HEVs are lined by cuboidal endothelial cells. They express an array of cell adhesion molecules (selectins and addressins) that mediate leukocyte binding and transendothelial migration (diabedesis). In lymph nodes, HEVs are located primarily in the deep cortex, a T-cell-rich region of the lymph node. Upon arrival in a lymph node, T cells meander in the deep cortex, while B cells migrate to the cortex. Immunohistochemical assays are used routinely to localize B- and T-cell populations in primary and secondary lymphoid organs. None of the other regions of the lymph node are characterized by the presence of HEVs.

A 22-year-old woman presents with a 3-day history of sore throat. Her temperature is 38.7°C (103°F). Physical examination reveals inflamed tonsils and swollen cervical lymph nodes. Trafficking of blood-borne lymphocytes to regional lymph nodes in this patient involves cell migration through high endothelial venules (HEVs). These specialized postcapillary venules are located primarily in which of the following regions of the patient's lymph nodes? (A) Deep cortex (B) Medullary sinus (C) Nodular cortex (D) Subcapsular sinus (E) Trabecular sinus

*The answer is A.* The oval identifies a region of the spleen that is filled with venous sinuses separated by thin cords. The splenic cords are difficult to visualize by light microscopy; they are composed of reticular cells and reticular fibers and may include a variety of acute and chronic inflammatory cells. Together, splenic cords and sinuses are referred to as red pulp. Circulation of blood through red pulp allows macrophages to remove senescent or defective RBCs and filter the blood for pathogens. None of the other choices describe histologic features of red pulp in the spleen.

A 26-year-old man ruptures his spleen in a motorcycle accident and requires an emergency splenectomy to control internal bleeding. The surgical specimen is examined in the pathology department (shown in the image). Which of the following histologic features best characterizes the region of the spleen indicated by the oval? (A) Cords and venous sinuses (red pulp) (B) Periarteriolar lymphoid sheath (PALS) (C) Splenic capsule and visceral peritoneum (D) Splenic lymphoid nodules (white pulp) (E) Trabecular connective tissue

*The answer is A.* Blood flow through the spleen is complex. In brief, the branches of splenic and trabecular arteries that enter the white pulp of the spleen are termed central arteries. Lymphocytes surround the central artery and its branches, forming a periarteriolar lymphatic sheath (PALS). The central artery continues into the red pulp of the spleen where it gives rise to multiple, small penicillar arterioles. These arterioles form sheathed capillaries that empty blood directly into splenic cords. The open circulation of blood in the spleen, from sheathed capillaries to splenic cords to venous sinuses, provides an opportunity for macrophages to remove senescent RBCs.

A 35-year-old woman with systemic lupus erythematosus undergoes a partial splenectomy to control her autoimmune hemolytic anemia. The surgical specimen is examined by a multiheaded microscope in the pathology department. For the surgical specimen described, identify the blood vessels indicated by the arrows. (A) Central (B) Cortical (C) Penicillar (D) Splenic (E) Trabecular

*The answer is A.* The double arrow identifies a secondary lymphoid nodule within the white pulp of the spleen. The germinal center is surrounded by a mantle of small lymphocytes. Red pulp immediately adjacent to the white pulp is referred to as the marginal zone. Th1 lymphocytes (choice D) interact with B cells and mediate delayed hypersensitivity reactions (e.g., poison ivy). Th2 lymphocytes (choice E) interact with eosinophils and mast cells, and mediate hypersensitivity responses to parasitic infestations and allergens. Although the other cells are found in diffuse and nodular lymphatic tissue, they do not form germinal centers in lymphoid follicles.

A 35-year-old woman with systemic lupus erythematosus undergoes a partial splenectomy to control her autoimmune hemolytic anemia. The surgical specimen is examined by a multiheaded microscope in the pathology department. Which of the following cells is expected to be most abundant in the region of the white pulp indicated by the double arrow (shown in the image)? (A) B lymphocytes (B) Dendritic cells (C) Macrophages (D) Th1 lymphocytes (E) Th2 lymphocytes

*The answer is D.* Examination of the photomicrograph reveals medullary cords within an open medullary sinus. A fine meshwork of reticular fibers and reticular cell processes crisscrosses this lymphatic sinus. As lymph filters through the lymph node, antigens and antigen-presenting cells provide signals to lymphocytes to coordinate their activation, proliferation, and maturation. Mature plasma cells leave the cortex of the node. They populate medullary cords and secrete antibodies. Antibodies (immunoglobulins) are subsequently delivered to the blood through the right lymphatic trunk or the left thoracic duct. Antibodies are targeting molecules that initiate humoral and/or cellular mechanisms of cytotoxicity. None of the other regions/structures exhibit histologic features of a medullary sinus.

A 55-year-old woman with breast cancer undergoes a modified radical mastectomy with axillary lymph node dissection. Another axillary lymph node obtained from the patient is examined in the pathology department. What is the appropriate name for the region indicated by the asterisk? (A) Cortical sinus (B) Efferent lymphatic vessel (C) Medullary cord (D) Medullary sinus (E) Trabecular sinus

*The answer is A.* Multiple afferent lymphatic vessels penetrate the capsule of lymph node. Lymph that is delivered to the subcapsular sinus flows through trabecular and medullary sinuses, before being drained by an efferent lymphatic vessel located at the hilum of the lymph node. The image shows an afferent lymphatic vessel located outside the capsule. None of the other structures exhibit the morphology of afferent lymphatic vessels near the periphery of a lymph node.

A 55-year-old woman with breast cancer undergoes a modified radical mastectomy with axillary lymph node dissection. The resected lymph nodes are carefully examined for evidence of malignant disease (shown in the image). For the surgical specimen described, identify the structure indicated by the asterisk. (A) Afferent lymphatic vessel (B) Cortical sinus (C) Efferent lymphatic vessel (D) Precapillary arteriole (E) Precapillary venule

*The answer is E.* Lymph nodes are characterized by the presence of subcapsular, trabecular, and medullary sinuses that provide channels for the circulation of lymph. The arrows identify a trabecular sinus that appears to be penetrating the cortex of the node (shown in the image). Trabecular sinuses drain to central medullary sinuses. Trabeculae are composed of dense connective tissue. They are continuous with the capsule and provide a framework for lymph node architecture. None of the other regions/structures exhibit histologic features of a trabecular sinus.

A 55-year-old woman with breast cancer undergoes a modified radical mastectomy with axillary lymph node dissection. The resected lymph nodes are carefully examined for evidence of malignant disease (shown in the image). Identify the region of the lymph node indicated by the arrows. (A) Lymphatic vessel (B) Medullary cord (C) Medullary sinus (D) Subcapsular sinus (E) Trabecular sinus

*The answer is C.* The corona of small lymphocytes that surrounds the germinal centers in secondary lymphoid follicles is referred to as the mantle zone. These small lymphocytes include resting T and B cells. Immunohistochemical labeling assays are used to distinguish between these lymphocyte subpopulations. In addition to lymphocytes, nodular lymphatic tissue is characterized by the presence of follicular dendritic cells that trap antigenic debris for uptake by antigen-presenting cells. None of the other histologic features exhibit the morphology of the mantle zone in a secondary lymphoid nodule.

A 59-year-old man with adenocarcinoma of the large intestine undergoes a right hemicolectomy. Microscopic examination of the surgical specimen reveals lymphatic tissue in the lamina propria of the distal ileum (shown in the image). For the surgical specimen described, what is the appropriate name for the corona of lymphocytes that surrounds the germinal centers of these lymphoid follicles? (A) Cortical matrix (B) Lymphoid sheath (C) Mantle zone (D) Primary cortex (E) Secondary center

*The answer is B.* The lymphoid nodules shown in the image exhibit central, pale stained germinal centers that are filled with proliferating B lymphocytes (plasmablasts). These secondary lymphoid follicles (nodules) are similar in morphology to the nodule present in the thyroid gland. The distal ileum is characterized by the presence of multiple lymphatic nodules, referred to as Peyer patches. These aggregates of nodular lymphoid tissue play a crucial role in regulating immune surveillance of the gut flora. Specialized epithelial microfold (M) cells sample antigens present in the lumen of the gut and transport them to the underlying lymphoid tissue to stimulate immune activation or anergy (tolerance). None of the other structures exhibit the morphology of a germinal center in a secondary lymphoid follicle.

A 59-year-old man with adenocarcinoma of the large intestine undergoes a right hemicolectomy. Microscopic examination of the surgical specimen reveals lymphatic tissue in the lamina propria of the distal ileum (shown in the image). Identify the area indicated by the arrows. (A) Diffuse lymphatic tissue (B) Germinal center (C) Medullary sinus (D) Periarteriolar sheath (E) Primary lymphoid follicle

*The answer is B.* The formation of germinal centers for B-cell proliferation in each node's cortex causes swelling.

A 6-year-old boy is brought to the clinic where his mother reports that was bitten by a neighbor's dog two days earlier. The child's right hand is lacerated between the thumb and index finger and this area is inflamed but healing. The doctor's examination reveals small but painless swellings beneath the skin inside the right elbow and arm pit and he explains to the mother that these are active lymph nodes enlarged in response to the infection in the hand. What has produced the swelling? a. Increased flow of lymph through the nodes' afferent lymphatics b. Formation of germinal centers for B-cell proliferation in each node's cortex c. Arrival of antigen-presenting cells in each node's medulla d. Enlargement and increased activity of the nodes' high endothelial venules e. Increased thickness of each node's paracortex

*The answer is B.* The image shows an efferent lymphatic vessel in the medulla near the hilum of a lymph node. Most lymphocytes leave lymph nodes through a common efferent lymphatic channel. Afferent lymphatic vessels (choice A) enter lymph nodes by penetrating the outer capsule. A large afferent lymphatic vessel is visible along the right side of this specimen (shown in the image). Unlike lymphatic channels, a medullary sinus (choice C) would contain medullary cords. Similarly, blood vessels (choices D and E) would contain WBCs and RBCs.

A 69-year-old man with high-grade prostatic adenocarcinoma receives radiation and chemotherapy, but eventually expires. The patient's para-aortic lymph nodes are examined at autopsy for evidence of malignant disease (shown in the image). Identify the channel/space indicated by the arrows. (A) Afferent lymphatic vessel (B) Efferent lymphatic vessel (C) Medullary sinus (D) Precapillary arteriole (E) Precapillary venule

*The answer is B.* The image shows secondary lymphoid follicles near the periphery of a lymph node. The follicles are separated from the capsule by a subcapsular sinus. Germinal centers within secondary lymphoid follicles frequently contain follicular dendritic cells. These large cells have multiple, hair-like processes that intercalate B lymphocytes to support their maturation. Follicular dendritic cells express cell surface Fc receptors that bind antigen-antibody (immune) complexes and store them for weeks (and even years). Follicular dendritic cells do not qualify as antigen-presenting cells (APCs), because the antigens they trap are not internalized and processed for display by MHC molecules; rather, the antigens are merely retained at the cell surface for "inspection" by passing lymphocytes. Dendritic cells (choice A) are typically located in T-cell-rich areas of the deep cortex. None of the other cells display histologic features of follicular dendritic cells.

A mediastinal lymph node is collected at autopsy and examined in the pathology department (shown in the image). The germinal centers of these secondary lymphoid follicles contain nonimmune cells with thin, hairlike processes that intercalate maturing B lymphocytes. Name these nonimmune cells of the reticular meshwork. (A) Dendritic cells (B) Follicular dendritic cells (C) Langerhans cells (D) Macrophages (E) Reticular cells

*The answer is E.* Most lymphocytes in the periarteriolar lymphoid sheath (PALS) are T cells. Thus, PALS are similar in function to the deep cortical region in lymph nodes; both are said to be thymus-dependent lymphoid zones. The mechanisms whereby T lymphocytes exit the blood and congregate around the central artery and its branches are poorly understood. Although the other cells listed are found in diffuse and nodular lymphatic tissue, they are not the principal component of PALS in the spleen.

A microscopic field of the specimen reveals a diffuse halo of cells surrounding a central arteriole (shown in the image). Identify the cells that constitute this periarteriolar lymphoid sheath. (A) B lymphocytes (B) Macrophages (C) Memory B lymphocytes (D) Plasma B cells (E) T lymphocytes

*The answer is A.* The histologic feature identified in the image represents a remnant of epithelial tissue derived from third and fourth pharyngeal pouches during embryonic development. These structures are referred to as Hassall corpuscles. They are a distinguishing feature of the medulla of the thymus. Hassall corpuscles are composed of concentric whorls of type VI epithelioreticular cells. Six functionally distinct populations of epithelioreticular cells have been described. These cells provide a framework for thymocytes and regulate crucial aspects of T-cell education. Herring bodies (choice B) are dilated terminal axons of neurons in the posterior pituitary. Mallory bodies (choice C) represent precipitated intermediate filament protein in the hepatocytes of chronic alcoholics. Meissner and Pacinian corpuscles (choices D and E) are tactile receptors in the dermis of the skin.

A neonate with TORCH syndrome develops respiratory insufficiency and expires. A lobule of the thymus is examined at autopsy (shown in the image). The structure indicated by the arrow shows concentric layers of epithelial cells derived from pharyngeal pouches during embryogenesis. Name this distinctive histologic feature of the medulla of the thymus. (A) Hassall corpuscle (B) Herring body (C) Mallory body (D) Meissner corpuscle (E) Pacinian corpuscle

*The answer is A.* T lymphocytes are preferentially located in the paracortex of lymph nodes, whereas B lymphocytes are found in lymphoid nodules located in lymph nodes, tonsils, and the spleen.

After their maturation in the thymus and release into the circulation, T lymphocytes migrate preferentially to which of the following sites? (A) Paracortex of lymph nodes (B) Cortical lymphoid nodules of lymph nodes (C) Hilus of lymph nodes (D) Lymphoid nodules of the tonsils (E) Lymphoid nodules of the spleen

*The answer is B.* The image shows a channel embedded in connective tissue between thymic lobules. The channel is filled with a monomorphic population of small lymphocytes (presumably thymocytes). The absence of red blood cells within the vessel lumen (see image of Question 9 for comparison) suggests that it is a lymphatic channel. Because the thymus lacks afferent lymphatic channels, this channel most likely represents an efferent channel. Efferent lymphatic vessels accompany blood vessels and nerves through the subcapsular and trabecular connective tissue. None of the other channels describe the morphology of lymphatic vessels in the thymus.

Cortical thymocytes are examined at high magnification in the histology laboratory. Further examination of the specimen reveals numerous thymocytes clustered within a channel that courses through connective tissue between adjacent lobules (shown in the image). What is the appropriate name for this channel? (A) Afferent lymphatic vessel (B) Efferent lymphatic vessel (C) Medullary sinus (D) Postcapillary venule (E) Precapillary arteriole

*The answer is D.* The spleen filters the blood. It removes pathogens and initiates immune response. The spleen also removes senescent and defective RBCs and retrieves iron from hemoglobin. The average life span of circulating RBCs is 120 days. With each pass through the red pulp of the spleen, RBCs must deform so as to squeeze through parallel stacks of long endothelial cells (so-called stave cells) that line the venous sinuses. This open circulation (from sheathed capillaries, to splenic cords, to venous sinuses) provides an opportunity for macrophages to remove RBCs that may be fragile or stiff. Macrophages also have receptors for phosphatidylserine molecules that appear on the outer leaflet of the RBC lipid bilayer following membrane damage. Kupffer cells (choice C) are resident macrophages in the liver. None of the other cells remove defective RBCs from the circulation in the spleen.

During a hematopathology conference you are asked to list and discuss functions of the spleen. Which of the following cells removes senescent and defective RBCs from the circulation in the spleen? (A) Dendritic cells (B) Endothelial cells (C) Kupffer cells (D) Macrophages (E) Reticular cells

*The answer is B.* As mentioned above, negative selection of immature T lymphocytes takes place in the medulla of the thymus during infancy and childhood. In this protected environment, MHC-restricted thymocytes encounter a variety of self-antigens that are displayed on the surface membranes of epithelioreticular cells. Up-regulation of self-antigens (e.g., insulin) on the surface of thymic reticuloepithelial cells is controlled by the autoimmune regulator (AIRE) gene product—a transcription factor. Thymocytes that are self-reactive undergo programmed cell death (negative selection). Macrophages (choice D) remove the residual apoptotic bodies of these self-reactive thymocytes. None of the other cells regulate T-cell education in the thymus.

During a hematopathology conference, you are asked to discuss mechanisms of T-cell "education" in the prepubertal thymus. Which of the following cells regulates negative selection of self-reactive thymocytes in the medulla of the thymus by expressing a wide variety of tissue-specific genes? (A) Dendritic cells (B) Epithelioreticular cells (C) Langerhans cells (D) Macrophages (E) Reticular cells

*The answer is C.* The thymus normally develop less functionality and increasing amounts of adipose tissue with age.

Many immune-related cellular activities are often impaired in aged patients. Which lymphoid organ(s) normally develop less functionality and increasing amounts of adipose tissue with age? a. Axillary lymph nodes b. Lingual tonsils c. Thymus d. Splenic white pulp e. Splenic red pulp

*The answer is C.* The photomicrograph provides a low magnification view of a lymph node. This secondary lymphoid organ is composed of a peripheral cortex and a pale stained, central medulla. Numerous lymphatic nodules are present in the cortex. The hilum, seen on the lower right side of the image, provides a region for blood vessels and an efferent lymphatic channel to enter and/or exit the lymph node. Lymph nodes filter the lymph, removing macromolecular antigens, and they provide a microenvironment for antigen-driven activation of B and T lymphocytes. None of the other lymphoid organs exhibit the distinctive morphology of a lymph node.

Primary and secondary lymphoid organs are examined in the histology laboratory. Identify the organ shown in the image (low magnification). (A) Bone marrow (B) Lingual tonsil (C) Lymph node (D) Spleen (E) Thymus

*The answer is E.* Primary lymphoid organs generate immature B and T lymphocytes; these organs include the bone marrow and thymus. Secondary lymphoid organs provide an environment for antigen stimulation and clonal selection; these organs include (1) diffuse and nodular lymphoid tissue; (2) lymph nodes, and (3) spleen. The image shows the distinctive lobular architecture of the thymus. The lobules are separated by connective tissue trabeculae that originate from a thin capsule. Each lobule is composed of a dark-stained cortex (cortical cap) and a light-stained medulla. The medullary regions are continuous. The cortex and medulla are populated by T lymphocytes (thymocytes) at various stages of differentiation. Reticuloepithelial cells form an extensive meshwork that organizes thymocytes and regulates their growth and development. At low magnification, thymic lobules look like secondary lymphoid follicles with germinal centers (choices B and C); however, lymphoid follicles in mucosa-associated lymphoid tissue are not separated by trabeculae, and lymph nodes have subcapsular, trabecular, and medullary sinuses. The thymus undergoes atrophy after puberty and is replaced by adipose tissue (thymic involution). None of the other lymphoid tissues/organs exhibit the distinctive lobular morphology of the prepubertal thymus.

Primary and secondary lymphoid organs are examined in the histology laboratory. Identify the organ shown in the image (low magnification). (A) Bone marrow (B) Lingual tonsil (C) Lymph node (D) Spleen (E) Thymus

*The answer is D.* The image shows a low magnification section through the spleen. Examination of the specimen reveals scattered splenic lymphoid nodules (white pulp) surrounded by small venous sinuses (red pulp). A dense connective tissue capsule encloses the spleen from which numerous trabeculae penetrate the parenchymal tissue. The spleen filters the blood, removing aged and defective RBCs. The spleen also provides a microenvironment for generating immune responses to blood-borne antigens. None of the other lymphoid organs display red and white pulp.

Primary and secondary lymphoid organs are examined in the histology laboratory. Identify the organ shown in the image (low magnification). (A) Bone marrow (B) Lymph node (C) Peyer patch (D) Spleen (E) Thymus

*The answer is D.* The major complex containing iron, occurs most actively in the spleen.

Recycling of iron and heme, the major complex containing iron, occurs most actively in which lymphoid organ(s)/tissue(s)? a. Lymph nodes b. Peyer's patches c. Tonsils d. Spleen e. Lymphatic vessels

*The answer is D.* The arrow identifies dense connective tissue in the capsule of the spleen. The capsule and associated trabeculae of the spleen are populated by myofibroblasts. These contractile cells are believed to provide tension on the red pulp to accommodate changes in blood flow and discharge reserves of RBCs as needed. Myofibroblasts also synthesize a variety of extracellular matrix molecules. None of the other cells have been identified in the capsule of the spleen.

The capsule of the spleen is known to contain which of the following connective tissue cells? (A) Dendritic cells (B) Epithelioreticular cells (C) Follicular dendritic cells (D) Myofibroblasts (E) Reticular cells

*The answer is D.* Plasma cells are antigen-presenting cells that secrete immunoglobulins.

The plasma cell A. differentiates from T-lymphocytes following antigenic stimulation B. destroys foreign cells by inserting perforins in their membranes C. contains abundant smooth endoplasmic reticulum D. secretes immunoglobulins

*The answer B.* The spleen plays a major in in the destruction of abnormal red blood cells.

The spleen: A. contains numerous germinal centers in the red pulp B. plays a major role in the destruction of abnormal red blood cells C. is the primary erythropoietic organ of the fetus during the last third of pregnancy D. is essential to life E. has sinusoids lined by phagocytic cells

*The answer is A.* B cells give rise to both memory and effector cells and is primarily associated with humoral immunity.

Which cell type gives rise to both memory and effector cells and is primarily associated with humoral immunity? a. B lymphocyte b. NK cell c. Macrophage d. T lymphocyte e. Reticular cell

*The answer is E.* All secondary (peripheral) lymphoid organs contain lymphoid nodules.

Which description is true of all secondary (peripheral) lymphoid organs? a. Capable of antigen-independent lymphopoiesis b. Contain crypts c. Contain epithelial-reticular cells d. Lack connective tissue capsules e. Contain lymphoid nodules

*The answer is A.* All lymphoid tissues and organs produce lymphocytes.

Which function is carried out by all lymphoid tissues and organs? a. Filtration of lymph b. Filtration of blood c. Extramedullary hemopoiesis d. Production of lymphocytes e. Destruction of old erythrocytes

*The answer is D.* Hassall corpuscles are located in the thymic medulla.

Which of the following statements concerning Hassall corpuscles is true? A. They are located in the thymic cortex of young individuals B. They are located in the thymic cortex of older individuals C. They are derived from mesoderm D. They are located in the thymic medulla E. They are derived from T memory cells

*The answer is B.* Epithelial reticular cells of the medulla congregate to form Hassall (thymic) corpuscles.

Which of the following statements concerning the thymus is true? (A) Lymphoid nodules form much of the thymic cortex. (B) Epithelial reticular cells form Hassall corpuscles. (C) T cells migrate into the medulla, where they become immunologically competent. (D) Most T cells that enter the thymus are killed in the medulla. (E) Macrophages are essential components of the blood-thymus barrier.

*The answer is C.* The palatine tonsil is partly encapsulated and covered by nonkeratinized stratified squamous epithelium.

Which structure is partly encapsulated and covered by nonkeratinized stratified squamous epithelium? a. Appendix b. Lymph node c. Palatine tonsil d. Peyer's patch e. Thymic (Hassal's) corpuscle

*The answer is B.* T-lymphocyte precursors arise in the bone marrow, enter the circulatory system, and populate the thymus during fetal development. These multipotential lymphoid stem cells migrate to the cortical region of the thymic lobules. Here, they undergo T-cell receptor gene segment recombination and mutation to generate a heterogeneous population of thymocytes—each bearing a unique cell surface antigen receptor. Unlike surface immunoglobulins on B lymphocytes, T-cell receptors bind antigens that are presented by proteins encoded by the major histocompatibility complex (MHC). None of the other lymphoid organs provide a microenvironment (niche) for T-cell receptor gene assembly.

You are invited to give a research seminar on current topics in immunology. During your presentation, you are asked to explain key steps in lymphocyte differentiation. T-cell receptor gene rearrangement takes place in which of the following anatomic locations? (A) Bone marrow (B) Cortex of the thymus (C) Fetal liver (D) Mantle zone of secondary lymphoid follicles (E) Medulla of the thymus


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