Histology Of The Immune System And Lymphoid Organs PDF

(006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21...

(006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 OUTLINE b. Well-defined anatomic sites and partially encapsulated I. LYMPHATIC SYSTEM i. Red bone marrow A. Lymph ii. Thymus B. Lymphatic Vessels iii. Lymph nodes C. Lymphoid Tissues iv. Tonsils D. Lymphoid Organs v. Spleen II. SMALL LYMPHATIC SYSTEM (CAPILLARIES III. LYMPHATIC TISSUES AND ORGANS A. Tonsils II. SMALL LYMPHATIC SYSTEM (CAPILLARIES) B. Lymph Nodules C. Lymph Nodes Lymphatic capillaries are responsible for initially IV. HIGH ENDOTHELIAL VENULES (HEV) collecting the lymph before it goes to the pre-collecting and V. LYMPHOMAS collecting lymphatic vessels. It is lined by Simple Endothelial A. Hodkin’s Disease Cells with anchoring filaments. They lack basement membrane. VI. RED BONE MARROW VII. THYMUS A. Maturation process B. T-cell maturation – 2 selection process C. DiGeorge syndrome (Thymic Aplasia) VIII. SPLEEN A. Medical applications IX. REFERENCES X. TEST YOURSELF I. LYMPHATIC SYSTEM A. Lymph Recovered fluid Clear, colorless fluid similar to blood plasma but low in Figure 1. Relationship of a venule and arteriole with lymphatic capillaries involved protein B. Lymphatic Vessels Capillaries Collecting vessels Trunks Collecting ducts C. Lymphoid Tissues a. Lymphoid tissue is usually reticular connective tissue filled with large number of lymphocytes. b. Because lymphocytes have prominent basophilic nuclei and very little cytoplasm, lymphoid tissue with such cells usually stains dark blue in hematoxylin and eosin Figure 2. Electron Microscope showing Terminal Capillaries of the (H&E). Lymphatic Vessels c. Lymphocytes regulate and carry out adaptive immunity d. Lymphocytes aggregate in the connective tissue of mucous membranes and organs i. Diffuse lymphatic tissues ii. Lymphatic nodules D. Lymphoid Organs a. In adults, stem cells for all lymphocytes are located in the red bone marrow, but cells of the major lymphoid lineages mature and become functional in two different central or primary lymphoid organs. Figure 3. LM of a small lymphatic vessel in connective tissue and a lymphatic capillary in transverse section Page 1 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 ○ major sites of lymphocyte production and maturation a. Bone marrow: produces B lymphocytes; major maturation and production of Lymphocytes occur b. Thymus: T lymphocytes i. B cells mediate humoral immunity Mature into Plasma cells synthesize antibodies against Ag’s ii. T cells mediate cellular immunity against microorganisms Once they are activated, they will elicit response that occur in the Figure 4. LM of a small lymphatic vessel in connective tissue. Secondary Lymphoid organs (GALT, Spleen, Tonsils, MALT) Arteriole is much thicker than the Venules and it has two layers of Immune responses smooth muscle on the Tunica Media. The Venule has a thinner wall and a larger lumen. The lymphatic channel has a very attenuated ○ occur in secondary lymphoid organs wall lined by Endothelium. The lumen is irregular and almost lymphoid nodes and spleen collapsed. ➔ ALL LYMPHOID TISSUE derived embryonically from mesoderm, except for the thymus, which arises from III. LYMPHATIC TISSUES AND ORGANS the mesoderm and endoderm (Lymphocytes and cells of the mononuclear system) Mucosa Associated Lymphatic Tissue MALT ○ The mucosa of the digestive, respiratory, and genitourinary tracts is a common site of invasion of pathogens. To protect against invaders, mucosal connective tissue of these tracts contains large and diffuse connections of lymphocytes, IgA-secreting plasma cells, APCs, and lymphoid nodules, all of which comprise the MALT. ○ Diffuse lymphoid tissue common in the connective tissue – found in the lamina propria - of these membranes ○ Collectively, MALT is one of the largest lymphoid organs, containing up to 70% of all the body’s immune cells. Most of the lymphocytes here are B cells. Among T cells, CD4 helper T cells predominate. ○ MALT on the basis of location: Gut-associated Lymphoid Tissue (GALT): Tonsils, Peyer's patches, Figure 5. The lymphoid organs appendix Immunocompetency Immunocompetent cells: Bronchus-associated Lymphoid Tissue React and neutralize Ags (BALT), nose-associated Lymphoid Stroma of reticular cells Tissue (NALT), and vulvovaginal- “reticular connective tissue” associated (VALT) lymphoid tissue Ability to recognize and respond to antigens ○ “self” and “nonself” ○ When you attack your own self antigens, it produces Autoimmune Disease like Systemic Lupus o Erythematosus (SLE) and Hashimoto’s Thyroiditis Divided into Primary and Secondary Lymphoid Tissues Primary lymphoid organs (only Thymus and Bone Marrow belong to the Primary Lymphoid organs and the rest are secondary) Page 2 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 Figure 8. Peyer’s patches Figure 6. GALT. There are aggregates of Lymphoid nodules in the Lamina Propria Clinical Point: Infectious diseases Rubella (German measles) Hallmark erythematous maculopapular rash plus fever and swollen lymph node The portal of entry for the virus is the upper respiratory tract (NALT) through lymphoid tissue Rubella occurs mainly in children and young adults; in pregnant women it poses a serious risk to a fetus (can cause congenital malformation of the child) Vaccine Figure 7. BALT and MALT, Most of the Lymphoid nodules are associated at the Lamina Propria of each organ Primary antibody: IgA: secretory Peyer’s patches Aggregations of lymphatic nodules (T and B lymphocytes) Capture and destroy bacteria in intestines (cytotoxic T cells in mucosa) Figure 9. Lymph node M cells (broad with microvilli) – present in the lumen and they present the antigen to the Lymphoid Nodules then the B cells and T cells on the lymphoid nodules will react to the antigen. Page 3 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 The Palatine Tonsils 5th week: endoderm of 2 pharyngeal pouch proliferates and forms epithelium and tonsillar crypts Mesoderm - stroma of the palatine tonsil 20th week: lymphatic nodules are forming Tubal (a pair), pharyngeal, lingual tonsils Pits – openings of Tonsillar crypts Lining is Stratified Squamous Epithelium A. Tonsils Tonsils are large, irregular masses of lymphoid tissue in the mucosa of the posterior oral cavity and nasopharynx where their cells encounter antigens entering the mouth and nose Late puberty a. Progressive atrophy Blood supply: a. Tonsillar branch of the facial artery Venous drainage: a. The paratonsillar vein, descends from the soft palate across the lateral aspects of the tonsillar capsule b. It is nearly always divided in tonsillectomy and may give rise to troublesome hemorrhage Lymphatic drainage a. Tonsillar or jugulodigastric node at the angle of the jaw Form a ring of lymphatic tissue at the entrance of the oropharynx (aggregations of nodules) Waldeyer’s ring Almond-shaped, 1-2.5 cm Partially encapsulated No afferent lymphatic vessel a. Pharyngeal tonsils (adenoids; posterior part of the oropharynx) Figure 10. Tonsils b. Palatine tonsils (tonsillar crypts; oropharynx) c. Lingual tonsils (base of tongue) Each tonsil is covered with epithelium and have deep pits (tonsillar crypts) lined with lymphatic nodules Trap and remove bacteria and other foreign materials Figure 11. Comparison between a healthy and infected tonsil Page 4 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 4. Recirculation of lymphocytes by their selective re-entry from blood to lymph across walls of specialized efferent lymphatics During development, specific regions of each node are seeded with B lymphocytes from the bone marrow and T lymphocytes from the thymus B cells: cortex (contains B-cells and contain primary nodules) Bone marrow 1. Primary nodules a. Packed with B cell; when activated with Ag+, proceeds to the Secondary Nodules 2. Secondary nodules a. Has GC (Germinal Centers) with mantle zone b. site of B cell proliferation T cells: paracortex (contains the T-cells) o Where Antigen-dependent T cell differentiation and proliferation occurs Capsule – outer part of the Lymph node and it has a trabeculae together with the Subcapsular Sinuses. Beneath the Subcapsular Area is the Cortex and deeper within the Corte is the Paracortex. Figure 12. Tonsillectomy is the process of removing tonsils. B. Lymphoid Nodules (or follicles) Dense aggregations of lymphocytes arranged as spherical, unencapsulated clusters Two types: a. Primary nodule: contains small, immature B lymphocytes b. Secondary nodules, which contain pale-stained germinal centers sites of extensive B lymphocyte proliferation and differentiation into plasma cells: antibody production B cells predominate in nodules and T cells are abundant in adjacent areas C. Lymph Nodes Bean or kidney-shaped lymphoid organs, 2-20 mm, distributed throughout the body along the lymphatic vessels. Figure 13. 3D schematic of a lymph node A total of 400-450 lymph nodes are present in the axillae (armpits) and groin, along the major vessels of the neck, and in the thorax and abdomen, especially in the visceral mesenteries. Main functions: 1. Filtration of lymph before its return to the thoracic duct 2. Production of lymphocytes that are added to lymph 3. Synthesis of antibodies (mainly IgG) Page 5 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 Figure 14. Lymph nodes and lymphatic drainage of mouth and pharynx Figure 17. LM of the outer part of a lymph node and higher magnification LM of part of a lymph node cortex IV. HIGH ENDOTHELIAL VENULES (HEV) ⚫ Specialized endothelial cells of post capillary venules ⚫ Represents an important entry point for most (90%) circulating lymphocytes into lymph nodes. ⚫ HEV: Located in the Paracortex of lymph nodes ⚫ Also occur in the large accumulations of MALT but are less well-characterized ⚫ B and T lymphocytes passes across the endothelial venules Figure 15. Lymph node before coming to germinal center ⚫ Lymphocytes move across the high endothelial venules by diapedesis into the lymph node ⚫ Their endothelial cells are unusually shaped but generally cuboidal and facilitate rapid translocation of lymphocytes from blood into the lymphoid tissue ⚫ Integrins promote adhesion between lymphocytes and the endothelial cells, and the lymphocytes cross the vessel wall into the lymph node parenchyma ⚫ Diameter: 7 - 30um ⚫ Site: Secondary lymphoid organs except spleen (have its own HEV) ⚫ Enable lymphocytes to enter lymph node ⚫ Expresses CD34, MAdCAM-1 Figure 16. Microscopic view of a lymph node Figure 18. High Endothelial Venules Page 6 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 Figure 21. Lymphoma VI. RED BONE MARROW Figure 19. Paracortex: selective diapedesis of B/T cells from the ⚫ Soft, loosely organized, highly vascular material separated blood to perivascular tissues from osseous tissue by endosteum of bone *Does eating sweet foods cause tonsillitis? Bacteria causes tonsillitis ⚫ Usually found in the vertebrae, ribs, sternum, cranium, end of humerus/femur ⚫ Bone Marrow: has Red (produced by an abundance of blood V. LYMPHOMAS and hemopoietic cells) and Yellow Bone Marrow (which is filled ⚫ Are localized lymphocyte malignancies that often form solid with adipocytes that exclude most hemopoietic cells) tumors, mainly affecting lymph nodes ⚫ In the newborn all bone marrow is red and active in blood cell ⚫ are a group of disorders involving neoplastic proliferation of production, but as the child grows, most of the marrow lymphocytes or the failure of these cells to undergo apoptosis changes gradually to the yellow variety. Under certain ⚫ all lymphomas are considered malignant because they can conditions, such as severe bleeding or hypoxia, yellow marrow very easily become widely spread throughout the body. reverts to red ⚫ Common clinical presentations include lymphadenopathy, ⚫ It contains a reticular connective tissue stroma, hemopoietic splenomegaly and hepatomegaly, as well as, fever, weight loss cords or islands of cells, and sinusoidal capillaries and malaise. ⚫ It is also a site where older, defective erythrocytes undergo ⚫ May be generally classified as high and low grade, but there phagocytosis by macrophages, which then reprocess heme- are no truly benign tumors of lymphoid tissues bound iron for delivery to the differentiating erythrocytes. ⚫ As blood cells mature, they push their way through the reticular and endothelial cells to enter the sinusoids and flow away in A. HODGKIN DISEASE (HD) the blood stream ⚫ It is a major type of lymphoma distinguished by the presence A. FUNCTIONS of Reed-Sternberg cells in lymph nodes. - A bilobed nucleus and prominent nucleoli often 1. Hemopoiesis resemble owl eyes 2. Source of lymphocytes ⚫ In contrast to Non-Hodgkin lymphoma, HD responds well to radiation and standard chemotherapy Figure 20. Reed-Sternberg Cell Figure 22. Red Bone Marrow Bone Marrow failure: cells did not mature, all are BLASTS around >20% blasts cells in patient complete blood count is suspicious of a starting BONE MARROW FAILURE (ex. LEUKEMIA) Page 7 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 ⚫ From BONE MARROW (immature T-Cells) —> migrate to VII. THYMUS THYMUS (maturation) —> populate the secondary lymphoid organs: TONSILS, SPLEEN etc. ⚫ Second primary organ ⚫ 4th week - endoderm of the 3rd pouch proliferates, builds ⚫ Located anteriorly to the mediastinum connective tissue of the stroma - epithelial reticulum ⚫ the primary or central lymphoid organ in which T cells are ⚫ 6th week - connective tissue which comes from the neural crest produced forms capsules and septas; thymic lobes ⚫ Endocrine, Immune System ⚫ 8-10th week - prothymocytes from the liver invade the thymus ⚫ Fibrous capsule gives off trabeculae (septa) that divide the ⚫ 12th week - cortex and medulla in the thymic lobes form gland into several lobules ⚫ 14-15th week - Hassal’s corpuscles secrete hormones; ⚫ Involution: lymphoid > adipose tissue maturation of the cell starts ⚫ Function: Antigen-independent maturation of T lymphocytes NOTE: maturation starts as early as embryo and at pubertal stage (also called thymocytes) most have involuted and doing their functions already - Epithelial reticular cells secrete thymosin and thymopoeitin ○ Induce T cell maturation and maintain cell- B. T CELL MATURATION - 2 SELECTION mediated immunity ⚫ Immature T lymphocytes migrate from bone marrow to the PROCESSES IN THE THYMUS: thymus to become mature lymphocytes. 1. Positive selection - permits the survival of only those T cells whose TCRs can recognize self-MHC molecule - If the cell cannot pass this test, due, for example, to faulty gene recombination and expression of α and β chains, they are nonfunctional and completely useless. Such cells (as many as 80% of the total) undergo apoptosis and are removed by the macrophages - MHC restriction 2. Negative selection - eliminates T cells that react too strongly with self-MHC plus self-peptide, survival depends on a cell not binding to MHC molecules with such peptides Figure 23. Thymus: chest x-ray showing a dotted line: enlarged - Self tolerance thymus which is normal but after the pubertal stage it will involute and be replaced by FATS ⚫ 98% of thermocytes die by apoptosis, it is expensive for the host. However, both processes are necessary to achieve MHC restriction and self-tolerance; Majority die of Apoptosis only 2% become mature and undergo the process of restriction and self- tolerance Figure 24. Thymus A. MATURATION PROCESS - Proliferation ⚫ Figure 25. Monograph of child and adult’s thymus - Rearrangement of TCR (T-cell receptor) genes ⚫ Vascularized connective tissue capsule that extends septa into - Acquisition of the surface receptors the parenchyma - Accessory molecules of the mature T cell ⚫ Lobule Almost all of the maturation occurs in the Thymus once the - Cortex - dark staining Immature T-lymphocytes passes ○ Thymocytes (T lymphoblast) ○ Associated with thymic epithelial cells (TEC) ⚫ At this stage, T cells with the ability to react with ‘self-antigens’ ○ Contains nodules; a deeper extension of cortex called (normal body components) are removed by apoptosis (or the paracortex which lacks nodules else autoimmune diseases will develop), creating a state of - Medulla - pain staining self-tolerance (body don’t fight against our own antigen) ○ Fewer, larger, more mature lymphocytes ⚫ Mature T cells then populate the secondary lymphoid organs and, from there, continuously recirculate via the bloodstream in the quest for antigen. Page 8 of 14 CMED 1EF  (006) HISTOLOGY OF THE IMMUNE SYSTEM AND THE LYMPHOID ORGANS DR. REFUERZO| 01/27/21 VIII. SPLEEN ⚫ 5 weeks mesoderm of dorsal mesentery builds stroma and capsule ⚫ 4 - 8 months (approximately 5 months) place of hematopoiesis ⚫ T and B lymphocytes enter spleen forming the white and red splenic pulp ⚫ a production site of antibodies and activated lymphocytes, which here are delivered directly into the blood ⚫ Responsible also for recycling iron to the bone marrow Figure 26. Thymus - Hassall’s corpuscles ⚫ Located high in the left upper quadrant of the abdomen and ⚫ The most characteristic microscopic feature of the thymic typically about 12 × 7 × 3 cm in size, the spleen’s volume varies medulla is the presence of thymic (Hassall’s) corpuscles with its content of blood and tends to decrease very slowly after formed by type VI epithelioreticular cell (TEC) puberty ⚫ Hassall’s corpuscles = location is on the Thymus ⚫ Secrete cytokines that regulate localized dendritic cells in the human thymus to induce CD4+ regulatory T cell development ⚫ Play a role in removing apoptotic thymocytes ⚫ PATHOLOGIC: if there is a persistence of Anterior mediastinal mass B. DiGEORGE SYNDROME (THYMIC APLASIA) ⚫ Rare congenital disorder ⚫ Failure of the thymus to develop properly ⚫ Defect chromosome 22 produced by a recombination error at meiosis, faulty development of the 3 rd and 4th pharyngeal pouches in the early embryo ⚫ Selective T cell deficiency: (because it happens initially during embryological stage) - Immunodeficiency with recurrent opportunistic infection - Malformations of the heart, esophagus, great vessels, and parathyroid glands - most die at early stage; Removal of Thymoma causes no Figure 28. Spleen differences because it is already suspicious of malignancy ⚫ Environmental risk factor: ⚫ Largest lymphatic organ (75-300grams) - Maternal alcohol consumption (1st trimester of pregnancy) - Encapsulated with fibrous capsules ⚫ Short stature, learning difficulties - Filters blood and reacts immunologically to blood-borne antigens, making it an important organ in defense against blood-borne antigens - Graveyard of RBC (120 days) - Hemopoeisis in fetal life ~5 months - Splenic ligaments (Avascular except the gastrosplenic ligaments (short gastric artery) ○ Portal hypertension (vascularized) ⚫ Blood reservoir able to store blood (~350mL) ⚫ Can constrict and pump blood into circulatory system if hemorrhaging - Self-transfusion (can squirt) 200mL into the blood in