Histology LC 3: Immune System and Lymphoid Organs PDF

○ Found in various tissues exposed to antigens DISCUSSION OUTLINE (e.g., Langerhans cells in the epidermis) I. IMMUNE SYSTEM Types of...

○ Found in various tissues exposed to antigens DISCUSSION OUTLINE (e.g., Langerhans cells in the epidermis) I. IMMUNE SYSTEM Types of Immune Response Types of Adaptive Immune Monitors body surfaces and internal fluid Response compartments II. CYTOKINES Having the ability to distinguish self from non-self III. ANTIGENS AND ANTIBODIES Reacting to the presence of antigenic substances Classes of Antibodies Actions of Antibodies IV. ANTIGEN PRESENTATION V. IMMUNE RESPONSE/ HLA MATCHING VI. CELLS OF ADAPTIVE IMMUNITY Innate Immune Response ○ First Line of Defense; physical barriers (skin and Antigen-Presenting Cells mucous membranes of the GIT,respiratory and Lymphocytes urogenital tracts) T Lymphocytes ○ Key Cells: NK Cells - Neutrophils B Lymphocytes - Toll-like receptors on leukocytes VII. LYMPHATIC SYSTEM - Natural killer cells Types of Lymphoid Nodules - Leukocytes: antimicrobial chemicals (HCL, Secondary Lymphoid Nodule Defensins, lysozyme, complement, interferons) VIII. LYMPH NODES ○ Phagocytic Functions: - Activation of phagocytes via cytokines IX. THYMUS ○ Fast, nonspecific X. MUCOSA-ASSOCIATED LYMPHOID ○ No memory cells TISSUE Tonsils Adaptive Immune Response Peyer’s Patches ○ Acquired by exposure to microorganism Appendix ○ Key Cells: XI. SPLEEN - B cells and T cells (attacks specific invaders White Pulp presented by APCs) Red Pulp ○ Slower, specific defenses ○ Rapid response of same invader ○ Long-lived memory cells Function is to protect the body from invasion and damage by microorganisms (e.g., bacteria, viruses, Cellular Immune Response (Cell-mediated Immune parasites) and foreign substances (antigens, protein Response) molecules, etc) ○ Mediated by T lymphocytes; provide immune protection w/out secreting antibodies ○ Immunocompetent cells react against and kill microorganisms, foreign cells and virus-infected. cells Lymphoid Organs ○ T cells secrete cytokines: (+) T cells, B cells, ○ Central (Primary) lymphoid organs: bone marrow cytotoxic T cell and thymus ○ Specificity is determined by small peptides ○ Peripheral (Secondary) lymphoid organs: lymph associated with major histocompatibility cells nodes, spleen, tonsils, mucosa-associated (MHC) in membrane antigen-presenting cells lymphoid tissues (APC) Lymphoid nodules ○ Immunoglobulin-like receptor or T cells bind ○ Network of reticular fibers and non-encapsulated directly to foreign cells and induce: lymphocytes - Cytotoxic killing Free cells - Secretion of signaling molecules (interleukins) ○ Lymphocytes,granulocytes, mononuclear that regulate immune response and activate phagocytes: Present in blood, lymph, and macrophages and granulocytes connective tissue Humoral Immune Response Antigen Presenting Cells (APCs) ○ Mediated by B cells, plasma cells, and antibodies BATCH 2028 1C. 1 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. ○ Related to the presence of circulating antibodies that bind to, inactivate or destroy specific foreign substances ○ Antibodies produced by plasma cells derived from B lymphocytes ○ Activation and proliferation of B cells against antigens requires the cooperation of helper T cells ○ Respond to the same antigen and secrete cytokines ○ Specificity is determined by small molecular domains: - antigen has epitopes taken by T helper cells which stimulate production of B lymphocytes and eventually plasma cell which produce antibodies bind to antigen ANTIGENS A molecule that is recognized by cells of the adaptive immune system ○ Soluble molecules (such as proteins or polysaccharides) or molecules that are still components of intact cells (bacteria, protozoa, or tumor cells). Immune cells recognize and react to small molecular domains of the antigen known as antigenic determinants or epitopes. Immune response to antigens may be cellular, humoral or both. ANTIBODIES Plasma glycoproteins that interact specifically with antigen determinants that elicit their formation. Diverse group of peptides and glycoproteins, with Signal other components of the immune system of paracrine mode of action. the presence of foreign bodies ○ Coordinate cell activities in the innate and Agglutinate cells or precipitate soluble antigen adaptive immune responses during tissue injury Bind antigen and start activating the complement or inflammation system Major responses induced in target cells: ○ Chemotaxis: directed cell movement at sites of Basic Structure of the Antibody inflammation (diapedesis): chemokines ○ Increased mitotic activity ○ (+/-) of lymphocytes activities (adaptive immune response) : interleukins ○ (+) phagocytosis or direct cell killing by innate immunity BATCH 2028 1C 2 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) Complex ○ Cluster of genes located on short arm of chromosome 6 (6pQ) ○ Made from RER and golgi apparatus ○ MHC (Specialized integral membrane protein complexes on cell surfaces) - Bind peptide fragments of foreign proteins for presentation to antigen-specific T cells (helper and cytotoxic) T lymphocytes are specialized to recognize both classes of MHC proteins and the antigens they present. MHC Class I: all nucleated cells “self-antigens”: spared by T cells Memory : quick response Long lived cells - Virally infected cells, or altered by gene Primary response: Ag+ exposure mutation: elimination process - Memory lymphocytes are left behind after Ag+ MHC Class II: synthesized and transport to cell clearance surface by the mononuclear phagocyte system A second exposure to the same Ag+ re-stimulates memory lymphocytes - Reactivation yields faster, more significant, better response The immune response is the primary determinant of graft viability. Human leukocyte antigen typing, for graft compatibility, is important for renal, lung, cardiac, and pancreatic matching Loci typed are HLA-A, B-, and- DR (6 Ag match) Positive cross-match shows that performed Abs are present, leading to hyperacute rejection. IMPORTANCE: Cluster of genes whose products play an important role in the development of immune response and discrimination between self and non-self. Determine whether a grafted tissue will be accepted as self (histocompatible) or rejected as non-self (histoincompatible) MEDICAL APPLICATION —> Important in transplants TYPES OF TRANSPLANT 1. Autograft - self 2. Isograft - between identical twins 3. Homograft or allograft - between the same species → Administer immunosuppressants : patient will become prone to opportunistic infections/ cancer Q: What are immunosuppressants? → Immunosuppressants are drugs or medicines that lower the body’s ability to reject a transplanted organ. Another term for these drugs is anti-rejection drugs 4. Xenografts - between different species BATCH 2028 1C 3  HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. A. ANTIGEN PRESENTING CELLS - T cells mature, differentiate, and acquire surface - most antigen-presenting cells belong to the receptors and immunocompetence in the thymus gland mononuclear phagocytic system - Populate lymph nodes, the spleen, and lymphoid - phagocytose and process antigens, and then aggregates or nodules in connective tissue. present the antigen to T cells, inducing their - On encountering an antigen, T cells destroy the antigen activation either by cytotoxic action or by activating B cells when - active endocytic system and express MHC Class II stimulated. Connective tissue macrophages perisinusoidal macrophages in the liver TYPES OF T LYMPHOCYTES: (Kupffer cells), A. Helper T cells Langerhans (dendritic) cells in the skin, - stimulate differentiation of B cells to plasma cells macrophages within lymphoid organs - assist other lymphocytes by secreting immune chemicals called cytokines, (interleukins) B. LYMPHOID CELLS: T Lymphocytes and B - long-lived memory helper T cells, which allow a Lymphocytes more rapid response if the antigen appears - Chief cellular constituent of lymphatic tissue again later. (Memory T cells) – Round, centrally placed nucleus B. Cytotoxic T cells – Cytoplasm: lack specific granules with varying - virus-infected cells, foreign cells, malignant cells degrees of basophilia - activated in the presence of APC’s - Originate from precursor hematopoietic stem - CD8 : MHC I w/ interleukin -2 cells in the red bone marrow that divide to give - lysosomes w/ lytic granules than contain rise to an expanding population of uncommitted pore-forming protein: Perforins lymphocyte precursors and complete their → Perforins: form pores in the membrane of differentiation either in bone marrow (B cells) or targeted cell which will trigger apoptosis thymus (T cells) → apoptosis - programmed cell death C. Regulator (Suppressor) T cells - CD4+, CD25+ and serve to inhibit specific immune Location: - Presence of Foxp3 transcription factor, play A. Primary Lymphoid Organs crucial roles in allowing immune tolerance 1. B lymphocytes - Maintains unresponsiveness to self-antigens - leaves bone marrow as mature cell and suppresses excessive immune responses. - some remain and differentiate further in the - cells produce peripheral tolerance, which acts to bone marrow supplement the central tolerance that develops 2. T lymphocytes in the thymus. - migrate to thymus to differentiate and mature D. γδ T lymphocytes - Migrate to the epidermis and mucosal epithelia, B. Secondary Lymphoid Organs intraepithelial 1. Mucosa-Associated Lymphoid Tissue (MALT) - They function in many ways like cells of innate 2. Spleen immunity ,in the front lines against invading 3. Lymphoid nodules microorganisms. Approximate Percentages of B Cells and T Cells in the Lymphoid Organs Lymphoid T cell % B cell % Organs Thymus 100 0 Bone Marrow 10 90 Spleen 45 55 Lymph Node 60 40 Blood 70 30 BATCH 2028 1C 4 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. ○ Not encapsulated MEDICAL APPLICATION ○ Found in the cortex of lymph nodes, periphery of → HIV cripples the patient's immune system by white pulp of spleen and lamina propria of the gastrointestinal tract (GIT) and respiratory tract attacking the helper T cells → decrease in CD4+ T cells (RT) which will make them susceptible to opportunistic ○ Numerous in tonsils, Peyers’ patches and infection. appendix ○ None in thymus - 3rd type of lymphocytes - Genetically programmed to recognize and destroy 1. Primary Lymphoid Nodule altered cells which include ○ Lack the light-staining germinal centers → virally infected cells ○ Small, immature B lymphocytes; aggregates of → cancer cells uniform cell density and staining - Same as cytotoxic T cells in functions ○ Difficult to see in light microscope 2. Secondary Nodules ○ Most common ○ Primary becomes secondary nodules B Lymphocytes ○ Larger, more eurochromatic cells centrally ○ Differentiate to plasma cell : antibodies ○ Pale-staining central portion is the germinal ○ Immunoglobulin as integral membrane proteins center Membrane surface receptors (IgM/IgD): ○ Site of B lymphocyte proliferation and antigen receptor complex differentiation to plasma cells following initial or ○ Response of B cell to an antigen is more intense secondary exposure to antigen with T helper cells T helper cells secrete a cytokine (interleukin 3. B Cells predominate in nodules 2), which induces proliferation and differentiation of antigen-activated 4. T Cells are abundant in adjacent areas B Memory Cells ○ React rapidly to second exposure PARTS Dark Region: Mantle/Marginal Zone ○ Dark-staining nuclei, condensed chromatin, and little or no cytoplasm ○ Lymphocytes contained within a cellular framework of stellate cells consists of smaller and mature lymphocytes Light Region: Germinal Center ○ 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 of lymphocyte proliferation) A. Diffuse Lymphoid Tissue ○ Found in the internodal, deep cortical and medullary regions of lymph nodes, periarterial lymphoid sheaths (PALS) of spleen, internodal regions of tonsils, and peyers’ patches ○ Sponge-like stroma made up of reticular fibers and cells of mesenchymal origin with lymphocytes in its meshes ○ Reticular cells appear elongate or stellate elements with ovoid euchromatic nucleus and scant acidophilic cytoplasm ○ Free cells are also present (lymphocytes, plasma cells and macrophages) B. Lymphoid Nodules (Lymphoid Follicles) ○ Circumscribed closely packed collection of lymphocytes within areas of diffuse lymphoid tissue BATCH 2028 1C 5 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. LYMPHOID NODULES 3 MAJOR REGIONS Rapid proliferation of activated B lymphoblasts in 1. Cortex - contains B Cells the germinal center causes smaller, naive a. Primary Nodules containing packed B cells and lymphocytes to be pushed aside and crowded Ag + together peripherally as the follicular mantle (M) b. Secondary Nodules - GC with mantle zone, which is the site of B cell proliferation 2. Paracortex - contains T cells a. Antigen-dependent T cells for differentiation and proliferation b. HEVs for facilitating rapid translocation of lymphocytes from blood into the lymphoid tissue 3. Central Medulla Small bean shaped encapsulated organs ○ Capsule: LCT traversed by lymphatic sinuses ○ 400-500 lymph nodes Functions ○ Lymph filtration and phagocytosis of bacteria or foreign substances from the lymph ○ It produces, stores, and recirculates B cells and T cells B cells congregate in the lymphatic nodules of lymph nodes T cells are concentrated below the nodules in the deep cortical or paracortical regions ○ Sites of antigenic recognition and antigenic activation of B cells, which give rise to plasma cells and memory B cells 1. Lymph Cortex ○ Parenchyma supported by reticular fibers and associated reticular cells ○ Contains high concentration of lymphocytes ○ Mesh filled with lymphocytes, plasma cells, and macrophages ○ Parts Outer cortex - B lymphocytes, primary and secondary lymph nodules Inner (Paracortex) BATCH 2028 1C 6 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. Diffuse lymphatic tissues A. Dark-staining medullary cords : branched Populated with T lymphocytes, which cordlike masses of lymphoid tissue extending from enters the lymph nodes through the the paracortex specialized post capillary venules (HEV’s) B and T cells, plasma cells B. Light-staining lymphatic channels, the medullary sinuses dilated spaces lined by discontinuous endothelium that separate the medullary cords. ○ B and T cells enter the lymph nodes through the HEV in the paracortex ○ Lined by tall cuboidal or columnar endothelium Specialized lymphocyte-homing receptors Sites of entry by diapedesis of lymphocytes to the lymph nodes Medullary cords Circulating lymphocytes recognize the are branched cordlike masses receptors in the endothelial cells and leave the of lymphoid tissue extending from the bloodstream to enter the lymph node paracortex. ○ Peyers’ patches in the small intestine, tonsils, T&Blymphocytes, plasma cells appendix, and cortex of the thymus are present Medullary sinuses ○ Absent in the spleen dilated spaces lined by discon- tinuous endothelium that separate 2. Lymph Sinus ○ Lined by a very thin, discontinuous endothelium The medullary cords: penetrated by reticulin fibers and processes of final lymph filter dendritic cells cortical sinuses and converge at the hilum as Capsular/subcapsular or marginal sinus - the efferent lymphatic vessel inverted bowl shaped cavity which separates capsule from cortical parenchyma Trabeculae/intermediate/cortical - sinus which penetrates parenchyma along with the trabeculae medullary 3. Lymphoid Nodules ○ Formed largely by helper T lymphocytes and proliferating B lymphoblasts Unilateral Flow Afferent Lymphatic Vessels → Marginal/Subcapsular Sinus → Trabecular Sinus → Medullary Sinus → Marginal Sinus → Marginal Sinus at the Hilum → Efferent Lymphatic Vessels 4. Medulla The central region of the lymph node is the lighter-staining medulla. BATCH 2028 1C 7 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. -Larger arterial branches initially running with Histology of Lymph Nodes trabeculae enter medullary cords before returning to the cortex where they supply capillary plexuses of diffuse lymphoid tissue Medical Application A low-magnification section of a lymph node shows the three functional regions: the cortex (C), the paracortex (P), and the medulla (M). Connective tissue of the capsule (CT) completely surrounds each lymph Metastatic cancer cells node and extends as several trabeculae (T) throughout the lymphoid Lymphatic route : SLN tissue. Major spaces for lymph flow are present in this tissue under the capsule and along the trabeculae. A changing population of immune cells is suspended on reticular fibers throughout the cortex, paracortex, and Lymphoma : Neoplastic proliferation of lymphocytes medulla. Lymphoid nodules (LN) are normally restricted to the cortex, and Lymphadenopathy : obliterated normal the medulla is characterized by sinuses (MS) and cords (MC) of lymphoid architecture tissue. * enlarged, encapsulated structure filled with lymphocytes The outer regions on the convex sides of a lymph node include the capsule (C), subcapsular sinuses (S), and dif- fuse lymphoid tissue with lymphoid nodules (N). Afferent lymphatic vessels (which are only rarely shown well in sections) penetrate this capsule, dumping lymph into the sinus where its contents are processed by lymphocytes and APCs. 5. Blood Vessels -Nearly all enter hilus BATCH 2028 1C 8 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. pass into the thymus gland via the connective tissue capsule and the trabeculae A. THYMUS CORTEX - Bilobed organ located in superior mediastinum Darker-stained anterior to the great vessels as they emerge Thymic lymphocytes dense from the heart aggregates: T lymphoblast, - Extends from the root of the neck to the macrophages, thymic epithelial cells pericardial sac (TEC) - Develops from the endoderm of the 3rd and 4th No lymphatic nodules pharyngeal pouches ❖ Thymic Cortex - 1st organ to become lymphoid during embryonic Epithelial reticular cells/ Thymic life nurse cells T cells: site of differentiation and - surround the lymphocytes and maturation promote their differentiation, proliferation, and maturation Histology of thymus gland 1. immunocompetent T Most active and prominent before puberty and undergoes cells involution with less activity in adult 2. helper T cells - Lymphocyte production declines, and the thymic 3. cytotoxic T cells (Hassall’s) corpuscles become more prominent - Acquire surface receptors for - parenchyma or cellular portion : antigen recognition replaced by loose connective tissue and adipose cells Types: 1. Squamous TECs : form blood-thymus barrier (endothelial cells, epithelial reticular cells and macrophages) which: - Prevent developing lymphocytes from exposure to blood- borne antigens - Macrophages outside of the capillaries prevent blood and cortical T cell interaction which may cause autoimmune attacks 2. Stellate TECs: form cytoreticulum - Endocrine Gland (secretes thymulin, thymopoietin, thymosin, thymic humoral factor,interleukins, and interferon) Fibrous capsule gives off trabeculae (septa) a. APCs w/ MHC I and II :subdivide the gland into incomplete lobules b. Cytokines for T-cell development and other Each lobule consists: immune functions 1. cortex 3. Squamous cortical TECs w/ MHC II dark-staining - Functional Thymic lymphocytes: corticomedullary dense aggregations that do not form barrier between each lymphatic nodules lobule -T lymphoblast, macrophages, thymic epithelial cells (TEC) B. THYMUS MEDULLA 2. medulla Lighter-stained light-staining Few lymphocytes,more epithelial reticular cells only a few lymphocytes but more epithelial Has thymic (Hassall’s) corpuscles: oval reticular cells structures consisting of round or spherical Thymic (Hassall’s) corpuscles are oval aggregations (whorls) of flattened epithelial cells structures consisting of round or spherical which exhibits: calcification or degeneration aggregations (whorls) of flattened epithelial centers that stain pink (eosinophilic) cells. Types of TEC’s: – It exhibit calcification or degeneration centers 1. Second TEC boundary layer between that stain pink or eosinophilic cortex and medulla 2. Cytoreticulum TEC Blood vessels and adipose cells BATCH 2028 1C 9 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. - supports T lymphocytes, dendritic CLINICAL CORRELATION cells, and macrophages. ❖ DiGeorge Syndrome or Thymic Aplasia - expresses specialized proteins Failure of development of 3rd and 4th needed elsewhere in the body pharyngeal pouches : Patient has short 3. Large aggregation of TEC (Hassall’s stature and difficulty in learning corpuscles) activities. - secrete cytokine thymic stromal Absence of the parathyroid glands and lymphopoietin that control local the thymus dendritic activity and factors that Loss of T cell mediated immunity: promote regulatory T cell prone to recurrent fungal and viral development for peripheral tolerance. infection. Mnemonic (CATCH 22) THYMUS T-CELL MATURATION AND SELECTION C- Cardiac abnormalities (Tetralogy After maturation, the T cells leave the thymus of Fallot) gland via the bloodstream and populate the A - Abnormal facies lymph nodes, spleen and other thymus T - Thymic aplasia dependent lymphatic tissues in the organism. C - Cleft palate Two-stage selection process: ensures functional H- Hypocalcemia (due to hypoplasia T cell with receptors (TCR’s) that do not bind of lack parathyroids) major histocompatibility complex (MHC’s) with 22- 22q11 deletion self-antigens Selection process:lasts around 2 weeks where a pre-T lymphocyte begins in the cortex and ends in the medulla ❖ Negative Selection - Occurs in the medulla - Antigen-presenting cells (APC’s) provide T cells with self and foreign antigens - T cells that are unable to recognize foreign antigens or recognize self antigens are eliminated by macrophages (occurs to 95% of the T cells) ❖ Positive Selection - Occurs in the thymic cortex - T lymphocytes that recognize foreign antigens survive, reach maturity, and distributed throughout the lymphatic Thymic Aplasia system - T lymphocytes progeny is established, immunity is maintained without new T cell production - Involutes after puberty , replaced by Soft, loosely organized, highly vascular material adipose tissue, production of T cells separated from osseous tissue by endosteum of decreased. the bone (vertebrae, ribs, sternum, femur, cranium, ends of femur and humerus) As blood cells mature, they push through the reticular and endothelial cells to enter the sinusoids and flow in the blood Responsible for hematopoiesis and source of lymphocytes T lymphocyte Selection BATCH 2028 1C 10 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. Consists of the: gastro-intestinal tract, respiratory tract, gastro urinary tract mucosal lining - Has large diffuse collections of lymphocytes, IgA secreting plasma cells, APC’s, lymphoid nodules One of the largest lymphoid organs containing up to 70% of all the body’s immune cells (B Waldeyer’s ring cells, Helper T cells). Most of the immune cells in MALT are dispersed TYPES OF TONSILS diffusely in the connective tissue; others are found in aggregates that form large, A. Palatine tonsils conspicuous structures such as the tonsils, the Two (2) large ovoid accumulations of Peyer patches in the ileum, and the appendix. lymphoid tissue beneath the mucous membrane; Posteriorly located on the soft palate Stratified squamous nonkeratinized epithelium Large, Irregular masses of lymphoid tissue in the 10-20 deep invaginations or tonsillar crypts mucosa of the posterior oral cavity and in which epithelial lining is densely nasopharynx. infiltrated with lymphocytes and other Late puberty: progressive atrophy leukocytes Blood supply: tonsillar branch of the facial artery - The lymphoid tissue is filled Venous drainage: diffusely with lymphocytes, with - the paratonsillar vein descends from many secondary lymphoid nodules the soft palate across the lateral aspect around the crypts. of the tonsillar capsule Partially encapsulated: (+) dense - nearly always divided in tonsillectomy connective tissue. and may give rise to troublesome - Acts as barrier for spreading hemorrhage tonsillar infection Lymphatic drainage: tonsillar or jugulodigastric node at the angle of the jaw Figure ____ Palatine tonsil B. Lingual tonsil At the base of the tongue Tonsils Surface of the posterior third of the tongue Stratified squamous epithelium with crypts Lack distinct capsules Each tonsil has single crypt; no branching crypts Marker : salivary glands, you are at the base of the tongue and it’s the lingual tonsil. C. Pharyngeal Tonsil An adenoid single medial mass situated in the posterior wall of the nasopharynx Ciliated pseudostratified columnar Tonsillar bed epithelium, and has a thin underlying capsule Form a ring of lymphatic tissue at the entrance - The mucosa with diffuse lymphoid of the oropharynx (aggregations of nodules) tissue and nodules (B cells, T Waldeyer’s ring cells) is invaginated with shallow Reach maximum development in childhood infoldings but lack crypts Involution begins at the age 15 BATCH 2028 1C 11 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. In contact with pathogen: present to T-helper cells Lymphocytes Antibodies in GI are IgA to combat your antigen. Three parts of the tonsils: Palatine, Pharyngeal, & Lingual MEDICAL APPLICATION Tonsillitis - inflammation of the tonsils;more common in children than adults Chronic inflammation of the pharyngeal lymphoid tissue and tonsils of children often produces hyperplasia and enlargement of the tonsils to form “adenoids”, which can obstruct A section through a Peyer patch shows a few lymphoid the eustachian tube and lead to middle ear nodules infections. Tonsillectomy - procedure of removal of the tonsils. Five times occurrence of tonsillitis in a year would likely be a candidate for tonsillectomy. First line treatment : Antibiotics Summary diagram showing antigens in the gut lumen A blind evagination of the cecum, the appendix is a significant part of the MALT with its lamina propria and submucosa filled with lymphocytes and lymphoid follicles. Tonsillitis (top) and adenoids (bottom) Aggregations of lymphatic nodules (T and B lymphocytes) in the wall of the ileum which allow close monitoring of the microorganisms in the gut Located in the distal ileum Present in the GI tract: Antigen-presenting cells BATCH 2028 1C 12 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. LM of the mucosa of the appendix showing gut-associated lymphoid tissue. Diffuse infiltration of lymphocytes characterizes the lamina propria (LP) just under the epithelium (Ep). Lymphocytes usually migrate from the lamina propria and cross the epithelium on their All the formed elements of blood must reenter way to the lumen. Small round nuclei of these the vasculature by passing through narrow slits lymphocytes (arrows) are seen in the epithelium. between the stave cells into the sinusoids. 250x. HIE 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 Largest lymphatic organ (75-300 gms) Encapsulated with fibrous capsule Filters blood and reacts immunologically to blood-borne antigens Graveyard of RBC (120 days) Hematopoiesis in fetal life ~ 5 months Splenic ligaments (avascular) except the gastrosplenic ligaments (short gastric artery)) White Pulp Although the spleen performs various important functions in the body, it is not an essential organ for life. 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. BATCH 2028 1C 13 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. Immune component of the spleen: Medical applications: Lymphatic tissue Postsplenectomy : OPSI Lymphatic cells that surround the central arteries ○ Susceptible: encapsulated organisms, of the white pulp are primarily T cells especially H. influenzae, S. Lymphatic nodules mainly B cells pneumoniae, and meningococci. APC’s and macrophages ○ Properdin helps initiate the alternative detect trapped bacteria and antigens and initiate pathway of complement activation, immune responses against them. which is particularly useful for fighting Macrophages in the spleen also break down encapsulated organisms. hemoglobin of worn-out erythrocytes ○ Tuftsin enhances the phagocytic activity of PMNs and macrophages Red Pulp After surgical removal of the spleen (splenectomy), 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. 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 Lymphatic System – Integral part of the immune and cells in the splenic cords circulatory system In 1627- Gasparo Aselli ~ “lymphatic system Functions: “Hippocrates reported “white blood” in nodes Blood filtration in the open circulation involves Aristotle described fibers containing colorless interaction with splenic cord macrophages that fluid observed between blood vessels and remove old, swollen RBCs unable to slip nerves. (LYMPH) between stave cells to reenter the venous blood Science of lymphology : Lymphatic vascular biology flow Early investigations of the anatomy and graveyard of RBCs and recycling of iron for physiology of the lymphatic system, its function, erythropoiesIs and implications related to cancer have After surgical removal of the spleen propelled technology and research to elucidate (splenectomy), the number of abnormal many of the enigmatic characteristics of the erythrocytes in the circulation increases lymphatic system. although most such cells are then removed by Recent research has implicated the lymphatic macrophages in sinusoids of the bone marrow system in the pathogenesis of cardiovascular and liver. diseases including obesity and metabolic disease, dyslipidemia, inflammation, Trauma: relatively thin capsule atherosclerosis, hypertension, and myocardial Splenomegaly: Lymphoma or other malignant growth, infarction. infections such as mononucleosis, or sickle cell disease and other types of anemia. BATCH 2028 1C 14 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. Lymphatic System Development: parallels that of blood structures General Functions of Lymphatic System: Primordial LS : 6th wks in the form of lymph sacs 1. Returns Fluid from Tissues to Blood (2-4 liters 8th wks: cisterna chyli of interstitial fluid /day) (prevention & resolution Communicating channels connecting the lymph of edema) sacs (thoracic duct : 9th wk) 2. Returns Large Molecules to Blood (maintenance of interstitial fluid homeostasis) 3. Absorb and Transport Fats 4. Hemopoiesis 5. Body Defense/Immunity Components of the Lymphatic system: 1. Circulating lymphocytes 2. Lymph vessels 3. Central (primary) lymphoid organs: bone marrow and thymus 4. Peripheral (secondary) lymphoid organs: lymph nodes. spleen, tonsils, mucosa associated lymphoid tissues - The lymphatic vessels are found in almost every vascularized tissue except neural tissue and bone marrow. A. Unidirectional lymphatic vascular system consists: ○ lymphatic capillaries ○ collecting lymphatic vessels ○ lymph nodes, ○ thoracic duct and right lymphatic trunk BATCH 2028 1C 15 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. B. LYMPHATIC CAPILLARIES Lymphatic capillaries absorb interstitial solutes, macromolecules, and immune cells that extravasate from the blood vascular system. Lymph formation is facilitated by the discontinuous basement membrane (red dashed line), and button-like endothelial junctions allow passive paracellular flow for lymph formation. Structural features: ○ Lumen-filled with eosinophilic material (NO RBC) ○ partial basement membrane and not ensheathed by smooth muscles ○ anchoring filaments tethering the interstitial matrix to interstitial fluid ○ Single layer of endothelium that are interconnected by discontinuous junctional structures known as buttons Buttons - Very small tight junctions between endothelial cells 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 VESSELS General Plan of Drainage of Lymph continuous junctional structures (zipper-like junctions lymphatic valves) contractile smooth muscle cells (SMCs) : pumping force for lymph movement unidirectional propulsion of lymph FACTORS THAT HELP IN LYMPH FLOW: Tissue fluid pressure Contraction of surrounding muscle (exercise,massage,pneumatic compression) Breathing movements (negative intrathoracic pressure) Rhythmic contraction of smooth muscle walls in vessels wall (pulsations of adjacent arteries) 5. Presence of valves which prevent backflow BATCH 2028 1C 16 HISTOLOGY LC 3: immune System and Lymphoid Organs DR. REFUERZO, V. D. LYMPH NODE - Organization of the lymph node with afferent lymphatic vessels and a single efferent lymphatic vessel Functions: - To protect organisms (body) from INVASION and DAMAGE by microorganisms (bacteria, virus) and foreign substances (antigen, protein E. LYMPHOVENOUS VALVES molecules etc..) - Lymph drains into venous circulation through 4 distinct lymphovenous valves located where the Components of the immune system internal jugular vein (IJV) and external jugular Lymphoid organs vein (EJV) drain into the subclavian vein (SCV) ○ spleen ○ lymph nodes ○ tonsils ○ thymus ○ bone marrow Lymphoid nodules ○ A network of reticular fibers and spherical,non-encapsulated aggregations of lymphocytes Free cells ○ lymphocytes, granulocytes, mononuclear phagocytes present in blood, lymph and connective tissue Antigen presenting cells ○ In various tissues of the body heavily exposed to antigen (langerhans cell in epidermis) Junqueira’s Basic Histology, 15th edition BATCH 2028 1C 17