HISTO_LC4_LYMPHATIC-SYSTEM.pdf

UNIVERSITY OF NORTHERN PHILIPPINES HISTOLOGY LC4 LYMPHATIC SYSTEM COLLEGE OF MEDICINE, BATCH 2026...

UNIVERSITY OF NORTHERN PHILIPPINES HISTOLOGY LC4 LYMPHATIC SYSTEM COLLEGE OF MEDICINE, BATCH 2026 Transcribers/Editors: Gadaza, P.N., Gascon S.M., Hierco F.A., Dr. Vivencio Refuerzo | Sept. 30, 2022 Lang-ayan, S.M. and Lalap, M.J. LYMPHATIC SYSTEM I. HISTORY II. LYMPHATIC SYSTEM DEVELOPMENT III. GENERAL FUNCTIONS OF THE LYMPHATIC SYSTEM IV. COMPONENTS OF THE LYMPHATIC SYSTEM V. ORGANIZATION OF THE LYMPHATIC VASCULAR TREE A. Unidirectional Lymphatic Vascular System B. Lymphatic Capillary C. Collecting Lymphatic Vessel D. Lymph Node E. Lymphovenous Valves VI. IMMUNE SYSTEM A. Components of the Immune System B. Types of Immune Response VII. ANTIBODIES VIII. LYMPHOCYTES A. B Lymphocyte B. T Lymphocyte C. MHC or HLA Complex D. Immune Response/ HLA Matching E. Other Cells IX. LYMPHATIC SYSTEM A. Lymphoid Nodules B. Lymph Node C. Thymus D. Mucosa-Associated Lymphoid Tissue E. Tonsils F. Peyer’s Patches G. Appendix H. Spleen III. General Functions of the Lymphatic System I. History 1. Returns fluid from tissues to the blood (2-4 liters of interstitial fluid/day) Lymphatic System- Integral part of the immune and circulatory system (prevention and resolution of edema approximately 3 liters a day) In 1627 - Gasparo Aselli coined the term “lymphatic system” 2. Returns large molecules to the blood (maintenance of interstitial fluid Hippocrates - reported “white blood” in the nodes. homeostasis) Aristotle - described fibers containing colorless fluid (lymph) observed between 3. Absorb and transport fats blood vessels and nerves. 4. Hemopoiesis - your liver, your bone marrow responsible for the production Science of Lymphology: Lymphatic Vascular Biology of stem cells later on o Early investigations of the anatomy and physiology of the lymphatic 5. Body defense/ immunity system, its function, and implications related to cancer have propelled Edema: swelling caused by excess fluid trapped in your body’s tissues technology and research to elucidate many of the enigmatic characteristics Hemopoiesis: production of blood cells and platelets. of the lymphatic system. IV. Components of the Lymphatic System o Recent research has implicated the lymphatic system in the pathogenesis Circulating of cardiovascular diseases including obesity and metabolic disease, lymphocytes dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial Lymph vessels infarction. *In cancer patients: Tumor Nodal Metastatic Staging- stage cancer based on the nodes; Central lymphoid the more positive the nodes are in histopathology report, the more aggressive the organs (primary): bone tumor (the more you are at Stage 3 or 4); node positivity for cancer patients connotes marrow and thymus poor prognosis and needs aggressive treatment. Peripheral lymphoid organs (secondary): II. Lymphatic System Development lymph nodes, spleen, Parallels that of blood structures tonsils, mucosa- Primordial lymphatic system: associated lymphoid o 6th week in the form of lymph sacs tissues (MALT) o 8th week: cisterna chyli- related portion of lymphatic system in the abdominocavity o 9th week: thoracic duct - communicating channels connecting the lymph Vascular Epithelial Growth Factor C or D: responsible for the maturation and proliferation of your lymphatic system 1 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo V. Organization of the Lymphatic Vascular Tree B. Lymphatic Capillary (30-80 μm) Lymphatic Vessels: found in almost every vascularized tissue except neural tissue Absorb interstitial solutes, and bone marrow macromolecules, and immune cells A. Unidirectional lymphatic vascular system that extravasate from the blood consists of: vascular system. 1. Lymphatic capillaries Extravasate: unintentional leakage of 2. Collecting lymphatic vessels vesicant fluids or medications from the 3. Lymph nodes vein into the surrounding tissues 4. Thoracic duct and right lymphatic trunk Lymph formation - facilitated by the discontinuous basement membrane It follows a unidirectional lymphatic flow from (red dashed line), and button-like lymphatic capillaries, collecting vessels, lymph nodes endothelial junctions allow passive for filtration, then to the major ducts then to your paracellular flow for lymph formation. subclavian. Very thin-walled channels which collect interstitial fluid from the tissue Factors that help in lymph flow spaces as lymph and return it to the blood. 1. Tissue fluid pressure 2. Contraction of surrounding muscle (exercise, massage, pneumatic Structural Features: compression) Lumen-filled with eosinophilic 3. Breathing movements (negative intrathoracic pressure) material (NO RBC - or else it 4. Rhythmic contraction of smooth muscle walls in vessel walls (pulsations of becomes a blood vessel) adjacent arteries) Partial basement membrane 5. Presence of valves which prevent backflow and not unsheathed by smooth muscles VI. Immune System Anchoring filaments tethering the interstitial matrix to General Plan of Drainage of Lymph: interstitial fluid Single layer of endothelium that are interconnected by discontinuous junctional structures known as “buttons” – very small tight junctions between endothelial cells. -Your lymphatic capillaries have a primary valve, a discontinuous basement membrane (the red one), and button-like epithelial junctions. -No smooth muscles and basement membrane because this is primary. Lymphatic capillaries are absent in: All avascular structures: Epidermis, Cornea, Nail, Hair, Cartilage Spleen and bone marrow Alveoli and respiratory bronchiole Brain and spinal cord C. Collecting Lymphatic Vessel Continuous junctional structures (zipper-like junctions; lymphatic valves) Contractile smooth muscle cells (SMCs): pumping force for lymph movement Right Lymphatic Duct: drains ⅓ of lymph in the body: enters near the Unidirectional propulsion of lymph confluence of the right subclavian vein and the right internal jugular vein Thoracic Duct: drains ⅔ of the lymph in the body: connects with the blood circulatory system near the junction of the left internal jugular vein with the left subclavian vein Electron microscope will show you a lined single endothelial cell and a lot of anchoring filaments in the interstitial matrix and interstitial fluids. 2 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo 2. Adaptive immune response specific defenses slower response, numerous memory cells o production of long-lived memory cells Two (2) specific responses: 1. Humoral immune response: o B cells, plasma cells, antibodies 2. Cell-mediated immune response: o Activation of phagocytes, antigen specific cytotoxic T cells, cytokines o (+) surface receptors for antigens D. Lymph Node 1. Cellular IR/ Cell-mediated IR Organization of lymph nodes with afferent lymphatic vessels and a single efferent Mediated by T Lymphocytes; provide immune protection without secreting lymphatic vessel. antibodies (They secrete cytokines to stimulate other cells of the body) 4 Afferent lymphatic vessels flow into the lymph node Immunocompetent cells react against and kill microorganisms, foreign cells and and virus-infected cells carry unfiltered lymph fluid 1 Efferent lymphatic vessel flow out of a lymph node T cells secrete cytokines: (+) other T cells, B cells, cytotoxic T cell and carry filtered lymph fluid Specificity is determined by small peptides associated with major Lymph’s passes through the components of your histocompatibility cells (MHC) in membrane APC lymph nodes and filtration happens most of the time Immunoglobulin-like receptor or T cells bind directly to foreign cells and and exits on your efferent lymphatic vessel induce: After that, it will pass through your thoracic duct o Cytotoxic killing o Secretion of signaling molecules (interleukins) that regulate immune E. Lymphovenous Valves response and activate macrophages and granulocytes Lymph drains into venous circulation through 4 distinct lymphovenous valves located where the Secretion of cytokines and interleukins to effect and stimulate the production of the internal jugular vein (IJV) and external jugular vein different antibodies from the plasma that differentiate from B cells (EJV) drain into the subclavian vein (SCV) Lymphovenous Valves (LVV) guards the junction 2. Humoral Immune Response: by regulating the flow of lymph to the veins and B cells, plasma cells, antibodies (B cells differentiate to plasma cells to form antibodies) prevents blood from entering the lymphatic system Related to the presence of circulating antibodies that bind to, inactivate or destroy specific foreign substances Functions: to protect organisms (body) from INVASION and DAMAGE by microorganisms Activation and proliferation of B cells against antigens requires the cooperation of (bacteria, virus) and foreign substances (antigen, protein molecules etc.) helper T cells: respond to the same antigen and secrete cytokines Specificity is determined by small molecular domains Components of the Immune System o Antigen has epitopes >>> taken by T helper cells>>>stimulate 1. Lymphoid Organs production of B lymphocytes >>> plasma cell produces antibodies bind Spleen, lymph nodes, tonsils, thymus, bone marrow to antigen 2. Nodules Epitope: the part of the antigen molecule to which an antibody attaches itself A network of reticular fibers and spherical, nonencapsulated aggregations of lymphocytes VII. Antibodies 3. Free Cells Lymphocytes, granulocytes, mononuclear phagocytes present in blood, lymph and connective tissue Plasma glycoproteins that interact 4. Antigen Presenting Cells (APC) specifically with antigen determinant In various tissues of the body heavily exposed to antigen (Langerhans that elicit their formation cell in epidermis) Signal other components of the immune system of the presence of Elaborate surveillance and defense by: foreign bodies 1. Monitoring body surfaces and internal fluid compartment Agglutinate cells or precipitate soluble 2. Having the ability to distinguish self from non-self antigen Otherwise, we produce autoimmune diseases (ex. SLE and Hashimoto’s Disease) or Bind antigen and start activating the different diseases that needs treatment (ruining your own body) complement system SLE (Systemic Lupus Erythematosus) - most common type of lupus Complement system - a system of proteins in blood plasma, mucus, and Hashimoto’s Disease - immune system creates antibodies that attack thyroid macrophages that react with bacterial surface components to aid removal of cells as if they were bacteria bacteria. 3. Reacting to presence of antigenic substances Basic structure of an immunoglobulin (antibody): Two light chains and two heavy chains linked by disulfide bonds. Types of Immune Response 1. Innate immune response First line of defense Phagocytic functions o Activation of phagocytes through cytokines Fast, nonspecific No memory cells 3 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Originate from precursor hemopoietic stem cells in the bone marrow that divide to give rise to an expanding population of uncommitted lymphocyte precursors and complete their differentiation either in bone marrow or thymus. Location: 1. Primary lymphoid organs B lymphocytes - leaves bone marrow as mature cell T lymphocytes - migrate to thymus to differentiate and mature 2. Secondary lymphoid organs Lymph nodes, spleen, lymphoid nodules B Lymphocyte Differentiate to plasma cell: antibodies Have immunoglobulin as integral membrane proteins o Membrane surface: antigen receptor complex Response of B cell to an antigen is more intense when APC’s (T helper Different functions and classes of antibodies cells), present the antigen-activated B cells T- helper cells secrete a cytokine (interleukin 2): MEMORY: QUICK RESPONSE o Induce proliferation and differentiation of antigen-activated Primary Response: B cells Antigen exposure -> stimulate B memory cells IgM (first antibody produced in React rapidly to second exposure initial immune response) o Memory lymphocytes are T Lymphocytes left behind after antigen T cells mature, differentiate, and acquire surface receptors and clearance immunocompetence in the thymus gland Secondary Exposure: o populate lymph nodes, the spleen, and lymphoid aggregates or Antigen exposure -> re- nodules in connective tissue. stimulates memory On encountering an antigen, T cells destroy the antigen either by cytotoxic lymphocytes (stimulate your action or by activating B cells when stimulated. IgG for faster effect) o Reactivation yields faster, After covid vaccination, you cannot determine if your antibody titer is good enough to more significant, better combat covid. After vaccination, they want to know the antibody titer for covid but the response problem is you cannot differentiate T lymphocyte or B lymphocyte. It doesn’t mean that o Antibodies have the capacity to neutralize, agglutinate, or precipitate the when you have low antibody titers for covid, you have no protection. Otherwise, there is o antigens from different viruses and bacteria. no guarantee that you will not be getting the infection Titer: laboratory test that measures the presence and number of antibodies in the blood TYPES OF T LYMPHOCYTES 1. Helper T cells (Th cells) Stimulate differentiation of B cells to plasma cells. Assist other lymphocytes by secreting immune chemicals called cytokines and interleukins o Cytokines - protein hormones that stimulate proliferation, secretion, differentiation, and maturation of B cells into plasma cells, which then produce Immune proteins called antibodies (Immunoglobulins/Ig) Characterized by CD4, coreceptor with the TCR (T-cell receptors) for binding CYTOKINES (in COVID-19): COVID-19 reacts to your ACE2 Receptors of your lungs, and stimulates production of cytokines Overstimulation and overproduction of your cytokine will lead to cytokine stored, and an excess is detrimental to the patient (thus, the need for anti-COVID drugs to control it) INTERFERONS: secreted from infected cells and activate innate immune response that promotes not only cytokine production but also natural killer VIII. Lymphocytes cell functions and antigen presentation Lymphoid Cells (Lymphocytes) Used as chemo drug for certain diseases like melanoma T and B lymphocytes Chief cellular constituent of lymphatic tissue 2. Cytotoxic T cells o Round, centrally placed nucleus Virus-infected cells, foreign cells, or malignant cells and destroy them. o Cytoplasm: lack specific granules with varying degrees of Activated in the presence of APC’s basophilia. Lysosomes with lytic granules that contain pore-forming protein o Release Perforins pore in the membrane of targeted cell ▪ Triggers apoptosis (programmed cell death) 4 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Bind antigens on virus-infected cells, foreign cells, or malignant cells and o (6 Ag match) destroy them Positive crossmatch shows that performed Abs are present, leading to Characterized by CD8 coreceptors hyperacute rejection. Cell-mediated immunity Even if you are matched, you need to undergo immune suppression, especially Activation of cytotoxic T cells also results in a population of memory for kidney transplant, which is very common in the Philippines cytotoxic T cells Importance of Immune Response/HLA Matching: o Cluster of genes whose products play important role in the 3. Memory T cells development of immune response and discrimination between self and rapid reaction to reintroduction of antigen non-self. long-living progeny of T cells o Determine whether a grafted tissue will be accepted as self activate the immune system and direct attack antigens (histocompatible) or rejected as non-self (histiincompatible) by the host 4. Regulatory (Suppressor) T cells Regulates (moderate or inhibit) immune response thru inhibiting action of helper and cytotoxic cells the check and balance of your immune system Your T lymphocytes stimulate different receptors. Your Th is restricted to MHC (major histocompatibility complex) and APC (antigen- presenting cells), your macrophages and they will now influence the cytokines from your Th cells to produce and activate your cytotoxic T lymphocytes and induce many parts of an inflammatory response Your cytotoxic T lymphocyte is restricted to CD8 and MHC class I antigen, and their Medical Application effect is to lyse or to undergo apoptosis or cell death to surface bacteria or antigen cells Types of Transplants 1. Autograft - self 2. Isograft - identical twins 3. Allograft - same species 4. Xenograft - different species What are immunosuppressants? Immunosuppressants (a.k.a Anti-Rejection Drugs): drugs or medicines that lower the body’s ability to reject a transplanted organ Medical application Two types of immunosuppressants: HIV cripples the patient’s immune system - by attacking the helper T cells 1. Induction Drugs: used at the time of transplant 2. Maintenance Drugs: used for the long term Susceptible to opportunistic infection AIDS - most common secondary immunodeficiency disorder Other Cells The CD4 is more associated within RBC 1. Antigen-presenting cells CD4 Normal Count for healthy adults and teens: 500 to 1,600 cells per cubic millimeter Phagocytose and process antigens, and then present the antigen to T cells, inducing their activation CD4 count of less than 200 is susceptible to produce infection (AIDS) Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) Complex Most antigen-presenting cells belong to the mononuclear phagocytic system. Cluster of genes located on short arm of chromosome (6pQ) Connective tissue macrophages Made from rER and Golgi apparatus Perisinusoidal macrophages in the liver (Kupffer cells) MHC (specialized integral membrane protein complexes on cell surface) -bind peptide fragments of foreign proteins for presentation to Langerhans cells in the skin antigen-specific T cells (helper and cytotoxic) Macrophages within lymphoid organs Cytotoxic T cells/CD8 + T cells: o MHC-I restricted 2. NK or Null cells or NON-T, NON-B LYMPHOCYTES Helper T cells/CD4 + T cells: 3rd type of lymphocyte o MHC-II restricted Genetically programmed to recognize and destroy altered cells Immune response/ HLA matching o First line defense against virally infected and cancer The immune response is the primary determinant of graft viability. cells to release perforin/ granzymes to act on the virus infected cells Human leukocyte antigen typing, for graft compatibility, is important for renal, lung, cardiac, and pancreatic matching Same as cytotoxic T cell functions Loci typed are HLA-A, -B and -DR Natural Killer (NK) Cells Part of the innate and adaptive immunity 5 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Destroys unhealthy host cells, including those infected with virus Parts of the secondary lymphoid nodules: or bacteria, and potentially tumorigenic cells Dark region: mantles/marginal zone Large granular lymphocytes Dark-staining nuclei, condensed chromatin, and little or no Azurophilic granules cytoplasm Direct lysis Lymphocytes contained within cellular framework of stellate cells o Not mediated by an immune response consists of smaller and mature lymphocytes o MHC - unrestricted Light region: germinal center o Does not involve an antigen antibody interaction Cells are more loosely aggregated and the developing lymphocytes have larger and lighter-staining nuclei with more cytoplasm “lymphoblast” Contains less mature lymphocytes undergoing mitotic division (active site of lymphocyte proliferation) IX. Lymphatic System Lymph node Diffuse lymphoid tissue Small bean shaped (coffee beans) encapsulated organs Found in the internodal, deep cortical and medullary regions of lymph nodes, Capsule: LCT traversed by lymphatic sinuses periarterial lymphoid sheaths (PALS) of spleen, internodal region of the Functions: tonsils, Peyer’s patches Sponge-like stroma with lymphocytes in its meshes Lymph filtration and phagocytosis of bacteria or foreign substances from lymph Stroma is made up of reticular fibers and cells of mesenchymal origin Reticular cells appear elongate or stellate elements with ovoid euchromatic It produces, store, and recirculate B cells and T cells nucleus and scant acidophilic cytoplasm B cells congregate in the lymphatic nodules of lymph nodes Free cells are also present (lymphocytes, plasma cells and macrophages) T cells are concentrated below the nodules in the deep cortical or paracortical regions Lymphoid Nodules (Lymphoid follicles) Sites of antigenic recognition and antigenic activation of B cells, Circumscribed closely packed collection of lymphocytes within areas of which give rise to plasma cells and memory B cells diffuse lymphoid tissue The structure has 4 afferent and 1 efferent vessel Not encapsulated Found in the cortex of lymph nodes, periphery of white pulp of spleen and lamina propia of GIT and RT Numerous in tonsils, Peyer’s patches and appendix NONE in the thymus Types of Lymphoid Nodules 1. Primary lymphoid nodule/follicle (inactive) Lack the light-staining germinal centers Small immature B lymphocytes; closely packed and disorganized Difficult to see in light microscope 2. Secondary nodules Most common, primary become secondary nodules Pale staining central portion: germinal center Site of B lymphocyte proliferation and differentiation to plasma cells following initial or secondary exposure to antigen B cells predominate in nodules T cells are abundant in adjacent areas 6 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo 1. Lymph cortex: Parenchyma supported by reticular fibers and associated reticular cells High concentration of lymphocytes B and T cells enter the LNs through the HEV in the paracortex The inner is populated with T lymphocytes, and the outer with B Lined by tall cuboidal or columnar endothelium lymphocytes Specialized lymphocyte-homing receptors mesh filled with lymphocytes, plasma cells and macrophages present on the following: all parts of the GI tract Absent in the spleen Parts: o Outer cortex Circulating lymphocytes recognize the receptors in the endothelial cells and o B lymphocytes; 1° and 2° lymph nodules leave the bloodstream to enter the lymph node o Inner (paracortex) Peyer’s patches in the small intestines, tonsils, appendix, and cortex of the o Diffuse lymphatic tissues thymus: present o Populated with T lymphocytes High endothelial venules are absent from the spleen ▪ Enter the lymph nodes through the specialized post capillary venules 2. Lymph sinus (sinuses are the supporting caps) (HEV’s) Lined with incomplete squamous epithelial cells with lumen bridged by Loosely packed cells meshwork of stellate reticular cell connected with each other and to walls of Cortex: B cells sinus via slender processes 1. Primary nodules: packed B cell, Ag+ 1. capsular/ subscapular/ marginal 2. Secondary nodules: ▪ Inverted bowl-shaped cavity which separates capsule o GC with mantle zone from cortical parenchyma o Site of B cell proliferation 2. trabeculae/ intermediate/ cortical Paracortex: T cells ▪ Sinus which penetrates parenchyma along with Antigen-dependent T cell - differentiation and proliferation trabeculae medullary HEVs (High Endothelial Venules) - facilitate rapid translocation of ▪ Large tortuous irregular channels that branch and lymphocytes from blood into lymphoid tissue anastomose repeatedly dividing parenchyma into medullary cords Unilateral flow Afferent lymphatic vessel > marginal/ subcapsular sinus > medullary sinus > marginal sinus at the hilum > efferent lymphatic vessels in hilum 7 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo 3. Medulla * The central region of the lymph node is the lighter-staining medulla A. Dark-staining medullary cords B. Light-staining lymphatic channels, the medullary sinuses (main channels) 4.Blood Vessels nearly all enter the hilus larger arterial branches initially running trabeculae enter medullary cords before returning to the cortex where they supply capillary plexuses of diffuse lymphoid tissue Thymus Bilobed organ located in superior mediastinum anterior to the great vessels as they merge from the heart Extends from the root of the neck to the pericardial sac Develops from the endoderm of the 3rd and 4th pharyngeal pouches. Lymphocytes arise from mesenchyme 1st organ to become lymphoid during embryonic life o T cells: site of differentiation and maturation. Medulla Adipose tissue, accumulation of adipose cells in between Medullary Cords Fibrous capsule gives off trabeculae (septa) that passes through the medulla dark staining Subdivided the gland into incomplete lobules Branched cordlike masses of lymphoid tissue extending from the paracortex Each lobule consists: 1. Cortex. T and B lymphocytes, plasma cells o Dark staining o Thymic lymphocytes: dark due to dense aggregations Medullary sinuses that do not form thymic nodules. light staining lymphatic link channels. - T. Lymphoblast, macrophages, thymic epithelial Dilated spaces lined by discontinuous endothelium that separate the cells (TEC) medullary cords. Thymus have no lymphatic nodules, what they have Final lymph filter before they pass through the efferent lymphatic vessels. are thymic lymphocytes: lymphoblast, macrophages, The blood supply, the arteries and veins, supplies your B and T lymphocyte and thymic epithelial cells. from the lymphatic nodules 2. Medulla Cortical sinuses converge at the hilum as the efferent lymphatic vessel. o Light staining o Only a few lymphocytes but more epithelial reticular cells. o Thymic (Hassall’s) corpuscles- oval structures with round or spherical aggregations (whorls) of flattened epithelial cells. - It exhibits degeneration centers that stain pink or eosinophilic. Blood vessels and adipose cells Pass into the thymus gland via the connective tissue capsule and the trabeculae. 8 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Histology of thymus gland Secrete several cytokines that control activity of local dendritic cells including factors that promote development of regulatory T cells for peripheral tolerance. Most active and prominent before puberty and undergoes involution with less activity in adult. o Lymphocyte production declines, and thymic (Hassall’s) corpuscles become more prominent. o Parenchyma or cellular portion: Blood thymus barrier ▪ Replaced by loose connective tissue and adipose cells. Prevent developing lymphocytes from exposure to blood-borne antigens Thymic cortex Macrophages outside of the capillaries ensure that substances transported in Epithelial reticular cells (thymic nurse cells) the blood vessels do not interact with the developing T cells in the cortex and o Large euchromatic nuclei but are morphologically and functionally induce an autoimmune response against the body’s own cells or tissues diverse. o Surround the lymphocytes and promote their differentiation After maturation, the T cells leave the thymus gland via the bloodstream and populate proliferation and maturation the lymph nodes, spleen and other thymus dependent lymphatic tissues in the 1. Immunocompetent T cells organism. 2. Helper T Cells 3. Cytotoxic T cells o Acquire their surface receptors for recognition of antigens Functions: 1. Cytokine secretions 2. Compartmentalize the thymus into a cortex and a medulla 3. Part of the blood-thymus barrier The three major types 1. Squamous TEC form blood thymus barrier 2. Stellate TECs form cytoreticulum o considered ENDOCRINE GLAND that is why thymus is considered an endocrine gland because it secretes cytokines, interleukins and even thymosin and thymine to act their own functions later on. a. APs with MHC I and II b. Cytokines for T-Cell development and other immune functions 3. Squamous cortical TECs with MHC II. Role of Thymus in T-Cell Maturation and Selection o Functional corticomedullary barrier between each lobule Thymocytes begin a stringent, two-stage selection process of quality control, which ensures that mature T cells have TCRs that are fully functional but do Thymus (Medulla) not recognize and strongly bind MHC with self-antigens. Three types of medulla TECS 1. Second layer of the boundary of medulla and cortex Selection process: Pre-T lymphocytes begins in the cortex, ends in medulla, and lasts 2. Cytoreticulum about 2 weeks. From 98% of T-lymphocytes, only 2% become functional (populate 1. Supports T lymphocytes, dendritic cells, and macrophages secondary point organs later on) 2. Expresses many specialized proteins specific to cells of other organs Positive Selection: occurs in the thymic cortex and allows survival only of T cells with 3. Large aggregrates of TECs (“Hassall” corpuscles)- the most common, when functional TCRs that recognize MHC class I and class II molecules. It relates to the you see strong spherical aggregation, that’s the thymic medulla. This will antigen presenting cells MHC I and II. If it binds to MHC Class, it will survive and degenerate into adipose tissue later on. advance to the medulla. 9 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Negative selection: occurs in the medulla, and only T-cells that do not tightly bind self- Loss of T-cell-mediated immunity due to loss of thymus antigen presented on the dendritic cells. In thymic medulla the question will be if it binds to antigen, if no you proceed to Different anomalies become immunocompetent in self antigen or else, you’ll have autoimmunity problems, Short stature, learning difficulties if yes you die of apoptosis Mnemonic (CATCH 22) If the T cells recognize the self as an antigen it would lead to autoimmune problems C Cardiac abnormalities (Tetralogy of Fallot) A Abnormal facies T Thymic aplasia C Cleft palate H Hypocalcemia (due to hypoplasia of lack parathyroids) 22 22q11 deletion Bone Marrow- site of most of the stem cells, the different cells of the body. Red Bone Marrow Soft, loosely organized, highly vascular material separated from osseous tissue by endosteum of the bone o Vertebrae, ribs, sternum, cranium, ends of humerus/femur As blood cells mature, they push their way through the reticular and endothelial cells to enter the sinusoids and flow away in the bloodstream Functions o Hemopoiesis o Source of lymphocytes Thymus Mucosa-Associated Lymphoid Tissue (MALT) Involutes after puberty, replaced by adipose tissue, production of T cells Comprises the GIT, respiratory, GUT, mucosal lining of the urinary tract. decreased. o Large and diffuse collections of lymphocytes T lymphocytes progeny is established, immunity is maintained without new T o IgA-secreting plasma cells cell production Clinical Correlation: DiGeorge Syndrome (Thymic Aplasia) o APCs o Lymphoid nodules One of the largest lymphoid organs containing up to 70% of all the body’s immune cells (B cells, Helper T cells). Most of the immune cells in MALT are dispersed diffusely in the connective tissue; others are found in aggregates that form large, conspicuous sutures such as the tonsils, the Peyer’s patches in the ileum, and the appendix. DiGeorge Syndrome (Thymic Aplasia) Failure of development of the third and fourth pharyngeal pouches. Patient has short stature and difficult in learning activities Absence of the parathyroid glands and the thymus 10 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Lingual tonsils Tonsils o Surface of the posterior third of the tongue. Large, Irregular masses of lymphoid tissue in the mucosa of the posterior oral o Stratified squamous epithelium cavity and nasopharynx. o Lack distinct capsules. Late puberty: progressive atrophy o Each tonsil has single crypt; not branching crypts Blood supply: tonsillar branch of the facial artery o If you see salivary glands, you are at the base of the tongue and Venous drainage: it’s the lingual tonsil. o the paratonsillar vein descends from the soft palate across the lateral aspect of the tonsillar capsule o It is nearly always divided in tonsillectomy and may give rise to troublesome hemorrhage Lymphatic drainage: 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 Pharyngeal tonsil (single) o Single medial mass situates in the posterior wall of pseudostratified ciliated columnar epithelium of the nasopharynx. o Adenoid o Thin capsule o Pharynx: part of the respiratory system ▪ The mucosa with diffuse lymphoid tissue and nodules (B cells, T cells) is invaginated with shallow infoldings but lack crypts. Medical application We have five tonsils: Inflammation of the tonsils – Tonsilitis – more common in children than 3 palatine tonsil adults o Two (2) large ovoid accumulations of lymphoid tissue beneath the Chronic inflammation of the pharyngeal lymphoid tissue and tonsils of mucous membrane. children often produces hyperplasia and enlargement of the tonsils to form o Posteriorly on the soft palate “adenoids”, which can obstruct the eustachian tube and lead to middle ear o Stratified squamous nonkeratinized epithelium infections. o 10-20 deep invaginations or tonsillar crypts in which epithelial lining is densely infiltrated with lymphocytes and other leukocytes ▪ The lymphoid tissue is filled diffusely with lymphocytes, with many secondary lymphoid nodules around the crypts. o Partially encapsulated: (+) dense connective tissue. ▪ Acts as barrier for spreading tonsillar infection 11 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Clinical Correlation: Tonsillectomy - procedure of removal of the tonsils, You have to Spleen ligate the blood supply in the facial artery or there will be (...) bleeding after surgery. Largest lymphatic organ (75-300 gms) Treatment is antibiotic first. Encapsulated with fibrous capsule Peyer’s patches Filters blood and reacts immunologically to blood-borne antigens Aggregations of lymphatic nodules (T and B lymphocytes) in the wall of the Graveyard of RBC (120 days) ileum which allow close monitoring of the microorganisms in the gut Hemopoiesis in fetal life – 5 months Located in the distal ileum Splenic ligaments (avascular) except gastrosplenic ligaments (short gastric artery) Present in the GI tract: Antigen-presenting cells - Although the spleen performs various important functions in the In contact with pathogen: present to T-helper cells body, it is not essential organ for life Lymphocytes Your antibodies in GI are IgA to combat your antigen. Encapsulated with trabeculae White pulp 20% of the spleen Lymphoid nodules and the periarteriolar lymphoid sheaths (PALS) Red pulp Blood-filled sinusoids and splenic cords Blood Flow Closed circulation: passing directly into splenic sinuses In the closed circulation, capillaries branching from the penicillar arterioles connect directly to the sinusoids and the blood is always enclosed by endothelium Open circulation: being dumped from the vasculature into the lymphoid tissue of the red pulp’s splenic cords Capillaries from about half of the penicillar arterioles are uniquely open- ended, dumping blood into the stroma of the splenic cords. In this route plasma and all the formed elements of blood must reenter the vasculature by passing through narrow slits between the stave cells into the sinusoids Stiff or effete, swollen RBCs at their normal life span of 120 days are blocked from passing between the stave cells and undergo selective removal by macrophages Appendix A blind evagination off the cecum, the appendix is a significant part of the White Pulp MALT with its lamina propria and submucosa filled with lymphocytes and Immune component of the spleen lymphoid follicles o Lymphatic tissue It is a vestigial organ; dispensable; a lot of lymphoid follicles o Lymphatic cells that surround the central arteries of the white pulp are primarily T cells o Lymphatic nodules mainly B cells o APCs and macrophages ▪ Detect trapped bacteria and antigens and initiate immune responses against them Macrophages in the spleen also break down hemoglobin of worn-out erythrocytes Iron Recycled 12 [HISTOLOGY] 1.04 LYMPHATIC SYSTEM – Dr. Vivencio Refuerzo Red Pulp 1. Splenic Cords (of Billroth) 2. Splenic sinusoids Elongated endothelial cells called stave cells line these sinusoids Allow separation of healthy from effete red blood cells in the splenic cords Functions: o Blood filtration in the open circulation involves interaction with splenic cord macrophages that remove old, swollen RBCs unable to slip between stave cells to reenter the venous blood flow o Graveyard of RBCs and recycling or iron for erythropoiesis Medical Applications After splenectomy (surgical removal of the spleen, from trauma, certain diseases like cancer, etc.), the number of abnormal erythrocytes in the circulation increases although most such cells are then removed by macrophages in sinusoids of the bone marrow and liver. Trauma: relatively thin capsule Splenomegaly: Lymphoma or other malignant growth, infections such as mononucleosis, or sickle cell disease and other types of anemia Post splenectomy: OPSI o Susceptible: encapsulated organisms, especially H. influenza, S.pneumonia, and meningococci o Properdin helps initiate the alternative pathway of complement activation, which is particularly useful for fighting encapsulated organisms o Tuftsin enhances the phagocytic activity of PMNs and macrophages We do vaccination before surgery to prevent OPSI complications Only occurs in about 1-5% of cases, but there is high mortality Emergency trauma in need of surgery: 2 weeks after surgery 13