DOCSLIB.ORG

And Function in Aged Spleens Attrition of T Cell Zone Fibroblastic

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
And Function in Aged Spleens Attrition of T Cell Zone Fibroblastic Attrition of T Cell Zone Fibroblastic Reticular Cell Number and Function in Aged Spleens April R. Masters, Evan R. Jellison, Lynn Puddington, Kamal M. Khanna and Laura Haynes Downloaded from ImmunoHorizons 2018, 2 (5) 155-163 doi: https://doi.org/10.4049/immunohorizons.1700062 http://www.immunohorizons.org/content/2/5/155 This information is current as of September 24, 2021. http://www.immunohorizons.org/ Supplementary http://www.immunohorizons.org/content/suppl/2018/05/21/2.5.155.DCSupp Material lemental References This article cites 61 articles, 19 of which you can access for free at: http://www.immunohorizons.org/content/2/5/155.full#ref-list-1 Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: by guest on September 24, 2021 http://www.immunohorizons.org/alerts ImmunoHorizons is an open access journal published by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. ISSN 2573-7732. RESEARCH ARTICLE Adaptive Immunity Attrition of T Cell Zone Fibroblastic Reticular Cell Number and Function in Aged Spleens April R. Masters,*,† Evan R. Jellison,* Lynn Puddington,* Kamal M. Khanna,*,‡ and Laura Haynes*,† *Department of Immunology, UConn Health, Farmington, CT 06030; †Center on Aging, UConn Health, Farmington, CT 06030; and ‡Department of Microbiology, New York University, New York, NY 10003 Downloaded from ABSTRACT Aging has a profound impact on multiple facets of the immune system, culminating in aberrant functionality. The architectural disorganization http://www.immunohorizons.org/ of splenic white pulp is a hallmark of the aging spleen, yet the factors underlying these structural changes are unclear. Fibroblastic reticular cells comprise one stromal cell subset in the spleen that is important for maintenance of architectural organization, yet it remains to be determined how aging impacts these cells. In this study, we sought to determine how aging impacts splenic T cell zone reticular cell (TRC) numbers, morphology, and function. Using a mouse model of aging, we found that aged naive spleens have fewer TRCs than young spleens. This reduction in TRC number correlated with reduced CCL19 and CCL21 concentrations in aged spleens, which may contribute to impaired homing of T cells. CCL21 in both young and aged spleens localized with TRCs. Aged TRCs extended marginally into B cell follicles and may contribute to the blending of the T cell zone and B cell follicles in aged spleens. The described age-related changes in TRCs number and function may be an underlying factor contributing to impaired immune system function with age. ImmunoHorizons,2018,2:155–163. INTRODUCTION Nonhematopoietic stromal cells provide the framework and by guest on September 24, 2021 directional cues to optimize the organization of immune cells in Organization is a frequently overlooked component of an effective the splenic white pulp (12–14). In the spleen, there are multiple immune response (1). The likelihood of low-frequency, Ag-specific stromal cell subsets that localize to specificareas(15,16).The T cells interacting with the APC displaying their cognate Ag is splenic red pulp is populated with CXCL12-producing fibroblasts, amplified by multiple layers of organization, including secondary which can attract CXCR4-expressing effector T cells and plasma lymphoid organs (2–4). The spleen is one such organ located in the cells away from the white pulp (17, 18). Red pulp fibroblasts also upper right portion of the abdomen (5). The spleen is attached to facilitate clearance of dying RBCs and direct blood flow (16). Blood the vasculature (6) and is an important defense against bloodborne vessels, including central arterioles, are lined with the stromal cell pathogens like encapsulated bacteria (7, 8). Blood enters into the subset blood endothelial cells (BECs), which facilitate entry of cells spleen through blunt-ended central arterioles, which empty into and Ag into the splenic marginal zone (16). Fibroblastic reticular the marginal sinus surrounding the splenic white pulp (6). From cells (FRCs) are the most abundant variety of stromal cell in the the marginal sinus, immune cells can use bridging channels to splenic white pulp (19). Multiple subsets of FRCs exist that localize enter into the T cell zone (9). The T cell zone is surrounded by to specific regions of the splenic white pulp and have distinct highly segregated B cell follicles in which germinal centers can functional characteristics. FRCs can collectively be identified by develop and promote the production of high-affinity, class- their expression of the peptidoglycan podoplanin (PDPN), lack switched Ab responses (10, 11). of expression of the vasculature marker CD31, and lack of Received for publication October 25, 2017. Accepted for publication May 8, 2018. Address correspondence and reprint requests to: Dr. Laura Haynes, UConn Health, 263 Farmington Avenue, MC 1835, EM022, Farmington, CT 06030. E-mail address: [email protected] This work was supported by National Institute on Aging Program Grant AG021600 and the UConn Health Center on Aging. Abbreviations used in this article: BEC, blood endothelial cell; DNC, double-negative cell; FDC, follicular dendritic cell; FRC, fibroblastic reticular cell; KO, knockout; PDPN, podoplanin; TRC, T cell zone reticular cell. The online version of this article contains supplemental material. This article is distributed under the terms of the CC BY-NC 4.0 Unported license. Copyright © 2018 The Authors https://doi.org/10.4049/immunohorizons.1700062 155 ImmunoHorizons is published by The American Association of Immunologists, Inc. 156 IMPACT OF AGING ON SPLENIC FIBROBLASTIC RETICULAR CELLS ImmunoHorizons hematopoietic lineage maker CD45 (16, 20). Marginal zone retic- EDTA (Invitrogen) and 13 Halt protease and phosphatase ular cells are a MADCAM-1–expressing FRC subset that localize to inhibitor mixture (Thermo Fisher). Homogenates were centri- the marginal zone. These cells produce CXCL13 and may facilitate fuged at 1000 3 g for 10 min, and supernatants were aliquoted and trafficking of Ag into B cell follicles (21). T cell zone reticular frozen at 280°C until analysis. CCL21 was measured using mouse cells (TRCs) form a lattice-like conduit network in the bridging CCL21/6Ckine DuoSet ELISA (R&D Systems). CCL19 was channels and T cell zone upon which Ag, lymphocytes, and measured using mouse CCL19/MIP-3 beta DuoSet ELISA (R&D dendritic cells traffic (9, 14, 22). TRCs produce the homeostatic Systems). Chemokine concentrations were normalized to total chemokines CCL19 and CCL21, which bind to CCR7-expressing protein concentration, determined using Pierce BCA Protein cells to direct them into the T cell zone (12, 23, 24). A specialized Assay (Thermo Fisher). subset for FRCs called follicular dendritic cells (FDCs) are located in the B cell follicles. FDCs produce the chemokine CXCL13, which T cell transfer + interacts with CXCR5 on B cells and T follicular helper cells to CD8 T cells were isolated from pooled spleens and lymph nodes of + direct them to the B cell follicle (25). FDCs also trap Ag and provide CD45.1 F5 RAG KO mice using MojoSort Mouse CD8 T cell ’ cues to help B cells in the production of high-affinity Abs (26–28). Isolation Kit (BioLegend) according to the manufacturer s + Downloaded from It is well established that aging leads to disorganized splenic instructions. Before transfer, the purity of the isolated CD8 fi 3 6 + architecture, characterized by merging of cells in the B cell Tcellswascon rmed at 85% or above. A total of 2.3 10 CD8 follicles and T cell zone (29–33). Yet it is less clear how aging T cells in 200 ml PBS were injected via the tail vein into each mouse. fi impacts the stromal cells underlying this organization (34). Mice were sacri ced exactly 30 min after transfer for analysis. Although several studies have described age-related attrition of Immunofluorescence FDC function and morphology (35–38), it largely remains to be Spleens were fixed overnight in medium containing 0.05 M http://www.immunohorizons.org/ determined how aging impacts splenic TRCs. In this study, we phosphate buffer, 0.1 M L-lysine (pH 7.4), 2 mg/ml NaIO ,and sought to characterize how aging impacts the number, morphol- 4 10 mg/ml paraformaldehyde and then dehydrated with 30% ogy, and function of splenic TRCs to further our understanding of sucrose in phosphate buffer (33). Spleens were frozen in Tissue- the aging immune system. Tek O.C.T. Compound (Sakura Finetek), and 20-mm sections were Our results reveal that aged spleens have fewer TRCs and cut using a CM1850 Cryostat (Leica). Sections were blocked for decreased T cell zone areas. Concomitant with the reduction of 30minwith2%goatserumandstainedovernightat4°Cina TRC number, homeostatic chemokine levels are reduced in aged humidified chamber with the following primary Ab mixture: anti- spleens, correlating with impaired recruitment of young T cells. PDPN clone 8.1.1 unconjugated (Origene) (1:300 dilution), anti-B220 Interestingly, CCL21 largely colocalizes with TRCs and appears to PE-Dazzle AF594 clone RA3-6BP (BioLegend) (1:100 dilution), extend slightly into the B cell follicles in aged but not young anti-CD31 AF647 clone MEC13.3 (BioLegend) (1:100 dilution), and by guest on September 24, 2021 spleens. Reduction of TRC number and homeostatic chemokine anti-CD8a BV421 clone 53.6.7 (BioLegend) (1:100 dilution) in 2% concentrations may contribute to altered splenic architecture and goat serum. Sections were then washed in PBS and stained for 2 h impaired T cell homing found in aged spleens. at room temperature with goat anti-hamster AF488 (Invitrogen) (1:400 dilution). For detection of CCL21, sections were blocked as described and stained overnight with biotinylated anti-CCL21 Ab MATERIALS AND METHODS (R&D) (1:20 dilution) in 2% goat serum with 0.3% Triton X-100 (Sigma-Aldrich). After PBS washes, CCL21 signal was amplified Mice using Alexa Fluor 594 Tyramide SuperBoost Kit and streptavidin Aged (18–20mo)maleC57BL/6Jmicewereobtainedfromthe (Thermo Fisher) according to manufacturer’s instructions.
Load more

Recommended publications
  • Pulp Border in L1-Deficient Mice Selective Malformation of the Splenic White
    Selective Malformation of the Splenic White Pulp Border in L1-Deficient Mice Shih-Lien Wang, Michael Kutsche, Gino DiSciullo, Melitta Schachner and Steven A. Bogen This information is current as of September 27, 2021. J Immunol 2000; 165:2465-2473; ; doi: 10.4049/jimmunol.165.5.2465 http://www.jimmunol.org/content/165/5/2465 Downloaded from References This article cites 45 articles, 12 of which you can access for free at: http://www.jimmunol.org/content/165/5/2465.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 27, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Selective Malformation of the Splenic White Pulp Border in L1-Deficient Mice1 Shih-Lien Wang,* Michael Kutsche,† Gino DiSciullo,* Melitta Schachner,† and Steven A. Bogen2* Lymphocytes enter the splenic white pulp by crossing the poorly characterized boundary of the marginal sinus. In this study, we describe the importance of L1, an adhesion molecule of the Ig superfamily, for marginal sinus integrity.
    [Show full text]
  • 201028 the Lymphatic System 2 – Structure and Function of The
    Copyright EMAP Publishing 2020 This article is not for distribution except for journal club use Clinical Practice Keywords Immunity/Anatomy/Stem cell production/Lymphatic system Systems of life This article has been Lymphatic system double-blind peer reviewed In this article... l How blood and immune cells are produced and developed by the lymphatic system l Clinical significance of the primary and secondary lymphoid organs l How the lymphatic system mounts an immune response and filters pathogens The lymphatic system 2: structure and function of the lymphoid organs Key points Authors Yamni Nigam is professor in biomedical science; John Knight is associate The lymphoid professor in biomedical science; both at the College of Human and Health Sciences, organs include the Swansea University. red bone marrow, thymus, spleen Abstract This article is the second in a six-part series about the lymphatic system. It and clusters of discusses the role of the lymphoid organs, which is to develop and provide immunity lymph nodes for the body. The primary lymphoid organs are the red bone marrow, in which blood and immune cells are produced, and the thymus, where T-lymphocytes mature. The Blood and immune lymph nodes and spleen are the major secondary lymphoid organs; they filter out cells are produced pathogens and maintain the population of mature lymphocytes. inside the red bone marrow, during a Citation Nigam Y, Knight J (2020) The lymphatic system 2: structure and function of process called the lymphoid organs. Nursing Times [online]; 116: 11, 44-48. haematopoiesis The thymus secretes his article discusses the major become either erythrocytes, leucocytes or hormones that are lymphoid organs and their role platelets.
    [Show full text]
  • Lymphoid Tissue and Lymphatic Organs Defense Mechanisms
    Lymphoid Tissue and Lymphatic Organs Defense Mechanisms Innate / Non-specific Adaptive / Specific Epithelial Barriers Humoral Immune reaction (B cells) Cell-mediated immune reaction (T cells) Phagocytic cells Pattern Recognition Receptors Acute inflammation Neutrophils, Macrophages, Mast cells, other granulocytes NK cells Antigen Presenting Cells (APCs) Complement system Pattern Recognition Receptors Innate (non-specific) immune system Recognize molecular patterns Found on phagocytes Types Endocytic PRRs Signaling PRRs Toll-like receptors (TLRs) CD 14 receptor NOD receptor Natural Killer cells (NK cells) Adaptive / Specific Some Definitions Antigen Self: Major Histocompatibility Complex (MHC) – I and II Non-self: Foreign Epitope Antibody IgG, IgM, IgD, IgE, IgA Adaptive Immune System: Cells B cells Humoral immune response B cells receptors: Immunoglobulins (antibodies) T cells T cytotoxic cell (CD8+) Cell-mediated immune response T helper cell (CD4+) Active in initial phase of both types Antigen Presenting Cells (APCs) Professional Non Professional Lymphoid Tissue Reticular connective tissue Network of reticular fibers Network of stellate reticular cells Fibroblasts, Macrophages, Dendritic cells Very numerous lymphocytes Localization of Lymphoid Tissue Lymphatic Organs Lymph node Spleen Thymus Mucosa-Associated Lymphoid Tissue (MALT) Tonsils GALT BALT (Bronchi-Associated LT) Types of Lymphoid Tissue Diffuse: B and T cells Nodular (Follicular): Mainly B cells Spherical aggregates of lymphoid tissue Primary and secondary B cell selection Follicular Dendritic cells Th cells Macrophages Lymph Node Spleen White pulp PALS (T cells) Splenic (lymphoid) nodules (B cells) Red pulp Splenic cords Splenic Sinusoids Pulpal veins Primary follicle Thymus Epithelial origin No reticular connective tissue Only T cells No lymphoid nodules No immune reactions against non-self antigens T cell school Thymus Thymus Autoimmunity Involution .
    [Show full text]
  • Lymphoid System IUSM – 2016
    Lab 14 – Lymphoid System IUSM – 2016 I. Introduction Lymphoid System II. Learning Objectives III. Keywords IV. Slides A. Thymus 1. General Structure 2. Cortex 3. Medulla B. Lymph Nodes 1. General Structures 2. Cortex 3. Paracortex 4. Medulla C. MALT 1. Tonsils 2. BALT 3. GALT a. Peyer’s patches b. Vermiform appendix D. Spleen 1. General Structure 2. White Pulp 3. Red Pulp V. Summary SEM of an activated macrophage. Lab 14 – Lymphoid System IUSM – 2016 I. Introduction Introduction II. Learning Objectives III. Keywords 1. The main function of the immune system is to protect the body against aberrancy: IV. Slides either foreign pathogens (e.g., bacteria, viruses, and parasites) or abnormal host cells (e.g., cancerous cells). A. Thymus 1. General Structure 2. The lymphoid system includes all cells, tissues, and organs in the body that contain 2. Cortex aggregates (accumulations) of lymphocytes (a category of leukocytes including B-cells, 3. Medulla T-cells, and natural-killer cells); while the functions of the different types of B. Lymph Nodes lymphocytes vary greatly, they generally all appear morphologically similar so cannot be 1. General Structures routinely distinguished in light microscopy. 2. Cortex 3. Lymphocytes can be found distributed throughout the lymphoid system as: (1) single 3. Paracortex cells, (2) isolated aggregates of cells, (3) distinct non-encapsulated lymphoid nodules in 4. Medulla loose CT associated with epithelium, or (4) encapsulated individual lymphoid organs. C. MALT 1. Tonsils 4. Primary lymphoid organs are sites where lymphocytes are formed and mature; they 2. BALT include the bone marrow (B-cells) and thymus (T-cells); secondary lymphoid organs are sites of lymphocyte monitoring and activation; they include lymph nodes, MALT, and 3.
    [Show full text]
  • The Splenic T Cell Zone Within Lymphocyte Entry Into And
    Fibroblastic Reticular Cells Guide T Lymphocyte Entry into and Migration within the Splenic T Cell Zone This information is current as Marc Bajénoff, Nicolas Glaichenhaus and Ronald N. of September 24, 2021. Germain J Immunol 2008; 181:3947-3954; ; doi: 10.4049/jimmunol.181.6.3947 http://www.jimmunol.org/content/181/6/3947 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2008/08/29/181.6.3947.DC1 Material References This article cites 41 articles, 16 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/181/6/3947.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 24, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Fibroblastic Reticular Cells Guide T Lymphocyte Entry into and Migration within the Splenic T Cell Zone1 Marc Baje´noff,*†‡ Nicolas Glaichenhaus,† and Ronald N.
    [Show full text]
  • Lymphoid Tissue
    Lymphoid Tissue Dr Punita manik Professor Department of Anatomy K G’s Medical University U P Lucknow Classification • Diffuse Lymphoid tissue: diffuse arrangement of lymphocytes and plasma cells deep to epithelium in Lamina propria of digestive, respiratory and urogenital tracts forming an immunological barrier against invasion of microorganisms. • Dense Lymphoid tissue: presence of lymphocytes in the form of nodules Classification Dense Lymphoid Tissue: Nodules are found either in association with mucous membranes of viscera or as discrete encapsulated organs. 2 Types 1. MALT(Mucosa associated Lymphoid Tissue; Nonencapsulated) 2. Discrete Lymphoid organs (Encapsulated) • MALT: Solitary Nodules Aggregated Nodules(Peyer’s patches) Lymphoid nodules in vermiform appendix Waldeyer’s ring at the entrance of pharynx • Discrete Lymphoid Organs: Thymus Lymph Node Spleen Tonsil Lymph Node • Connective tissue framework Capsule Trabecula Reticular Stroma (fibres) Components of Lymph Node • Parenchyma 1.Cortex 2.Paracortex (Inner Cortex) 3.Medulla Lymph node Lymph Node Reticulum • Reticular stroma- reticular fibres and phagocytic reticular cells • Gives structural support to the lymphoid cells Lymph Node Reticulum Cortex Subcapsular Sinus Lymphatc Nodules Primary Nodule Secondary Nodule Germinal Centre • Paracotex: Inner cortical Zone Thymus dependent zone Lymph Node • Medulla: • Medullary Cords -Darkly stained, branching anastomosing – B Lymphocytes, plasma cells& macrophages • Medullary Sinuses- Lightly stained Lymph Node Lymph Node Lymph Node Thymus • Central Lymphoid organ • Dual Origin- Lymphoctes- Mesoderm • Reticular epithelial cells- Endoderm • Formed only by T lymphocytes • No B lymphocytes • Divided into lobules of lymphoid tissue( No lymphatic nodule) • Has hassall’s corpuscles • Produces thymic hormones • Fully dev at birth, involutes at puberty. Thymus • COMPONENTS 1. Supporting Framework Capsule Interlobular septa Cellular cytoplasmic reticulum 2.
    [Show full text]
  • Lymphomas in the Spleen
    Lymphomas in the Spleen 1/21/2014 Outline Normal histology of the spleen Lymphomas in the spleen: -Splenic marginal zone lymphoma (0.9% of B cell lymphomas) -Hepatosplenic T cell lymphoma (1.4% of T cell lymphomas) -Splenic B cell lymphoma/leukemia, unclassifiable (provisional entity) -Other lymphomas (not covered here) Case studies NORMAL HISTOLOGY OF THE SPLEEN Gross Anatomy Normal weight 150 g, SD 25 g Hilus, where it is penetrated by vessels and nerves which follow the extensive branching network of fibrous trabeculae. Accessory spleens occur in about 10 percent of individuals Following traumatic rupture, small nodules of splenic tissue may grow on the peritoneal surface as implants (splenosis) Normal spleen White Pulp Comprises the lymphoid compartment of the spleen and consists of both follicular B-cell- rich areas as well as T-cell-rich periarteriolar lymphoid sheaths. Primary and Secondary B-Cell Follicles MARGINAL ZONE Surrounds the primary follicle and the mantle zone of secondary follicles Consists of a corona of medium-sized lymphoid cells with prominent pale cytoplasm Spleen: Periarteriolar area The T cells predominate in the periarteriolar lymphoid sheath (labeled red with Leu-22/ CD43). The follicles, which tend to occur at arterial branch points, are labeled blue (L26/CD20). Sinusoids . Are lined by tapered endothelial cells separated by slit-like spaces and surrounded by distinctive ring fibers and bridging fibers . Stain endothelial markers (FVIII) PAS stain highlights the distinctive ring fibers and bridging fibers Splenic macrophages Macrophages are preferentially located in the marginal zone and red pulp cords of the spleen (labeled brown with KP- 1/CD68).
    [Show full text]
  • Immunology Pre-Matriculation Review Answers the Answers to the Questions Are Shown in Blue Text. 1. One Reason That Pathogenic M
    Immunology Pre-Matriculation Review Answers The answers to the questions are shown in blue text. 1. One reason that pathogenic microorganisms have an advantage in the host they infect is because they: a) have previously been encountered through natural exposure b) have previously been encountered through vaccination c) strengthen the host’s immune response d) reproduce and evolve more rapidly than the host can eliminate them e) reproduce and evolve more slowly than the host can eliminate them. 2. Examples of pathogens that cause human disease include: a) bacteria b) viruses c) fungi d) parasites (protozoans and worms) e) All of the above are examples of pathogens that cause human disease. 3. Which of the following is not associated with mucosal surfaces? a) mucus-secreting goblet cells b) lysozyme c) M cells d) white pulp e) beating cilia 4. Which of the following is not a characteristic of inflammation? a) inactivation of macrophages b) increased vascular permeability and edema c) vasodilation d) pain e) influx of leukocytes 5. Phagocytosis of either microbes or microbial constituents by macrophages is followed by the activation of macrophages and the secretion of cytokines. What are the main effects of these molecules? The cytokines released by activated macrophages have three principal effects. Some cytokines act as chemoattractants and recruit other leukocytes into the infected tissue, for example neutrophils, which efficiently phagocytose and kill bacteria, forming pus. Other cytokines act on the endothelial cells of local blood vessels to increase vascular permeability and vasodilation, thus initiating inflammation of the infected tissue. 6. Identify the different anatomical locations where hematopoiesis occurs in embryonic, fetal, and adult life.
    [Show full text]
  • Hematopoiesis- Formation
    Chapter 2. Cells and Organs of the Immune System Hematopoiesis • Hematopoiesis - formation and development of WBC and RBC bone marrow. • Hematopoietic stem cells (HSC)- give rise to any blood cells (constant number, self renewing) • Yolk sac (2 months) liver & spleen (3- 7 months) Bone marrow (birth) Hematopoiesis • Progenitor commitment depends on the influence of growth factors and cytokines • In bone marrow stromal cells support the growth and differentiation of hematopoietic cells direct 1 2 contact or growth factors. 3 • Stromal cells – meshwork of fat cells, endothelial cells, fibroblasts & M Φs. • Hematopoiesis – regulated at the genetic level through several transcription factors (GATA-2, Ikaros, Bmi-1, etc) Hematopoiesis Apoptosis • Hematopoiesis maintains steady levels of blood cells • Programmed cell death • 3.7 x 10 11 cells/day!!! • Changes: shrinking, rearrangement of • Regulation: cytoskeleton, alteration of cell membrane permeability, chromatin condensation, – Cytokines produced by bone marrow stromal cells cytoplasm fragmentation – Cytokines produced by non-hematopoietic cells (T cells, M Φs) – Regulation of receptors for hematopoietically • Difference between apoptosis and necrosis? active cytokines – Removal of cells by programmed cell death 1 bcl - B cell lymphoma Cells of the Immune System Bcl-2 prevents apoptosis ? (Apoptosis) (Immune Response) ↓ Bcl-2 ↑ bax Separation of blood constituents - If heparinized blood is centrifuged, three layers are obtained: ••• Top layer - yellow liquid - plasma ••• Middle layer
    [Show full text]
  • Lymphatic System
    OUTLINE 24.1 Functions of the Lymphatic System 725 24.2 Lymph and Lymph Vessels 726 24 24.2a Lymphatic Capillaries 726 24.2b Lymphatic Vessels 726 24.2c Lymphatic Trunks 727 24.2d Lymphatic Ducts 727 Lymphatic 24.3 Lymphatic Cells 729 24.3a Types and Functions of Lymphocytes 729 24.3b Lymphopoiesis 734 24.4 Lymphatic Structures 735 System 24.4a Lymphatic Nodules 735 24.4b Lymphatic Organs 736 24.5 Aging and the Lymphatic System 741 24.6 Development of the Lymphatic System 741 MODULE 10: LYMPHATIC SYSTEM mck78097_ch24_724-746.indd 724 2/25/11 2:16 PM Chapter Twenty-Four Lymphatic System 725 e have seen in chapters 21–23 how the cardiovascular system W transports blood throughout the body, where it exchanges gases and nutrients with the tissues. Another body system, called the lymphatic system, aids the cardiovascular system by transporting excess interstitial fluid through lymph vessels assisting in maintain- ing fluid homeostasis. Once this fluid enters the vessels, the fluid is Tonsils renamed lymph. Along the way, lymph is filtered and checked for Cervical lymph nodes foreign or pathologic material, such as bacteria and cancer cells. Right lymphatic duct Lymphatic structures contain certain cells that initiate an immune Axillary response to abnormal materials. Without the primary immune Thymus response by the lymphatic system, the body would be unable to fight lymph nodes infection and keep itself healthy. In this chapter we examine the lymph vessels, lymphatic Thoracic duct structures, and lymphatic organs of the body, and learn how each Spleen Cisterna chyli of these components plays an important role in keeping us healthy.
    [Show full text]
  • Extramedullary Hematopoiesis: Elucidating the Function of the Hematopoietic Stem Cell Niche (Review)
    MOLECULAR MEDICINE REPORTS 13: 587-591, 2016 Extramedullary hematopoiesis: Elucidating the function of the hematopoietic stem cell niche (Review) KOUHEI YAMAMOTO1, YUKAKO MIWA2, SHIHO ABE-SUZUKI1, SHINYA ABE1, SUSUMU KIRIMURA1, IICHIROH ONISHI1, MASANOBU KITAGAWA1 and MORITO KURATA1 1Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo‑ku, Tokyo 113‑8519; 2Department of Pathology, Kanazawa Medical University Hospital, Kanazawa, Ishikawa 920‑0293, Japan Received May 6, 2014; Accepted February 11, 2015 DOI: 10.3892/mmr.2015.4621 Abstract. Extramedullary hematopoiesis (EMH) occurs Contents under various circumstances, including during embry- onic/developmental periods, pathological status secondary to 1. Introduction insufficient bone marrow function or ineffective hematopoi- 2. Sites of EMH esis, in hematological disorders, for example malignancies, 3. Embryonic/developmental EMH as well as stromal disorders of the bone. EMH is character- 4. EMH associated with hematological disorders ized by hematopoietic cell accumulations in multiple body 5. EMH associated with stromal abnormalities locations. Common EMH locations observed in clinical and 6. Microenvironment of EMH pathological practice include the spleen, liver, lymph nodes 7. Conclusion and para‑vertebral regions. Among the various organs associ- ated with EMH, the spleen offers a unique site for evaluation of hematopoietic stem cell (HSC)/niche interactions, as this 1. Introduction organ is one of the most common sites of EMH. However, the spleen does not have a major role in embryonic/developmental Extramedullary hematopoiesis (EMH) is characterized by hematopoiesis. A recent study by our group revealed that the formation and development of blood cells, external to circulating HSCs may be trapped by chemokine (C-X-C motif) the bone marrow medullary spaces.
    [Show full text]
  • Hematolymphoid-System.Pdf
    Toxicologic Pathology 2019, Vol. 47(6) 665-783 ª The Author(s) 2019 Nonproliferative and Proliferative Article reuse guidelines: sagepub.com/journals-permissions Lesions of the Rat and Mouse DOI: 10.1177/0192623319867053 journals.sagepub.com/home/tpx Hematolymphoid System 1 2,c Cynthia L. Willard-Mack, (Chair) , Susan A. Elmore , 3 4,e,g 5,f William C. Hall , Johannes Harleman , C. Frieke Kuper , 6,a 7,d,g 8,g Patricia Losco , Jerold E. Rehg , Christine Ru¨ hl-Fehlert , 9,d,g 10,b 11 Jerrold M. Ward , Daniel Weinstock , Alys Bradley , 12 13 14 Satoru Hosokawa , Gail Pearse , Beth W. Mahler , 2 15 Ronald A. Herbert , and Charlotte M. Keenan Abstract The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative changes in rats and mice. The purpose of this publication is to provide a standardized nomenclature for classifying changes observed in the hematolymphoid organs, including the bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissues, and other lymphoid tissues (serosa-associated lymphoid clusters and tertiary lymphoid structures) with color photomicrographs illustrating examples of the lesions. Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. The nomenclature for these organs is divided into 3 terminologies: descriptive, conventional, and enhanced.
    [Show full text]