Histology Lymphoid Organs PDF

HISTOLOGY | LYMPHOID ORGANS II. INNATE AND ADAPTIVE IMMUNITY USLS COLLEGE OF MEDICINE  INNATE IMMUNITY...

HISTOLOGY | LYMPHOID ORGANS II. INNATE AND ADAPTIVE IMMUNITY USLS COLLEGE OF MEDICINE  INNATE IMMUNITY HISTOLOGY – Immediate, nonspecific actions – Include physical barriers such as the skin and mucous TITLE: LYMPHOID ORGANS membranes of the gastrointestinal, respiratory, and DATE: 10/19/20 urogenital tracts LECTURER: Dr. Pedroza ◌ Neutrophils and other leukocytes remove Bacteria, fungi, and parasites that manage to penetrate the barriers ◌ Toll-like receptors (TLRs) on leukocytes allow the recognition OUTLINE and binding of surface components of such invaders. I. INTRODUCTION ◌ Natural killer (NK) cells destroy unhealthy host cells, including II. INNATE AND ADAPTIVE IMMUNITY those infected with virus or bacteria, and tumorigenic cells. III. CYTOKINES ◌ Antimicrobial chemicals produced by leukocytes and IV. ANTIGENS & ANTIBODIES specific cells of the tissue barriers A.Classes of Antibodies Hydrochloric acid (HCl) and organic acids B.Actions of Antibodies – lower the pH locally to either kill entering V. ANTIGEN PRESENTATION microorganisms directly or inhibit their growth. VI. CELLS OF ADAPTIVE IMMUNITY A.Antigen-Presenting Cells Defensins B.Lymphocytes – short cationic polypeptides produced by 1. T-cells neutrophils and various epithelial cells that kill 2. B-cells bacteria by disrupting the cell walls. VII. THYMUS Lysozyme A.Role of the Thymus in T-Cell Maturation & Selection – an enzyme made by neutrophils and cells of VIII. MUCOSA-ASSOCIATED LYMPHOID TISSUE epithelial barriers A.Tonsils – hydrolyzes bacterial cell wall components, killing 1. Palatine those cells. 2.Lingual Complement 3.Pharyngeal – a system of proteins that react with bacterial B. Peyers patches surface components to aid removal of bacteria. C. M Cells Interferons D. Appendix – paracrine factors from leukocytes and IX. LYMPH NODES virus-infected cells X. SPLEEN – signal NK cells to kill such cells and adjacent cells to A.Functions of splenic white & red pulp resist viral infection B.Blood flow XI. SUMMARY OF KEY POINTS  ADAPTIVE IMMUNITY – Acquired gradually by exposure to microorganisms – More specific, slower to respond – Evolutionarily more recent development than innate immunity. I. INTRODUCTION – involves B and T lymphocytes which become activated  IMMUNE SYSTEM against specific invaders by being presented with specific – Provides defense or immunity against infectious agents molecules from those cells by Antigen Presenting Cells – Consists of leukocytes located within every tissue of the (APCs), which are usually derived from monocytes. body and lymphoid organs – aimed at specific microbial invaders – Interconnected only by the blood and lymphatic – involve production of memory lymphocytes so that a circulation similar response can be mounted very rapidly if that  PRIMARY LYMPHOID ORGANS invader ever appears again. – Where lymphocytes are initially formed the ◌ Thymus ◌ Bone marrow  SECONDARY LYMPHOID ORGANS – Where lymphocyte activation and proliferation occur ◌ Lymph nodes ◌ Spleen ◌ Peyer patches ◌ Appendix  MUCOSA-ASSOCIATED LYMPHOID TISSUE(MALT) ◌ Comprised of immune cells located diffusely in the digestive, respiratory, or urogenital mucosae. ◌ Proliferating B lymphocytes in the secondary structures of MALT are arranged in small spherical lymphoid nodules. Transcribers: Dalipe, Lagansoa 1 Reference: Junqueira’s Basic Histology HISTOLOGY | LYMPHOID ORGANS Transcribers: Dalipe, Lagansoa 2 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS III. CYTOKINES ◌ Immune response to antigens may be:  Used by lymphoid tissues in communication with each other to coordinate defensive measures. Cellular – in which lymphocytes are primarily in charge of eliminating the antigen  Coordinate cell activities in the innate and adaptive immune responses. Humoral – in which antibodies are primarily responsible for the response  Involved in both innate and adaptive immunity or Both  Diverse group of peptides and glycoproteins, usually with low molecular masses (between 8 and 80 kDa)  ANTIBODY  Paracrine mode of action. – Glycoprotein of the immunoglobulin family  FUNCTIONS – Interacts specifically with an antigenic determinant (epitope) ◌ Directed cell movements, or chemotaxis, toward and cell accumulation at sites of inflammation, for example, during – Secreted by plasma cells (terminally differentiated B diapedesis. lymphocytes) whose receptors recognize and bind specific epitopes – Cytokines producing this effect are also called chemokines. ◌ Can be found in: ◌ Increased mitotic activity in certain leukocytes Blood plasma and interstitial fluid of tissues ◌ Stimulation or suppression of lymphocyte activities in Transported across epithelia into the secretion of adaptive immunity. Named interleukins because they were glands such as mucous, salivary, and mammary thought to be produced by and to target only leukocytes. glands. ◌ Stimulated phagocytosis or directed cell killing by innate Membrane proteins on the surface of B lymphocytes or other leukocytes immune cells. ◌ Immunoglobulins of all antibody molecules have a common  Have multiple target cells in which they exert several effects design:  Some are produced by and target cells besides immune cells. – two identical light chains and two identical heavy chains bound by disulfide bonds Fc region: – the constant, isolated carboxyl-terminal portion of the heavy-chain molecules – recognized by cell surface receptors on basophils and mast cells, localizing these antibodies to the surface of these cells Variable region: – first 110 amino acids near the amino-terminal ends of the light and heavy chains vary widely among different antibody molecules Antigen-binding site: – made of variable portions of one heavy and one light chain – DNA sequences coding for these regions undergo recombination and rearrangement after B lymphocytes are activated against a specific antigen and the progeny of those cells all produce antibodies that specifically bind that antigen. – Each antibody has two antigen-binding sites, both for the same antigen. IV. ANTIGENS & ANTIBODIES  ANTIGEN – Molecule that is recognized by cells of the adaptive immune system – Elicits a response from these cells – consist of soluble molecules (such as proteins or polysaccharides) or molecules that are components of intact cells ◌ EPITOPES – known as antigenic determinants – small molecular domains of the antigen recognized by immune cells Transcribers: Dalipe, Lagansoa 3 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS  IgD – Least abundant immunoglobulin in plasma – Least understood class of antibody – Monomers of IgD are bound to the surface of B lymphocytes where they (along with IgM monomers) act as antigen receptors in triggering B-cell activation. B. Actions of Antibodies  ANTIGEN-BINDING SITES of IgG and IgA – Bind specifically and neutralize certain viral particles and bacterial toxins – Agglutinate many bacterial cells – Precipitate most soluble antigens  FC PORTIONS all antibodies – Bind to receptors and optimize three important actions of innate immunity ◌ Complement activation – IgG or IgM bind polypeptides of the complement system and activate them through a cascade of enzymatic reactions. Complement system – a group of around 20 plasma proteins produced mainly in the liver – After activation, specific complement components A.Classes of Antibodies bind and rupture membranes of invading cells, clump – Five major classes antigen bearing bacteria or cells, and elicit arrival of  IgG relevant leukocytes. – Most abundant class representing 75%-85% of the ◌ Opsonization immunoglobulin in blood. – Ability of receptors on macrophages, neutrophils, and – Production increases during immune responses following eosinophils to recognize and bind the Fc portions of infections, etc. antibodies attached to surface antigens of – Highly soluble, stable (half-life > 3 weeks) microorganisms – Crosses the placental barrier into the fetal circulation. This – Greatly increases the efficiency of phagocytosis by confers passive immunity against certain infections until the these leukocytes at sites of infection. newborn’s own adaptive immune system is acquired. ◌ NK cells activation  IgA – Antibodies bound to antigens on virus-infected cells of – Present in almost all exocrine secretions as a dimeric form in the body are recognized by the primitive lymphocytes which the heavy chains of two monomers are united by a called NK cells polypeptide called the J chain – Activated NK cells kill the infected cell by releasing – Produced by plasma cells in mucosae of the digestive, perforin and various granzymes. These two proteins respiratory, and reproductive tracts. together enter the infected cell via other receptors – Secretory component: protein released by the epithelial cells and cause apoptosis as IgA undergoes transcytosis. Attaches to IgA. The resulting structure is relatively resistant to proteolysis and reacts with microorganisms in milk, saliva, tears, and mucus coating the V. ANTIGEN PRESENTATION mucosae in which it is made.  MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)  IgM – Antigens recognized by lymphocytes bound to specialized – 5%-10% of blood immunoglobulin and usually exits in a integral membrane protein complexes on cells surfaces pentameric form united by a J chain. – Two key types called MHC class I and class II. – Produced in an initial response to an antigen. – First recognized by their roles in the immune rejection of – If bound to antigen, is the most effective antibody class in grafted tissue or organs activating the complement system – On human cells, are often called human leukocyte  IgE antigens (HLAs), are encoded by genes in large – Monomer chromosomal loci having very high degrees of allelic – Much less abundant in the circulation variation between different individuals – Exists bound at its Fc region to receptors on the surface of – T lymphocytes are specialized to recognize both classes of mast cells and basophils. MHC proteins and the antigens they present. – When it encounters the antigen that elicited its production, – If MHCs on cells of a tissue graft are not similar to those the antigen-antibody complex triggers the production of that T lymphocytes encountered during their biologically active substances, such as histamine, heparin, development, the grafted cells will induce a strong and leukotrienes. This characterizes an allergic reaction, immune reaction by T cells of the recipient. which is thus mediated by the binding of cell-bound IgE with – Unfamiliar MHC epitopes on the graft’s cells are the antigens (allergens) that stimulated the IgE to be recognized as markers of potentially tumorigenic, synthesized initially infected, or otherwise abnormal (“non-self ”) cells that they must eliminate. – Made in the rough ER and Golgi apparatus Transcribers: Dalipe, Lagansoa 4 Reference: Junqueira’s Basic Histology HISTOLOGY | LYMPHOID ORGANS Transcribers: Dalipe, Lagansoa 5 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS ◌ MHC class I proteins A. Antigen-Presenting Cells – Bind a wide variety of proteasome-derived peptide  Part of the mononuclear phagocyte system fragments representing the range of all proteins  Includes all types of macrophages and specialized dendritic synthesized in that cell. cells – Present on the surface of all nucleated cells  Features common to all APCs – “Self-antigens” – recognized by T cells as a signal to – Active endocytotic system ignore those cells – Expression of MHC class II molecules for presenting – Virally infected cells or cells with proteins altered by peptides of exogenous antigens gene mutation also have MHC class I proteins  “professional” APCs also include thymic epithelial cells displaying peptides that T cells do not recognize as  During inflammation transient expression of MHC “self,” helping lead to the elimination of such cells. class II is induced by interferon-γ in certain local cells that can ◌ MHC class II proteins be considered “nonprofessional” APCs, including fibroblasts – Synthesized and transported to the cell surface but and vascular endothelial cells. only in cells of the mononuclear phagocyte system and certain other cells – Before joining the plasmalemma,Golgi-derived vesicles B. Lymphocytes with the MHC class II complexes first fuse with  Regulate and carry out adaptive immunity endolysosomal vesicles containing antigens ingested  In adults stem cells for all lymphocytes are located in the red by receptor mediated endocytosis, pinocytosis, or bone marrow phagocytosis. This allows the class II proteins to bind  Cells of the major lymphoid lineages mature and become fragments of whatever proteins the cells had ingested, functional in two central or Primary lymphoid organs. including those from dead, infected, or abnormal cells ◌ Cells destined to become B lymphocytes remain and and atypical proteins of all kinds. differentiate further in the bone marrow. – At the surface of these cells, the class II complexes ◌ Progenitors of T lymphocytes move via the circulation into display the peptides from these potentially the developing thymus. pathogenic cells, signaling T lymphocytes and activating their responses against sources of these  After maturation in these primary structures, B and T cells circulate to the peripheral secondary lymphoid organs antigens. ◌ MALT ◌ Lymph nodes VI. CELLS OF ADAPTIVE IMMUNITY ◌ Spleen  Lymphocytes and the monocyte-derived cells specialized for  Lymphocytes do not stay long in the lymphoid organs; they antigen presentation to lymphocytes are the major players in continuously recirculate through the body in connective tissues, adaptive immune responses. blood, and lymph.  Lymphoid tissue – Reticular connective tissue filled with large numbers of lymphocytes – Also contains various APCs and plasma cells. – Can be either diffuse within areas of loose connective tissue or surrounded by capsules, forming discrete (secondary) lymphoid organs. – Because lymphocytes have prominent basophilic nuclei and very little cytoplasm, lymphoid tissue packed with such cells usually stains dark blue in hematoxylin and eosin (H&E)– stained sections. – In secondary lymphoid tissue, the lymphocytes are supported by a rich reticulin fiber network of type III collagen produced by fibroblastic reticular cells  Most lymphocytes are morphologically indistinguishable in either the light or electron microscope  Various surface proteins (“cluster of differentiation” or CD markers) allow them to be distinguished as B cells and subcategories of T cells by immunocytochemical methods.  Key features of B and T lymphocytes also include the surface receptors involved in activating their different responses to antigens ◌ Receptors of B cells are immunoglobulins that bind antigens directly ◌ T cells react only with antigen on MHC molecules and this requires the additional cell surface proteins CD4 or CD8. Transcribers: Dalipe, Lagansoa 6 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS  Lymphocytes in the marrow and thymus of a newborn infant not yet exposed to antigens are immunocompetent but naive and unable to recognize antigens  After circulating to the various secondary lymphoid structures, lymphocytes are exposed to antigens on APCs and become activated, proliferating to produce a clone of lymphocytes all able to recognize that antigen. Transcribers: Dalipe, Lagansoa 7 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS 1. T - Cells  Long-lived lymphocytes  Constitute nearly 75% of the circulating lymphocytes  Recognize antigenic epitopes via surface protein complexes termed T-cell receptors (TCRs). – Made of two glycoproteins called the α and β chains, each with variable regions produced similarly to those of immunoglobulins – TCRs only recognize antigenic peptides when presented as part of MHC molecules (interacting with both the MHC and the peptide it presents), T lymphocytes are said to be MHC restricted. 2. B - Cells  Several types of T lymphocytes exist, with various functions: ◌ Helper T cells (Th cells)  Surface receptors for antigens are monomers of IgM or IgD, – Characterized by CD4, the coreceptor with the TCR with each B cell covered by B-cell receptors (BCRs). for binding MHC class II molecules and the – Bind an antigen, which may be free in solution, on an peptides they are presenting. exposed part of an infectious agent, or already bound – Assist immune responses by producing cytokines to antibodies, and the surface complexes then undergo that promote differentiation of B cells into plasma endocytosis. cells, activate macrophages to become – Degraded in endosomes, peptides from the antigens phagocytic, activate cytotoxic T lymphocytes are presented on MHC class II molecules of the B cell. (CTLs), and induce many parts of an inflammatory – A helper T cell then binds this B cell and activates it reaction. further with a cytokine, inducing recombination in the – Some specifically activated helper T cells persist as immunoglobulin genes and stimulating several cycles long-lived memory helper T cells, which allow a of cell proliferation more rapid response if the antigen appears again  Provide humoral immunity. later.  In all secondary lymphoid tissues B lymphocytes interact ◌ CTL with scattered follicular dendritic cells (FDCs) – CD8+ – Have long filamentous processes. – Their TCRs, together with CD8 coreceptors bind – Mesenchymal in origin and their function does not specific antigens on foreign cells or virusinfected involve MHC class II molecules. cells displayed by MHC class I molecules.  Surfaces of these cells are covered with antibody-antigen – In the presence of interleukin-2 (IL-2) from helper complexes bound to receptors for complement proteins and T cells, cytotoxic T cells that have recognized such for immunoglobulin Fc regions, causing B cells to attach, antigens are activated and proliferate. become activated, and aggregate as a small primary – Also called killer T cells, they attach to the cell lymphoid nodule (or follicle) sources of the antigens and remove them by  With the help of adjacent T cells, these B cells now form a releasing perforins and granzymes, which trigger much larger and more prominent secondary lymphoid apoptosis. This represents cell-mediated immunity nodule and its mechanism is largely similar to that of NK  Secondary nodules cells. – Characterized by a lightly stained germinal center filled – Activation of cytotoxic T cells also results in a with large lymphoblasts (or centroblasts) undergoing population of memory cytotoxic T cells. immunoglobulin gene recombination, rapid ◌ Regulatory T cells (Tregs or suppressor T cells) proliferation, and quality control. – CD4+ CD25+ – Growth of activated B cells in germinal centers is – Serve to inhibit specific immune responses. exuberate and very rapid, causing naive, – Identified by the presence of the Foxp3 nonproliferating B cells to be pushed aside and transcription factor, play crucial roles in allowing produce the more darkly stained peripheral mantle immune tolerance, maintaining unresponsiveness  After 2 to 3 weeks of proliferation, most cells of the germinal to self-antigens and suppressing excessive  center and mantle are dispersed and the structure of the immune responses. secondary lymphoid nodule is gradually lost. – Produce peripheral tolerance, which acts to  Most of these new, specific B lymphocytes differentiate into supplement the central tolerance that develops in plasma cells secreting antibodies that will bind the same the thymus. epitope recognized by the activated B cell. ◌ γδ T lymphocytes  Newly formed B cells remain as long-lived memory B cells – Smaller subpopulation whose TCRs contain γ which is a key feature of adaptive immunity, which allows a (gamma) and δ (delta) chains instead of α very rapid response upon subsequent exposure to the same antigen. and β chains. – The γδ T cells migrate to the epidermis and mucosal epithelia, becoming largely intraepithelial, and do not recirculate to secondary lymphoid organs. – They function in many ways like cells of innate immunity, in the front lines against invading microorganisms. Transcribers: Dalipe, Lagansoa 8 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS VII. THYMUS ◌ Stellate TECs  A bilobed structure in the mediastinum where T cells are – Have processes containing keratin tonofilaments joined produced by desmosomes, form a cytoreticulum to which  Main function is induction of central tolerance, which along macrophages and developing lymphocytes attach with regulatory T cells prevents autoimmunity instead of to reticulin fibers.  Originates from the embryo’s third pair of pharyngeal – Are APCs, expressing MHC class II molecules in addition pouches (endoderm), with precursor lymphoblasts from the to MHC class I. bone marrow to invade and proliferate in the thymic – Secrete numerous cytokines for T-cell development and epithelium during its development. other immune function  Fully formed and functional at birth,the thymus remains ◌ Other squamous cortical TECs large and very active in T-cell production until puberty – Also express MHC class II molecules but form a sheetlike during which it normally undergoes involution structure contributing to a functional corticomedullary  Has a vascularized connective tissue capsule that extends barrier between these two regions of each lobule. septa into the parenchyma, dividing the organ into many  The more lightly stained thymic medulla contains fewer and incompletely separated lobules larger, more mature lymphocytes. – Each lobule has an outer darkly basophilic cortex  3 types of TEC in the MEDULLA surrounding a more lightly stained medulla. ◌ A second layer of the boundary between cortex and – Staining differences reflect the much greater density medulla. of lymphoblasts and small lymphocytes in the cortex ◌ A cytoreticulum that (1) supports T lymphocytes, dendritic than the medulla cells, and macrophages (all less densely packed than in the  Thymic cortex contains an extensive population of T cortex), and (2) expresses many specialized proteins lymphoblasts (or thymocytes), located among numerous specific to cells of other organs. macrophages and associated with the unique thymic ◌ Large aggregates of TECs, sometimes concentrically epithelial cells (TECs) that have certain features of both arranged, called Hassall corpuscles. epithelial and reticular cells. – Up to 100 μm in diameter  3 types of TEC in the CORTEX – Thymic corpuscles are unique to the medulla ◌ Squamous TEC – Secrete several cytokines that control activity of local – Forms a layer joined by desmosomes and occluding dendritic cells, including factors that promote junctions and line the connective tissue of the capsule development of regulatory T cells for peripheral and septa and surround the microvasculature creating tolerance. an isolated cortical compartment and, together with  The microvasculature of the medulla: the vascular endothelial cells and pericytes, forms a – Not surrounded by a tight layer of TECs blood-thymus barrier preventing unregulated – Mature T lymphocytes exit through the walls of venules and exposure of thymocytes to antigens. efferent lymphatics Transcribers: Dalipe, Lagansoa 9 Reference: Junqueira’s Basic Histology HISTOLOGY | LYMPHOID ORGANS Transcribers: Dalipe, Lagansoa 10 Reference: Junqueira’s Basic Histology HISTOLOGY | LYMPHOID ORGANS Transcribers: Dalipe, Lagansoa 11 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS A.Role of the Thymus in T-Cell Maturation & Selection  Thymus – site of T-lymphocyte differentiation and the selective removal of T cells reactive against self-antigens, a key part of inducing central self-tolerance.  T lymphoblasts – Do not yet express CD4, CD8, or a TCR – Will populate the cortex and begin to proliferate, recombine variable regions of the TCR α and β chain genes, and then express these TCR proteins as well as both CD4 and CD8. – With these key functional components in place, 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 not recognize and strongly bind MHC with self-antigens.  SELECTION PROCESS ◌ Begins in the cortex, ends in the medulla, and lasts about 2 weeks. ◌ TECs in the cytoreticulum of the cortex present the developing thymocytes with peptides on both MHC class I and class II proteins, which are important for development of CD8+ and CD4+ T cells. ◌ Cells are examined by positive selection, with a cell’s survival depending on whether its TCRs can recognize and bind antigens on the MHC molecules properly. If the cell cannot pass this test, they undergo apoptosis and are removed by the macrophages. Cells then move to the medulla. ◌ In the medulla T cells with functional TCRs encounter antigens presented on both cytoreticular TECs and dendritic cells. Here the focus is on removing T cells whose TCRs strongly bind self-antigens, a process called negative selection because survival depends on a cell not binding to MHC molecules with such peptides. This occurs because medullary thymic epithelial cells express high levels of the gene Aire (autoimmune regulator), which are transferred to dendritic cells for presentation to T cells. T cells that react undergo apoptosis. ◌ Depending on which class of MHC they interacted with, most of these lymphocytes will have stopped expressing either CD8 or CD4, and become either helper T cells or cytotoxic T cells  Deletion of self-reactive helper and cytotoxic T lymphocytes in the thymus is the basis for the central immunotolerance.  Supplementing this throughout the body is the peripheral tolerance mediated by regulatory T cells, which also develop initially in the thymic medulla under the influence of cytokines from Hassall corpuscles. Transcribers: Dalipe, Lagansoa 12 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS VIII. MUCOSA-ASSOCIATED LYMPHOID TISSUE  Secondary lymphoid structures – where most lymphocytes are 2. Lingual activated by antigen presentation – Mucosa associated lymphoid tissue, lymph nodes &  At the base of the tongue spleen  Covered by stratified squamous epithelium with crypts  Mucosa/inner lining of the digestive, respiratory &  Have fenestrae but lack distinct capsules genitourinary – common site of invasion by pathogens because their lumens open to the external environment 3. Pharyngeal ◌ To protect it against invaders:  In the posterior wall of the nasopharynx – Diffuse collection of lymphocytes  Covered by pseudostratified ciliated columnar epithelium – IgA secreting plasma cells  Has thin underlying capsule – 3APCs  The mucosa with diffuse lymphoid tissue and lymphoid nodules – Lymphoid nodules is invaginated with swallowing infoldings but lacks crypts – Lymphocytes  Immune cells in MALT are found in aggregates that form large, conspicuous structures such as: – TONSILS – PEYER PATCHES in the Ileum – APPENDIX  MALT – One of the largest lymphoid organ – Contains 70% of the body’s immune cells – Most of the lymphocytes are B CELLS – Among the T CELLS, CD4+ Helper T cells predominate A.Tonsils  Large, irregular masses of lymphoid tissue 1. Palatine  Located posteriorly on the soft palate; covered by stratified squamous epithelium  The surface area is enlarged with 10-20 deep invaginations or TONSILLAR CRYPTS in which the epithelial lining is densely infiltrated with lymphocytes and other leukocytes.  Filled diffusely with lymphocytes, secondary lymph nodules around the crypts  Underlain by DENSE CONNECTIVE TISSUE that acts as a partial capsule Transcribers: Dalipe, Lagansoa 13 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS B. Peyers patches  Large aggregates of the lymphoid nodules  Each contains a dozen of nodules with no underlying connective tissue capsule D. Appendix  Short, small diameter projection from the cecum  The mucosa is almost filled with lymphoid tissue, effacing the glands C. M cells  Simple columnar epithelium that covers the lymphoid nodules of Peyer patches Transcribers: Dalipe, Lagansoa 14 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS IX. LYMPH NODES  Bean shaped, encapsulated structures about 10 mm by 2.5cm in size  A total of 400-450 lymph nodes are present, most abundantly in the axillae (armpits) and groin, along the major vessels of the neck & in the thorax and abdomen especially ion mesenteries.  Embedded in the loose connective tissue, a lymph node has a convex surface where afferent lymphatics enter and a concave depression, the hilum, where an efferent lymphatic leaves and where an artery, vein and nerve penetrate the organ.  Dense connective tissue capsule surrounds the lymph node  Most abundant cells of the lymph nodes are the lymphocytes of all types, plasma cells, dendritic cells, macrophages & other APCs  The cells are arranged in a stroma of reticulin fibers & reticular cells to form three major regions: ◌ An outer CORTEX SUBCUPSULAR SINUS – immediately inside the capsule – Receives lymph from the afferent lymphatics – Cortical sinuses branch internally among the lymphoid nodules along trabeculae – Lined by discontinuous endothelium penetrated by reticulin fibers & processes of dendritic cells LYMHPOID NODULES – w/ or w/o germinal centers – Fill most cortical areas – Formed largely by helper T lymphocytes and proliferating B lymphoblasts – Each nodule is organized around the long, interdigitating processes of follicular dendritic cells (FDCs) – Not routinely seen by light microscopy ◌ CENTRAL MEDULLA – has 2 major components: MEDULLARY CORDS – branched cordlike masses of lymphoid tissue extending from the paracortex – Contain T&B lymphocytes and many plasma cells MEDULLARY SINUS – dilates spaces lined by discontinuous endothelium that separate the medullary cords. – Its lumen includes a meshwork of processes form reticular cells which represent a final lymph filter. – Contain many macrophages and sometimes neutrophils if the lymph node is draining an infected region – Are continuous with the cortical sinuses and converge at the hilum as the efferent lymphatic vessel ◌ PARACORTEX – area between the 2 – Can be distinguished from the outer cortex by its lack of B cell lymphoid nodules – Contains lymphoid tissue rich T cells that can be seen by immunohistochemistry. HIGH ENDOTHELIAL VENULES – specialized postcapillary venules – Important entry point for most lymphocytes in the lymph nodes – Endothelial lining of cuboidal cells whose apical surface glycoproteins and integrins facilitate rapid diapedesis of lymphocytes out of the blood into the para cortex of the lymph node Transcribers: Dalipe, Lagansoa 15 Reference: Junqueira’s Basic Histology HISTOLOGY | LYMPHOID ORGANS X. SPLEEN  Contains the largest single accumulation of lymphoid tissue in the body  The only lymphoid organ involved in filtration of blood, making it an important organ in defense against blood-borne antigens.  Main site of old RBCs destruction  Production site of antibodies & activated lymphocytes  Located in the UQ of the abdomen  Surrounded by a capsule of dense connective tissue from which emerge trabeculae to penetrate the parenchyma or splenic pulp A. Functions of splenic white & red pulp  WHITE Pulp – 20% of the spleen – Consist of lymphoid nodules and periarteriolar lymphoid sheaths (PALS)  RED Pulp – consist of blood-filled sinusoids and splenic cords. – Removal of defective RBCs  Branching from the hilum, small trabecular arteries leave the trabecular connective tissue and enter the parenchyma as arterioles enveloped by the PALS, which consist primarily of T cells with some macrophages, DCs and plasma cells as part of the white pulp. Surrounded by the PALS, they are known as CENTRAL ARTERIOLES.  Each central arteriole leaves the white pulp and enters the red pulp, losing its sheath of lymphocytes & branching as PENICILLAR ARTERIOLES that continue as capillaries.  The red pulp is composed almost entirely of splenic cords (of Billroth) and splenic sinusoids; and is the site where effete RBCs in blood are removed.  STAVE CELLS – unusual endothelial cells that line the sinusoids; oriented parallel to the blood flow and sparsely wrapped in reticular fibers & highly discontinuous basal lamina Transcribers: Dalipe, Lagansoa 16 Reference: Junqueira’s Basic Histology HISTOLOGY | LYMPHOID ORGANS B. Blood flow  CLOSED CIRCULATION – capillaries branching from the penicillar arterioles connect directly to the sinusoids and the blood is always enclosed by endothelium  OPEN CIRCULATION – capillaries from about half of the penicillar arterioles are uniquely open ended, dumping blood into the stroma of the splenic cords. – Plasma and all the formed elements of blood must reenter the vasculature by passing through narrow slits between the stave cells into the sinusoids. Transcribers: Dalipe, Lagansoa 17 Reference: Junqueira’s Basic Histology HISTOLOGY | LYMPHOID ORGANS Transcribers: Dalipe, Lagansoa 18 Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS XI. SUMMARY OF KEY POINTS Thymus Basic immunology  T lymphoblasts, or thymocytes, attach in the thymus to a cytoreticulum composed of interconnected thymic epithelial  Innate immunity is present from birth and involves leukocytes cells (TECs). (mainly granulocytes), and proteins such as defensins, complement, lysozyme, and interferons; adaptive immunity  The thymic epithelial cells (TECs) also secrete many develops more slowly and is based on antigen presentation to cytokines, compartmentalize the thymus into a cortex and a lymphocytes. medulla, and in the cortex surround blood vessels in the blood-thymus barrier.  Immune cells communicate with one another and regulate one another’s activities via polypeptide hormones called cytokines.  Developing T cells with nonfunctional TCRs are detected and removed in the thymic cortex by a process of positive  Antigens are the regions of macromolecules, usually proteins, selection; cells with functional TCRs move into the thymic that are recognized by lymphocytes to elicit a specific immune medulla. response against them.  In the thymic medulla T cells whose TCRs bind strongly to  Antibodies are immunoglobulins produced by plasma cells after “selfproteins,” including proteins of many nonthymus cell a progenitor B cell is activated by a specific antigen and types made by thymic epithelial cells expressing the Aire rearranges its immunoglobulin genes so the antibody matches gene, are induced to undergo apoptosis there in a process of the antigen. negative selection.  Surfaces of all nucleated cells bear fragments of their  This two-stage thymic selection leads to central immune constituent proteins on major histocompatibility complex tolerance, producing functional T cells that do not bind to (MHC) class I molecules. proteins of the host.  Only antigen-presenting cells (APCs), mostly derived from  Peripheral immune tolerance occurs throughout the body monocytes, also present fragments of endocytosed foreign when specific immune reactions are suppressed by (usually from microorganisms) proteins on surface MHC class II regulatory T cells that also originate largely in the thymic molecules. medulla.  Regulatory T cells form in the thymus upon interacting with Lymphocyte Origins and Differentiation dendritic cells presenting self-antigens in a process promoted  Lymphocytes originate in the primary lymphoid organs: bone by cytokines from thymic epithelial cell (TEC) aggregates marrow for B lymphocytes and the thymus for T lymphocytes. called Hassall corpuscles, found only in the thymic medulla.  B cells produce antibodies for humoral immunity; T cells function in cell-mediated immunity. Mucosa-Associated Lymphoid Tissue (MALT)  T cells develop receptors (TCRs), usually containing α and β  MALT is found in the mucosa of most tracts but is chains, that bind antigen along with another surface protein concentrated in the palatine, lingual and pharyngeal tonsils, designated by a CD (“cluster of differentiation”) numbering Peyer patches, and the appendix. system.  Unlike MALT, lymph nodes are completely encapsulated and  Important classes of T cells include CD4+ T helper cells; CD8+ occur along the lymphatic vessels; each has several afferent cytotoxic T cells; CD4+ CD25+ regulatory T cells; and γδ T cells, lymphatics and one efferent lymphatic. which have those TCR chains and are mainly in epithelia.  B-cell receptors (BCRs) are IgM or IgD antibodies on the cell Lymph Nodes surface that bind specific antigens whenever they contact them.  Each lymph node filters lymph and provides a site for B-cell  B and T cells are often activated, proliferate, and begin to activation and differentiation to antibody-secreting plasma function in the secondary lymphoid organs: the lymph nodes, cells. all mucosaassociated lymphoid tissue (MALT), and the spleen.  A lymph node has three functional but not physically  In secondary lymphoid tissues, BCRs bind antigen not presented separate compartments: an outer cortex, a underlying in MHC class II molecules of another cell, the follicular dendritic paracortex, and an inner medulla adjacent to the hilum and cell (FDC). efferent lymphatic.  With cytokines from helper T cells, a FDC-activated B cell  Lymphatics enter at the cortex of a node, where B cells proliferates clonally to produce temporarily a large lymphoid encounter antigens, proliferate in lymphoid nodules, and nodule (or follicle), which develops a pale germinal center then move into the deeper regions of the lymph node.  From lymphoid nodules cells produced there disperse as plasma cells, various T cells, and B and T memory cells that respond Transcribers: Dalipe, Lagansoa 19 and proliferate quickly if their specific antigen reappears. Reference: Junqueira’s Basic Histology  HISTOLOGY | LYMPHOID ORGANS  Most lymphocytes enter at the paracortex of the lymph node via high endothelial venules (HEVs) located there only; most lymphocytes in this region are T helper cells.  The medulla has medullary cords containing reticular fibers with many plasma cells, macrophages, and other leukocytes; between the cords are lymph-filled medullary sinuses that converge at the efferent lymphatic. Spleen  The spleen is a large lymphoid organ without a cortex/medulla structure; instead, it has two intermingled but functionally different regions: white pulp and red pulp.  White pulp, only 20% of the spleen, is secondary lymphoid tissue associated with small central arterioles that are also enclosed by periarteriolar lymphoid sheaths (PALS) of T cells.  Red pulp, which filters blood, removes defective erythrocytes, and recycles hemoglobin iron, consists of splenic cords with macrophages and blood cells of all kinds and splenic sinusoids.  The splenic sinusoids are lined by unusual endothelial cells called stave cells that are elongated and aligned parallel to the blood flow,with open slits between the cells.  Blood flow in red pulp is either a closed circulation, moving from capillaries into the venous sinusoids, or an open circulation, with capillaries opening directly into the splenic cords.  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 Transcribers: Dalipe, Lagansoa 20 Reference: Junqueira’s Basic Histology