Lymphoid Tissue, ANA LEC - LE 2 PDF

ANATOMY-LEC: LE 2 | TRANS 6 Lymphoid Tissue MARIA LOURDES D. STA ANA, MD, FPDS | Lecture Date (09/30/2024) OUTLINE A. TYPES OF IMMUNE RESPONSE I. Immune...

ANATOMY-LEC: LE 2 | TRANS 6 Lymphoid Tissue MARIA LOURDES D. STA ANA, MD, FPDS | Lecture Date (09/30/2024) OUTLINE A. TYPES OF IMMUNE RESPONSE I. Immune System B. Secondary INNATE IMMUNE RESPONSE A. Types of immune Lymphoid Organs response a. Lymph Nodes Characteristics: Immediate, non-specific, , magnitude of a. Innate Immune b. Spleen c. Mucosa-Associ 📖 the response is the same every time Physical barriers like the skin and mucous membranes of the gastrointestinal, respiratory, and Response ated Lymphoid b. Adaptive Tissue urogenital tracts prevent pathogen entry. Immune d. Bronchus First responders vs pathogens and other foreign Response Associated materials c. Immune Lymphoid Mediated by granulocytes: response Tissue → Ex. activation e. Tonsils ▪ Leukocytes B. Cells of the III. Summary of Key Points ▪ Tissue resident cells Adaptive Immune IV. Review Questions ▪ NK cells response V. References a. Antigen VI. Appendix ADAPTIVE IMMUNE RESPONSE Presenting Response is specific to a pathogen/invader Cells Slow to act at first, but becomes faster with subsequent b. Lymphocytes exposure to the same pathogen due to memory cells II. Lymphoid Organs Mediated by B and T lymphocytes and APCs. A. Primary Lymphoid ➔ There are two types of Adaptive Immune Response: Organs a. Bone Marrow b. Thymus Humoral ○ 📣 Mediated by B lymphocytes which eventually differentiate into plasma cells that would secrete the antibodies SUMMARY OF ABBREVIATIONS ○ Antibodies are produced by plasma cells MALT Mucosa-Associated Lymphoid Tissue (IgA, IgE, IgM, IgG, IgD) PALT Periarteriolar lymphatic sheath Cell-Mediated NK Natural Killer ○ T lymphocytes, with the help of Major RBC Red Blood Cell Histocompatibility Complex, eliminate the 📣 TEC Thymic Epithelial Cells antigen. APC Antigen Presenting Cells ○ Said to be MHC restricted because the MHC Major Histocompability Complex antigen needs to be presented together GALT Gut Associated Lymphoid Tissue with a MHC before a T lymphocyte will be LV Lymphatic Vessels able to recognize it to present it to a B HEV High endothelial venules lymphocyte for destruction CT Connective Tissue IMMUNE RESPONSE ACTIVATION ❗️ 📣 📖 📋 Must know Lecturer Book Previous Trans 1. Macrophages ingest and process a pathogen to display its antigen on its cell surface. a. These macrophages are then referred to as APCs LEARNING OBJECTIVES 2. APCs bind with T helper cells that are capable of Describe the 2 types of Immune Response recognizing the same antigen before releasing IL-1 to ✔ Classify the 2 types of lymphoid organs signal the T helper cell to release IL-2. ✔ Describe the origin, cytology and function of the cells 3. IL-2 is responsible for signaling the proliferation of B cells of the immune system and cytotoxic T cells ✔ Describe each lymphoid organ as to its: a. Response of Cytotoxic T cells o Anatomical structure i. Aside from macrophages, normal cells infected o Distinguishing histological features and with pathogens can also present antigens on function their cell surfaces. Cytotoxic T cells bind to these antigens and facilitate cell death in order I. IMMUNE SYSTEM to destroy the pathogen. b. Response of B Cells A network of immune cells found within lymphoid organs i. Activated B Cells can differentiate into plasma and other tissues, blood, and lymph cells which release antibodies into the Linked together by blood and lymphatic circulation bloodstream. Immune cells protect the body from diseases and ii. These antibodies bind to the antigen infections through an immune response responsible for the infection to mark them for macrophage absorption. LE 2 TRANS 6 TG-C17: Tanael, Tesorio, Timbang, Tindan, Tirado, Titong, Tiu, TE: Tia AVPAA: S. Y. Tan Page 1 of 14 H.  iii. They can also become memory B cells which ➔ Small spherical nucleus provides immunity during subsequent ➔ Coarse chromatin appearing as clumps infections ➔ Mature and become functional in primary lymphoid 📣 REMEMBER organs NK cells, and T and B-lymphocytes can only be Humoral immune response: the B lymphocytes are distinguished through surface proteins in B-lymphocytes involved, and if B lymphocytes are involved there and cd markers in T-lymphocytes using would be production of plasma cells, and these immunohistochemical methods. plasma cells would then produce the immunoglobulins, the antibodies IgA, IgG, IgE, IgM, II. LYMPHOID ORGANS IgD. The Lymphatic System is composed of lymphatic Cell mediated immune response: T lymphocytes vessels that transport interstitial fluid back to the that are involved in elimination of antigen, the blood circulation and the lymphoid organs that house requirement is the foreign body must be attached to a MHC 📣 lymphocytes and other immune cells of the body like the leukocytes, macrophages, and dendritic cells. Lymphoid Organs: ➔ Primary Lymphoid Organs ( lymphocytes) 📣 gives rise to B. CELLS OF THE ADAPTIVE IMMUNE SYSTEM Bone marrow Thymus ➔ Secondary Lymphoid Organs ( activation and proliferation) 📣 site of lymphocyte Lymph node Spleen MALT ➔ Motile Cells in Lymphoid Organs Leukocytes Lymphocytes Macrophages/Dendritic cells Table 1: Classification of Lymphoid Organs Secondary Lymphoid Primary Lymphoid Organs Organs Bone marrow: Lymph nodes Precursor of Spleen T-lymphoblast; Mucosa-associated Maturation of Lymphoid B-lymphocytes and NK Tissues/MALT: cells occur here Comprises of tonsils Thymus: Where and appendix) T-Lymphoblasts pass through to undergo differentiation and maturation to become T-Lymphocytes Give rise to lymphocytes or Site of lymphocyte Figure 1. Lymphocyte Differentiation.[Lecturer’s PPT] immune cells proliferation and activation ANTIGEN PRESENTING CELLS No immune response With immune response Process and Present antigens to lymphocytes (means that there is an ➔ Include: antigen B-Lymphocytes recognised which Macrophages in CT stimulates both Dendritic cells in lymphoid organs the proliferation and Epithelial reticular cells in the thymus activation of ➔ Their function is to activate lymphocytes in the the cells) lymphoid organs via processing and presenting antigens LYMPHOCYTES ❗ All secondary lymphoid organs always have Most numerous in the adaptive immune system lymphoid Regulate and carry out adaptive immunity in secondary lymphoid organs ❗ nodules Do not give rise to precursor Originates in the bone marrow Can mature and become functional in either the bone lymphoblasts marrow or thymus Morphological appearance: ANATOMY Lymphoid Tissue Page 2 of 14  A. PRIMARY LYMPHOID ORGANS Dual embryonic origin ➔ Thymic epithelium originates from the endoderm of BONE MARROW the embryos third pharyngeal pouch with precursor Site of origin for precursor lymphoblasts lymphoblast coming from the bone marrow Gives rise to hematopoietic stem cells (mesodermal origin), invading and differentiating in ➔ myeloid and lymphoid stem cells the thymic epithelium during development. Considered as a lymphoid organ and thus part of the Structural organization lymphoid system because it produces lymphocytes ➔ Encapsulated with trabecula (also called septa) that THYMUS extends into the parenchyma. These trabeculae divide the organ into incompletely separated lobules, 📣 Where T-cells mature and differentiate No immune response occurs here (or in any primary lymphoid organ) each with two distinct regions. Cortex General Characteristics: ○ Outer region ➔ Bilobed ○ Dark stain ➔ Location: anterior mediastinum Medulla ➔ Fully formed and functional at birth, and is most ○ Inner region active in childhood → Undergoes involution at ○ Light stain puberty → the thymus is mostly replaced with fat cells with few remaining lymphoid tissue as we reach adulthood ◆ 📣 This is why it is said that our immune system decreases as we age Primary Function ➔ Development of immunocompetent T-lymphocytes ➔ Induction of central tolerance Figure 3. Thymus: Cortex (Cx) and Medulla (M).[Lecturer’s PPT] Enclosed by a capsule (C) that extends into the parenchyma called trabecula or septa (S), dividing the thymus into incompletely separated lobules: → Each lobule has two distinct regions: ▪ Cortex - outer, deeply staining (occupied by lymphoblasts) Figure 2. Thymus in Children vs in Adults.[Lecturer’s PPT] ▪ Medulla - lightly staining → The difference in the staining of the two regions is Thymus. C - capsule, Co - outer cortex, S - septa, M - due to the greater density of lymphoblasts and small Medulla, A - adipose tissue lymphocytes in the cortex than the medulla 📖Medical Image (b) → The thymus of a child with densely packed, darkly Application staining T lymphoblasts that do not form lymphoid DiGeorge syndrome: Caused by the failure of 💬 nodules Many T lymphoblast cells in the cortex and mature, they enter the medulla after maturation the third and fourth pharyngeal pouches to develop, leading to thymic hypoplasia or aplasia. 💬 Image (c) The thymus in adulthood wherein it decreases in lymphoid tissue mass and cellularity, accompanied by Have severely impaired cell-mediated immunity due to defective T lymphocyte production. reduced T cell output 2 REGIONS OF THE THYMUS 💬 → Tissue is replaced mostly by fat cells Islands of cortex and medulla of the thymus is 1. Cortex Densely populated by T lymphoblasts/lymphocytes, 💬 surrounded by fat cells in adults What the thymus looks like during involution at puberty hence the dark stain → Cortical epithelial cells of the thymus provide a mechanical supporting framework for the developing ANATOMY Lymphoid Tissue Page 3 of 14  T lymphoblasts, and promotes T cell differentiation 2. Negative Selection (2nd stage) and proliferation within the thymus Occurs in the thymic medulla (+) Blood-Thymus barrier Survival depends on not recognizing self-antigen → Epithelium forms sheaths around the blood vessels (antigens in the body of an individual that is not Consists of sets of ○ Epithelial reticular cells and their basal lamina 📖 recognized and acted upon by immune cells) Aire gene (autoimmune regulator) expressed by medullary TECs promotes presentation of ○ Endothelial cells joined by tight junctions → Keeps the antigen in the blood vessels from entering 📖 tissue-specific antigens. Dendritic cells present these antigens to developing T cells. the thymic cortex → Recognize self-antigen? Prevents unregulated exposure of developing T “YES” → Apoptosis 📣 lymphoblasts from antigens in the blood “NO” → Survive and complete maturation → ○ If exposed they might develop an CD4 (T helper cell) / CD8 (T cytotoxic cell) autoimmune response Figure 4. Blood-Thymus Barrier.[Lecturer’s PPT] 2. Medulla 📣 Light staining with T lymphocytes → Contains fewer lymphocytes than the cortex, hence the light stain Hassall Corpuscles → Made of large concentric aggregates of thymic epithelial cells (TEC) that is variable in size → Can be used as a landmark during the lab exam (this → → 📣 would indicate that this is the Thymus) 📣 Most characteristic feature of the medulla Secrete cytokines Regulate dendritic cell activity in the thymus Promote development of regulatory T cells for peripheral tolerance Figure 5. Thymus. H - Hassall Corpuscles.[Lecturer’s PPT] Figure 6. Thymic selection of functional but not self-reactive T cells.[Junqueira’s, 2018] T CELL SELECTION IN THE THYMUS 1. Positive Selection (1st stage) First stage: Positive selection process that occurs in Occurs in the thymic cortex the cortex Survival depends on ability to bind to MHC molecules → The survival of the T lymphoblasts depends on its → Binds to MHC molecule? ability to recognize and bind to an MHC molecule: “YES” → Survive and advance to medulla ▪ If it CANNOT bind, it will undergo apoptosis “NO” → Apoptosis ANATOMY Lymphoid Tissue Page 4 of 14  ▪ If it CAN bind, it will survive and advance to the medulla Second stage: Negative selection process that occurs in the medulla → The survival depends on the inability of T lymphoblast to recognize self-antigens ▪ Self-antigens: antigens present in the body of an individual that is not recognized and acted upon by the immune cell → If it RECOGNIZE a self-antigen, it will undergo apoptosis → If it DOES NOT RECOGNIZE self-antigens, it will survive and complete its maturation and will differentiate into either: Figure 7. Secondary Lymphoid Nodule. GC - Germinal ▪ CD4 or T4/T-helper cell center.[Lecturer’s PPT] ▪ CD8 or T8/T-Cytotoxic cell LYMPHATIC CIRCULATION 📣 B. SECONDARY LYMPHOID ORGANS Lymph nodes and lymphatic vessels filter lymph Organs that provide the environment for the throughout the body proliferation and maturation of cells in adaptive immune Lymphatic vessels are blind-ended vessels lined by 📣 response endothelial cells with valves to ensure a unidirectional flow Also where antigens are presented for processing of lymph which will eventually join the blood circulation Connective tissue supported by reticular cells and fibers Afferent lymphatic vessels bring lymph towards the lymph → Dense lymphoid tissue (encapsulated) nodes for filtering by penetrating the convex side of the → Diffuse lymphoid tissue (unencapsulated or with a hemi lymph node capsule) Lymph is then drained into the subcapsular sinus towards Predominance of lymphocytes the trabecular sinus, the medullary sinuses, and finally Formation of lymphoid nodules (made of B lymphocytes exiting to the efferent lymphatic vessels and may or may not have the presence of a Germinal Lymphatic vessels coming from the right upper side of the Center) body will drain into the right lymphatic duct, returning lymph to the bloodstream by the subclavian vein Lymphatic vessels from the rest of the body: the lower 📣 LYMPHOID/LYMPHATIC NODULES extremities, the left side of the trunk, the arms, and the Spherical clusters of B lymphocytes face will drain lymph into the thoracic duct and it will Characteristic of all secondary lymphoid organs join the left subclavian vein to bring lymph back to the 📣 Composed of large aggregates of B cells May appear differently depending on the activity of immune cells within the organ circulation 1. Primary lymphoid nodule 📣 Represented as aggregates of smaller B cells with SUMMARY OF LYMPHATIC CIRCULATION AND DRAINAGE Circulation uniform cell density and staining (said to be Naive B Afferent lymphatic vessels → Convex side of lymph lymphocytes) nodes → Subcapsular sinuses → Trabecular sinus → Germinal center is absent Medullary sinus → Efferent lymphatic vessels Said to be in a resting state (has not been exposed to Drainage an antigen they recognize) Right upper side of the body → Right lymphatic duct → 2. Secondary lymphoid nodule 📣 More frequently seen than primary lymphoid nodule Right subclavian vein → blood stream Left upper side of the body → Thoracic duct → join with left subclavian vein → brings lymph back to circulation Show aggregates of larger B lymphocytes with more euchromatic cells seen as the lighter germinal center that represent the active site of lymphocyte proliferation → If you see the GC that would mean the B Lymphocytes have recognized the antigen presented to them leading to proliferation The rapid proliferation of activated B lymphocytes causes the small lymphocytes to be pushed aside, forming an outer ring surrounding the germinal center called the “marginal zone” → 📣 In newer references the Marginal zone is also called the “Mantle” (these are the same) Figure 8. Lymphatic Circulation.[Lecturer’s PPT] ANATOMY Lymphoid Tissue Page 5 of 14  LYMPH NODES 📣 Bean-shaped, encapsulated 📣 Measure around 10mm to 2cm in size Distributed throughout the body along the lymphatic vessels 📣 (+) afferent/efferent LV → Has a convex surface where afferent lymphatic vessels enter and a concave hilum where efferent lymphatic vessels leave → 📣 This is the only lymphoid organ that has both 📣 afferent and efferent Blood vessels and nerve penetrate the lymph node Primary function: filter lymph → Defend against the spread of antigens and tumor cells that have invaded the different organ tissues → It is in the lymph nodes where antigen is presented to Figure 10. Structure of the lymph node. C - capsule, immune cells that trigger the development of plasma S - subcapsular sinus, TS - trabecular sinus, T - trabecula, cells into antibodies CS - cortical sinus, MS - medullary sinus.[Young] REGIONS OF A LYMPH NODE 1. Cortex Figure 9. Lymph Node.[Junqueira’s, 2018] STRUCTURAL ORGANIZATION Encapsulated by dense connective tissue → Extends as trabeculae within the lymph node parenchyma Figure 11. Regions of a lymph node. C - cortex, P - Lymph drainage thru sinuses: paracortex, M - medulla, CT - connective tissue of → Subcapsular sinus → trabecular or cortical sinus → capsule, T - trabeculae, LN - lymph nodules, MS - medullary sinus medullary sinuses, MC - medullary cords. [Junqueira’s, 2018] ▪ Subcapsular sinus receives lymph from the afferent lymphatic vessels ▪ Exit via efferent lymphatic vessels (+) lymphoid nodules with or without germinal center Reticular connective tissue provides the main Consists of structural support for the lymph node → B lymphocytes → Also forms the core of lymphatic nodules in the cortex and the medullary cords and sinuses in the medulla 📣 → Macrophages/APCs Separated from the connective tissue capsule by the subcapsular sinus which branches out into cortical and trabecular sinuses 2. Paracortex Region between the cortex and the medulla without lymphoid nodules Contains mostly T-lymphocytes Unique feature: (+) high endothelial venules (HEV) → Specialized post-capillary venules that represent an important entryway for most circulating lymphocytes to the lymph nodes ANATOMY Lymphoid Tissue Page 6 of 14  → Lined by cuboidal cells with apical surface glycoproteins and integrins that allow rapid SPLEEN translocation of lymphocytes → Lymphocytes are intrinsically mobile so they can leave the bloodstream by preferential migration 📖 Intra-abdominal organ Filled with reticular tissue containing reticular cells and fibers, many lymphocytes and other blood cells, across walls of HEVs to the paracortex by selective diapedesis → Also found in the mucosa-associated lymphoid tissue 📣 macrophages, and APCs Located in the left upper quadrant of the abdomen although not as prominent as that found in the lymph node 📣 behind the stomach Typically measures around 12 by 3 by 7 centimeters in size → Tends to decrease slowly in size after puberty Largest organ of the immune system Functions: → Filtration of blood ▪ The only lymphoid organ involved in the filtration of blood ▪ Important in the defense against blood-borne 📖 📖 antigens → Main site of old erythrocyte destruction → Volume varies with its content of blood and tend to decreased very slowly after puberty Encapsulated by a dense connective tissue capsule that extend inward forming the trabeculae through which blood vessels enter the pulp → 📣The trabeculae is where the blood vessels enter the pulp or the splenic pulp Figure 12. High endothelial venules. [Junqueira’s, 2018] → 📣There are also specific identifiable regions in the splenic parenchyma (white pulp and red pulp) 3. Medulla Distinguishing features: → Medullary cords ▪ Branched cord-like masses of lymphoid tissue with T and B lymphocytes and plasma cells → Medullary sinuses ▪ Dilated spaces separating the medullary cords that discontinues with the cortical sinuses ▪ Converge at the hilum to form and drain into the efferent LV ▪ Consist of reticular cells and plenty of macrophages Figure 14. Spleen. C - capsule, T - trabeculae, R - red pulp, W - white pulp. [Junqueira’s, 2018] SPLENIC PULP 1. White Pulp Splenic/lymphoid nodule → In fresh specimens, it appears as white surrounded by the red pulp filled with immune cells and RBCs Central arteriole PALS 2. Red Pulp Figure 13. Lymph node medulla. MS - medullary sinuses, Splenic cords MC - medullary cords, Arrows - plasma cells. [Junqueira’s, 2018] Splenic sinusoids (spaces in between) → Stave cells 📖Medical Application: Metastatic cancer cells can spread to lymph 📣 The term white pulp and red pulp comes from the appearance of a freshly cut spleen nodes, especially the sentinel lymph node. Cancer cells in lymph nodes may lead to the formation of secondary tumors. ANATOMY Lymphoid Tissue Page 7 of 14  ▪ Course between the cords ▪ Lined by specialized endothelial cells called Stave Cells Stave Cells → Oriented parallel to the direction of the blood flow → Elongated endothelial cells with large nuclei bulging into the sinusoidal lumen → Highly discontinuous basal lamina that is open to the passage of RBCs Figure 15. White Pulp. W - white pulp, R - red pulp, → Function: Arrowhead - central arteriole. [Junqueira’s, 2018] ▪ Allow lymphocytes, platelets, and younger RBCs 📖 to enter the sinusoids Blood flow through the splenic red pulp can take either closed circulation or open circulation Figure 17. Splenic sinusoid of the spleen lined by Stave Cells [Junqueira’s Basic Histology 16th ed, Chapter 14, page 292] Figure 16. Red Pulp. S - sinusoids, C - splenic cords, Arrows - endothelial cells. [Junqueira’s, 2018] WHITE PULP Composition → Splenic/lymphoid nodule ▪ Made up of cluster of B-lymphocytes with a germinal center → Central arteriole of the trabecular artery ▪ The term “Central Arteriole” is a misnomer because it is not really centrally-located but is found at the periphery of lymphoid nodule o Pushed aside because of the proliferating o 📖 lymphocytes In growing nodules, the arteriole is pushed to eccentric position, send capillaries throughout Figure 18. Blood flow in the Spleen [Junqueira’s Basic Histology 16th ed, the white pulp and to small sinuses in a Chapter 14, page 289] peripheral marginal zone of developing B cells Splenic Circulation o 📖 around each lymphoid nodule Each central arteriole eventually leaves the white pulp and enters the red pulp, losing its → Splenic artery branches to trabecular arteries that give off small branches called central arterioles that become enclosed with PALS within the white pulp, it branches sheath of lymphocytes and branching as into several penicillar arterioles which then lead to several straight penicillar arterioles that capillaries surrounded by macrophages. From the ▪ 📣continue as capillaries This is the distinct characteristic of of a white pulp capillaries, blood flows into either a closed circulation or to an open circulation. Closed Circulation → Periarteriolar lymphatic sheath (PALS) → Capillaries connect directly to the sinusoids ▪ Surrounds the central arteriole and composed of ▪ Blood will go to sinusoid and drains to the veins T lymphocytes → Capillaries branching from the penicillar arterioles join RED PULP directly to the sinusoids so blood is always enclosed by Forms the bulk of the splenic parenchyma and the site the endothelium where swollen RBCs are removed Open Circulation Composition: → Capillaries branching from some penicillar arterioles are → Splenic/Billroth cords open-ended which means that they are not connected ▪ Made up of reticular cells and fibers, containing to sinusoids. From these open-ended capillaries, blood lymphocytes, macrophages, leukocytes, and is released into the stroma of the splenic cords. RBCs → Splenic sinusoid ANATOMY Lymphoid Tissue Page 8 of 14  → Plasma and other formed elements of the blood re-enter the vasculature through the narrow slits of stave cells into the sinusoids. → However, when the swollen RBCs have reached their life span of 120 days are blocked by the stave cells. These RBCs left in the red pulp undergo selective removal by macrophages ▪ The young RBCs are still flexible and able to re-enter via stave cells MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT) Peripheral lymphoid tissue that responds to antigens that enters the body through the mucosa. Structural characteristics → Diffuse populations of lymphocytes, IgA, APCs located in the mucosal connective tissue scattered along mucosal surfaces of gastrointestinal tract, respiratory tract, and genitourinary tract Figure 19. Section of Peyer’s patches showing lymphoid → Unencapsulated or with a hemicapsule (partial capsule) nodules (N), germinal center in the submucosa (arrow), and → Lymphoid nodules (solitary / aggregates) villi (V)[Junqueira’s Basic Histology 16th ed, Chapter 14, page 283] ▪ Seen as aggregates of lymphoid nodules in tonsils and Peyer’s patches in ileum and appendix Protect the mucosa of these organs since their common sites have pathogenic invasion because their lumen opens to the external environment. GUT ASSOCIATED LYMPHOID TISSUE: 1. Solitary Lymphoid Nodules Widely distributed throughout the body that can be transitory structures → 📣 Once a mounted immune response is done, the different immune cells that make up this transitory structure will disperse/recirculate and go back to the different tissues of the body Commonly located in connective tissue underlying mucosal epithelium E.g. found in the Esophagus and in the Colon 2. Aggregated Lymphoid Nodules Best observed in the Peyer’s patches found in the Figure 20. Schematic diagram showing how luminal antigens ileum and also in the appendix are taken up and processed by lymphoid nodules in the Small accumulations of lymphocytes or solitary lymph Peyer’s patches[Junqueira’s Basic Histology 16th ed, Chapter 14, page 283] follicles are found scattered throughout the gastrointestinal tract Antigens in the lumen are bound by M Cells (Microfold The most prominent accumulation of lymphocytes cells) occurs in the ileum called Peyer’s Patches M cells are transported into the intraepithelial pockets → Peyer’s Patches where antigens are taken up by dendritic cells to be ▪ Dome-shaped M cells in the covering of Peyer’s presented to the T helper cells patches capture luminal antigens for B lymphocytes are stimulated by the T Helper cells to 📣presentation to T lymphocytes. differentiate into plasma cells, secreting IgA antibodies o M cells are well developed in the peyer’s IgA antibodies are then transported into the gut lumen patches but they are also present in the tonsils where it binds to antigens, neutralizing potential harmful and the MALTs microorganisms before the intestinal pathogens penetrate ▪ Aggregates of lymphoid nodules in the ileum the mucosa. ▪ Beneath the epithelium lining of the domes, Peyer’s patches have lymphoid nodules with BRONCHUS ASSOCIATED LYMPHOID TISSUE: germinal centers, typically located in the Constitutes mucosal lymphoid tissue adjacent to submucosa. major airways Protects underlying mucosa from airborne antigens ANATOMY Lymphoid Tissue Page 9 of 14  → Partially encapsulated by dense CT (hemicapsule) ▪ Separated tonsils from underlying muscle tissue → Lumen of the crypts may contain desquamated ▪ 📣 epithelial cells, dead lymphocytes, and bacteria During infections, the visible white spots are the tonsillar crypts → Dense infiltrates of lymphocytes and leukocytes ▪ 📣 lining epithelium Such that the lining epithelium of the palatine tonsils would also have leukocytes and lymphocytes Figure 21. Collection of lymphatic tissue seen under bronchiolar epithelium[Lecturer’s PPT] Figure 22. Debris laden macrophages stained dark[Lecturer’s PPT] Figure 24. Palatine tonsil: surface with stratified squamous non-keratinized epithelium (E), tonsilar crypts (C), lymph TONSILS nodules (LN), connective tissue (CT), and germinal centers Large, irregular masses of lymphoid tissue in the mucosa (GC) [Lecturer’s PPT/Junquera’s Basic Histology] of the posterior oral cavity and nasopharynx close to the → ❗️ epithelium Closely associated with the epithelium Where immune cells encounter pathogens entering the mouth and nose Considered organs named according to location Includes the palatine, lingual, and pharyngeal tonsils 📣 Closely associated with the surface epithelium Important in neutralizing or surveillance of pathogens that entered the body Figure 23. Types of tonsils; named based on their location[Lecturer’s PPT] Figure 25. Palatine tonsil. [Netter’s Essential Histology with Correlated Histopathology 3E, Chapter 9] PALATINE TONSIL Located posteriorly on the lateral wall of the pharynx/ oral LINGUAL TONSIL cavity Located along the base of the tongue Luminal surface lined by stratified squamous Covered by stratified squamous non-keratinized non-keratinized epithelium epithelium − 📖 → (+) 10-20 invaginations forming tonsillar crypts Invaginations or tonsillar crypts is densely infiltrated with lymphocytes and other leukocytes → (+) lymphoid nodules → (+) singular crypts ▪ In comparison to Palatine where there are multiple ▪ Increase the surface area for antigen sampling by crypts lymphoid tissue beneath → Lacks distinct capsule → (+) lymphoid nodules distributed along the lengths of the ▪ Lacks hemicapsule compared to palatine tonsil tonsillar crypts (invaginations towards the palatine tonsils) ANATOMY Lymphoid Tissue Page 10 of 14  Tonsillitis: Inflammation of the tonsils, more common in children. Chronic inflammation can lead to tonsillar hyperplasia and the formation of adenoids, potentially obstructing the eustachian tube and causing middle ear infections. III. SUMMARY OF KEY POINTS Immune System and Lymphoid Organs Figure 26. Location of the Lingual and Palatine tonsils (Left). →The immune system consists of immune cells found Lingual tonsil histology showing singular tonsilar crypt (Right). within lymphoid organs and other tissues in the body [Lecturer’s PPT] → Function: immune cells protect the body from diseases and infections through an immune response PHARYNGEAL TONSIL 2 types of immune response: 📣 Located at the posterior wall of the nasopharynx → Innate immune response → respiratory epithelium lining ▪ Mediated by granulocytes, tissue resident cells, NK Lined by pseudostratified columnar ciliated epithelium cells → (+) lymphoid nodules ▪ Immediate, non specific, magnitude of response is the 📣 → (-) crypts same every time ▪ Instead of crypts, it has invaginations or shallow → Adaptive immune response folds ▪ Mediated by lymphocytes and APCs ▪ Immune response against specific pathogens ▪ Slow initially, will produce a faster, stronger response with subsequent exposure ▪ Produces memory cells Cells involved in Adaptive Immunity: → Antigen Presenting Cells (macrophages/dendritic cells/epithelial reticular cells) ▪ Process and present antigens to lymphocytes in lymphoid organs → Lymphocytes ▪ Small cells with a spherical basophilic nucleus ▪ Thin rim of basophilic cytoplasm Figure 27. Pharyngeal tonsil showing infoldings and ▪ Function: regulate and carry out adaptive immunity lymphoid nodules. [Lecturer’s PPT] Lymphoid Organs Classification: → Primary Lymphoid Organs ▪ Gives rise to lymphocytes/immune cells ▪ No immune response → Secondary Lymphoid Organs ▪ Site of lymphocyte activation and proliferation → Motile Cells in Lymphoid Organs ▪ Leukocytes ▪ Lymphocytes ▪ Macrophages/Dendritic Cells Primary Lymphoid Organs → Bone marrow Figure 28. Location of pharyngeal tonsil. [Lecturer’s PPT] ▪ Site of origin for precursor lymphoblasts ▪ Gives rise to hematopoietic stem cells ❗️ → myeloid and lymphoid stem cells → Thymus ▪ Site of T cell maturation and differentiation ▪ Bilobed, found on the anterior mediastinum, involutes in adulthood ▪ Has a cortex and medulla ▪ Presence of Hassal corpuscles and epithelial reticular cells of the blood-thymus barrier Secondary Lymphoid Organs ▪ Predominance of lymphocytes ▪ Presence and formation of lymphoid nodules → Lymph nodes Figure 29. Similarities, differences, and unique features of ▪ Bean-shaped, distributed throughout the body for each lymphoid organ. [Lecturer’s PPT] lymph filtration ▪ Presence of: 📖Medical Application: Tonsillitis → both afferent and efferent lymphatic vessels, → cortex, ANATOMY Lymphoid Tissue Page 11 of 14  → paracortex with high endothelial venules, and → medulla with medullary cords and sinuses → Spleen ▪ Intra-abdominal organ, primarily for blood filtration ▪ Presence of: → white pulp with the lymphoid nodules, the central arteriole, and periarteriolar lymphatic sheath, → red pulp with splenic cords and sinusoids, and stave cells → Mucosa-Associated Lymphoid Tissue (MALT) ▪ Peripheral lymphoid tissue that responds to antigens that enters the body through the mucosa ▪ Presence of M cells and crypts → GALT ▪ Solitary lymphoid nodules in the esophagus and colon ▪ Aggregated lymphoid nodules in Peyer’s patches of the ileum and appendix → BALT a. Lymph Node ▪ Mucosal lymphoid tissue adjacent to major b. Tonsil airways, protecting mucosa from airborne pathogens c. Spleen → Tonsils d. Thymus ▪ Large, irregular masses of lymphoid tissue in the 3. Lymphoid nodules are characteristic features of the mucosa of the posterior oral cavity and nasopharynx, following organs EXCEPT: encountering pathogens at the mouth and nose a. Pharyngeal Tonsil → Palatine Tonsil b. Thymus ▪ Posterior to the lateral wall of the pharynx/ oral c. Spleen cavity d. Lymph Node ▪ Surface lined by stratified squamous 4. Identify the whole organ: non-keratinized epithelium ▪ Presence of multiple tonsillar crypts, lymphoid nodules, hemicapsule → Lingual Tonsil ▪ Along the base of the tongue ▪ Also lined by stratified squamous non-keratinized epithelium ▪ Less tonsillar crypts, presence of lymphoid nodules → Pharyngeal Tonsil ▪ Posterior wall of the nasopharynx ▪ Lined by pseudostratified columnar ciliated epithelium ▪ Has lymphoid nodules, lack of tonsillar crypts would instead have invaginations/shallow folds IV. REVIEW QUESTIONS 1. Which type of immune response is involved in the activation of B lymphocytes? a. Lymph node a. Innate b. Palatine tonsil b. Humoral c. Spleen c. Cell mediated d. Thymus 2. Identify whole structure 5. Which of the following lymphoid organs are high endothelial venules commonly found? a. Spleen b. Thymus c. Lymph Node d. Bone Marrow ANSWER KEY 1. B Innate response utilizes granulocytes, tissue resident cells, and NK cells, Cell-mediated response utilizes T lymphocytes. 2. C Presence of white and red pulp, Not the lymph due to the lack of a cortex and medulla, Not the tonsil due to the lack of a crypt or infolding, Not the thymus due to the lack of incomplete ANATOMY Lymphoid Tissue Page 12 of 14  lobules or Hassal corpuscles or cortex and b. Peyer’s patches medulla. c. Spleen 3. B Thymus, as a primary lymphoid organ, does not d. Liver have lymphoid nodules 4. A Cortex and medulla (the light staining area with ANSWER KEY the cords and sinuses) are present, Not the palatine tonsil due to the lack of tonsillar crypts, 1. B The thymus is a primary lymphoid organ in Not the spleen as the medulla is present in the charge of T cell maturation and differentiation; image (only have lymphoid nodules The other organs are classified as secondary represented by white pulp surrounded by red lymphoid organs in charge of lymphocyte pulp), Not the thymus as it lacks lymphoid proliferation and activation. nodules (as it is a primary lymphoid organ) 2. A Plasma cells are differentiated B lymphocytes 5. C High endothelial venules are found in the that are capable of antibody secretion. paracortex of the lymph node, No high 3. C All secondary lymphoid organs have efferent endothelial venules in the spleen, Other lymphatic vessels, The lymph node and spleen secondary lymphoid organs that MAY have it have connective tissue capsules, Crypts are are your MALTs like Peyer’s patches (few) and usually found in tonsils (MALTs). the tonsils (not as developed as that in lymph 4. D Another similar structure is the lingual tonsil, node), Primary lymphoid organs (bone marrow, Peyer’s patches are found in the appendix and thymus) do not mount an immune response so submucosa of the ileum, Hassal/thymic they don’t have to have secondary lymphoid corpuscles are found in the medulla of the organ features such as high endothelial thymus, Lymph nodes are encapsulated by venules. dense connective tissue. 5. C The spleen is the only lymphoid organ in charge FORMATIVE QUIZ of blood filtration and processes RBCs in open 1. Among the following organs, what is a primary circulation, blocked by stave cells and lymphoid organ? processed by macrophages in red pulp. a. Spleen b. Thymus c. Lymph node V. REFERENCES 2027 Trans d. MALT Lecturer’s PPT 2. Which of the following cells secrete antibodies? Loyola University Chicago (n.d.). Slide #DMS 117. a. Plasma cells https://zoomify.luc.edu/lymphoid/dms117/popup.html b. T lymphocytes Mescher, A. (2009). Junqueira’s Basic Histology: Text and Atlas c. B lymphocytes (12th ed.). McGraw-Hill. d. NK cells Mescher, A. (2013). Junqueira’s Basic Histology: Text and Atlas 3. What is true of all secondary lymphoid organs? (13th ed.). McGraw-Hill. a. Lack efferent lymphatic vessels Mescher, A. (2015). Junqueira’s Basic Histology: Text and Atlas (14th ed.). McGraw-Hill. b. Lack connective tissue capsules Mescher, A. (2021). Junqueira’s Basic Histology: Text and Atlas c. Contain lymphoid nodules (16th ed.). McGraw-Hill. d. Contain crypts Netter, F. (2019). Atlas of Human Anatomy (7th ed.). Elsevier. 4. Which structure is partly encapsulated and covered Ovalle, W. and Nahirney, P. (2021). Netter’s Essential Histology by non-keratinized stratified squamous epithelium? with Correlated Histopathology (3rd ed.). Elsevier. a. Peyer’s patches University of Leeds. (n.d.). Lymphoid tissue: Lymph nodes. b. Thymic corpuscle https://www.histology.leeds.ac.uk/lymphoid/lymphnodes.php c. Lymph node Winslow, T. (2007). Acute Lymphoblastic Leukemia. https://www.physio-pedia.com/Acute_Lymphoblastic_Leukemia d. Palatine tonsil Young, B., Woodford, P., and O’Dowd, G. (2013). Wheater’s 5. Destruction of RBCs and recycling of iron occurs Functional Histology: A Text and Colour Atlas (6th ed.). Churchill mainly in: Livingstone. a. Tonsils ANATOMY Lymphoid Tissue Page 13 of 14  VI. APPENDIX Table 1. Important Histological Comparisons of Major Lymphoid Organs Thymus MALT Lymph Nodes Spleen Cortex/Medulla Present Absent Present Cortex/Medulla Lymphoid Nodules Absent Present Present (cortex only) Present (white pulp) Lymphatic Vessels (-) Afferents (-) Afferents (+) Afferents (-) Afferents Few efferents (+) Efferents (+) Efferents (+) Efferents Unique Features Hassall Corpuscles Crypts paracortex White pulp w/ central artery Reticular cells M cells HEV Medullary cords & Red pulp with sinuses sinusoids ANATOMY Lymphoid Tissue Page 14 of 14