(BQ) Part 1 book BRS Cell biology and histology presents the following contents: Plasma membrane, nucleus, cytoplasm and organelles, extracellular matrix, epithelia and glands, connective tissue, cartilage and bone, muscle, nervous system, blood and hemopoiesis, circulatory system,...
Cell Biology and Histology SEVENTH EDITION Leslie P Gartner, PhD Professor of Anatomy (Retired) Department of Biomedical Sciences University of Maryland Dental School Baltimore, Maryland James L Hiatt, PhD Professor Emeritus Department of Biomedical Sciences University of Maryland Dental School Baltimore, Maryland ERRNVPHGLFRVRUJ đWolters Kluwer Health Philadelphia Baltimore • New York • London Buenos Aires· Hong Kong· Sydney· Tokyo Acquisitions Editor: Crystal Taylor Product Development Editor: Amy Weintraub Production Project Manager: Priscilla Crater Design Coordinator: Holly Reid McLaughlin Manufacturing Coordinator: Margie Orzech Compositor: S4Carlisle Publishing Services Copyright© 2015 Wolters Kluwer Health 351 West Camden Street Baltimore, MD 21201 Two Commerce Square, 200 Market Street Philadelphia, PA 03 Copyright© 20 1, 2007, 2003, 1998, 1993, 988 Lippincott Williams & Wilkins, a Wolters Kluwer business Korean Translation, 2005, published by ShinHeung Medscience, Inc Spanish Translation, 2008, published by Lippincott Williams & Wilkins Japanese translation, 2007, published by Medical Sciences International, LTD Greek translation, 2006, published by Parissianos Publishing Company All rights reserved This book is protected by copyright No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner The publisher is not responsible (as a matter of product liability, negligence, or otherwise) for any injury resulting from any material contained herein This publication contains information relating to general principles of medical care that should not be construed as specific instructions for individual patients Manufacturers' product information and package inserts should be reviewed for current information, including contraindications, dosages, and precautions Printed in China Library of Congress Cataloging-in-Publication Data Gartner, Leslie P., 1943- author Cell biology and histology I Leslie P Gartner, James L Hiatt - Seventh edition p ; em - (Board review series) Includes bibliographical references and index ISBN 978- 1-45 1 -895 1-3 (paperback :alk paper) I Hiatt, James L., 1934- author II Title III Series: Board review series [DNLM: l Histological Techniques-Outlines Cytological Techniques-Outlines QS 8.2] QM553 1'.018-dc23 2014018636 DISCLAIMER Care has been taken to confirm the accuracy of the information present and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of this information in a particular situation remains the professional responsibility of the practitioner; the clinical treatments described and recommended may not be considered absolute and universal recommendations The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with the current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to {301) 223-2320 International customers should call {301) 223-2300 Visit Lippincott Williams & Wilkins on the Internet: http:/ /www.lww.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST Preface We were very pleased with the reception of the sixth edition of this book, as well as with the many favorable comments we received from students who used it in preparation for the U SMLE Step l or as an outline and study guide for their histology and/or cell biology courses in professional schools or undergraduate colleges Many of the chapters have been extensively revised and updated to incorporate current information, and we have attempted to refine the content of the text to present material emphasized on National Board Examinations as succinctly as possible while still retaining the emphasis on the relationship between cell structure and function through the vehicle of cell and molecular biology A tremendous amount of material has been compressed into a concise but highly comprehensive presentation, using some new and revised illustrations The relevancy of cell biology and histology to clinical practice is illustrated by the presence of clinical considerations within each chapter as appropriate The greatest changes that occurred in the evolution of this book from its previous edi tion are that we have added many more clinical considerations and compressed informa tion into tabular form We believe that these changes make this board review book more interesting and pertinent and the presentation of material in tables conserves time in the review process for medical students in their preparation for the USMLE Step l We are sad to announce that Judy Strum, our coauthor throughout the first six editions of this review book, decided to complete her retirement from the faculty of the University of Maryland School of Medicine thereby withdrawing her participation in the preparation of the current edition of this textbook As always, we welcome comments, suggestions, and constructive criticism of this book Please address all comments to LP G2ll36@yahoo.com Leslie P Gartner, PhD James L Hiatt, PhD iii Acknowledgments We thank the following individuals for their help and support during the preparation of this book: Crystal Taylor, our Acquisitions Editor; and Dana Battaglia and Amy Weintraub, our product Development Editor(s), who helped us weave all of the loose ends into a seamless whole iv Contents Preface iii Acknowledgments iv PLASMA MEMBRANE I Overview-The Plasma Membrane (Plasmalemma; Cell Membrane) II Ill IV V Fluid Mosaic Model of the Plasma Membrane Plasma Membrane Transport Processes Cell-to-Cell Communication I v VI VII VIII IX X XI 15 Overview- The Nucleus Nuclear Envelope Chromatin 18 19 Chromosomes DNA 21 RNA 22 Cell Cycle 15 15 18 Nucleolus Nucleoplasm 20 25 Apoptosis (Programmed Cell Death) Meiosis Review Test I 31 Overview-The Cytoplasm Structural Components 33 33 33 Interactions among Organelles Review Test 28 29 CYTOPLASM AND ORGANELLES II Ill 12 NUCLEUS II Ill IV Plasmalemma-Cytoskeleton Association Review Test 1 49 58 v vi Contents EXTRACELLULAR MATRIX I II Ill Overview-The Extracellular Matrix Ground Substance Fibers Review Test v 72 75 Overview-Epithelia 75 77 Basal Epithelial Surfaces 80 Apical Epithelial Surfaces 83 87 Glands 89 CONNECTIVE TISSUE I II Ill IV 92 92 Overview-Connective Tissue Extracellular Matrix 92 Connective Tissue Cells 93 Classification of Connective Tissue Review Test Overview-Bone Review Test 106 106 Overview-Cartilage Joints llO 120 21 MUSCLE I II Ill IV v VI VI I 124 Overview-Muscle 124 Structure o f Skeletal Muscle 124 Contraction o f Skeletal Muscle 130 Innervation of Skeletal Muscle 132 Cardiac Muscle 133 Smooth Muscle 135 Contractile Nonmuscle Cells Review Test 99 03 CARTILAGE AND BONE I II Ill 64 Lateral Epithelial Surfaces Review Test 61 61 EPITHELIA AND GLANDS I II Ill IV 61 40 139 Contents NERVOUS SYSTEM I II Ill IV v VI VII VIII IX X XI Overview-Nervous System 143 143 145 Cells o f Nervous System 151 Synapses Nerve Fibers 152 153 Ganglia 155 Histophysiology o f Nervous System 155 Somatic Nervous System and Autonomic Nervous System Degeneration and Regeneration of Nerve Tissue 160 162 BLOOD AND HEMOPOIESIS I II Ill IV V VI VII 157 15 Central Nervous System Review Test 10 143 Histogenesis o f the Nervous System Nerves vii Overview-Blood 166 Blood Constituents 166 Blood Coagulation 172 Bone Marrow 166 174 Prenatal Hemopoiesis 175 Postnatal Hemopoiesis 175 Hemopoietic Growth Factors ( CSFS ) 179 Review Test 181 11 I II Overview-Blood Vascular System 184 Overview-Lymphatic Vascular System Review Test 12 184 CIRCULATORY SYSTEM 195 196 199 LYMPHOID TISSUE I II Ill IV V VI Overview-The Lymphoid ( Immune ) System Cells of the Immune System 199 201 Antigen Presentation and the Role of MHC Molecules Immunoglobulins 210 Diffuse Lymphoid Tissue Lymphoid Organs Review Test 218 212 211 209 viii 13 Contents ENDOCRINE SYSTEM I II Ill IV V VI VI I Overview-The Endocrine System Hormones Overview-Thyroid Gland Parathyroid Glands v VI 232 Overview-Adrenal (Suprarenal) Glands Pineal Gland (Pineal Body, Epiphysis) 234 237 239 242 Overview-The Skin Epidermis Dermis 242 242 248 Glands in the Skin 249 Hair, Hair Follicle, and Arrector Pili Muscle Nails Review Test 251 252 254 RESPIRATORY SYSTEM I II Ill IV V VI 222 228 SKIN I II Ill IV 15 221 221 Overview-Pituitary Gland (Hypophysis) and Hypothalamus Review Test 14 221 257 Overview-The Respiratory System 25 Conducting Portion of the Respiratory System 25 Overview-Respiratory Portion of the Respiratory System Lung Lobules 262 269 Pulmonary Vascular Supply Pulmonary Nerve Supply 269 269 Review Test 270 16 DIGESTIVE SYSTEM: ORAL CAVITY AND ALIMENTARY TRACT I II Ill IV Overview-The Digestive System Oral Region Divisions of the Alimentary Canal Digestion and Absorption Review Test 291 273 273 289 278 273 Contents 17 DIGESTIVE SYSTEM: GLANDS I II Ill IV V Overview-Pancreas Liver I 309 309 Overview-The Urinary System 309 Uriniferous Tubules 310 Renal Blood Circulation 320 Regulation of Urine Concentration Excretory Passages 321 324 327 FEMALE REPRODUCTIVE SYSTEM I II Ill IV V VI VII VIII IX X Overview-Female Reproductive System Ovaries Oviducts (Fallopian Tubes ) 339 330 Cervix 341 338 Fertilization and Implantation Placenta Vagina 330 330 Uterus 342 343 345 External Genitalia (Vulva ) Mammary Glands Review Test 20 304 306 Kidneys Review Test 19 296 THE URINARY SYSTEM II Ill IV V VI 345 346 348 MALE REPRODUCTIVE SYSTEM I II Ill IV V VI Overview-Male Reproductive System Testes 350 Genital Ducts 357 Accessory Genital Glands Urethra Penis Review Test 294 294 299 Gallbladder Review Test 18 294 Overview-Extrinsic Glands of the Digestive System Major Salivary Glands ix 361 362 363 359 350 350 BRS Cell B iology and H istology 206 t a b I e 12.2 Biological Activities of Selected Cytokines in the I m m u n e Response* Cytokine Secreted by Target Cell Actio n I L- a, I L- b M a c ro p h a g e s a n d e p ith e l i a l c e l l s T c e l ls, m a c ro p h a g e s Activates both T lym p h o cytes and m a c r o p h a g e s I L-2 T" c e l l s Activated T c e l l s , B c e l l s I n d u c e s m itosis o f a ctivated T a n d B c e l l s I L-4 T" c e l l s B cells I n d u c e s mitosis o f B c e lls, th e i r tra nsformation i nto p l a s m a c e l ls; promotes isotype switc h i n g fro m l g M t o l g G a n d l g E I L-5 T" c e l l s B cells I n d u c e s mitosis, maturation of B c e l l s ; promotes isotyp e switc h i n g from lgM to l g E I L-6 Anti g e n - p resenting c e l l s a n d T"2 c e l l s T c e l ls, a ctivate d B c e l l s Activates T c e lls, i n d u c e s m aturation o f B c e l l s t o l g G -fo rming p l a s m a c e l l s I L- T" c e l l s T"1 cells I n h i b its formation of T" c e lls; reta rds their a b i l ity to m a n ufacture cytokines I L- B c e l l s, m a c ro p h a g e s N K c e l ls, T c e l l s Activates N K c e l ls, fa c i l itates formation of T" - like c e l l s I L- S Macrophages T"1 cells and N K cells Acts on T " c e l l s to p ro d u c e I F N -y a n d e n h a n c e s N K c e l l a ctivity I L-23 M a c ro p h a g es CDS+ T cells d e c reases the motil ity of C D S + T c e l l s TN F-a M a c ro p h a g e M a c ro p h a g e s M a c ro p h a g e s se lf-a ctivate t o m a n ufacture, release I L- T" c e l l s Activated m a c ro p h a g e s Promotes p rod u ction o f oxyg e n r a d i c a l s fa c i l itatin g b a cterial ki l l i n g with i n endosomes of a ctivated m a c ro p h a g es I N F-a Virally atta c k e d c e l l s N K c e l ls, m a c r o p h a g e s Activates m a c ro p h a g es, N K c e l l s I N F-p Virally atta c k e d cells N K c e l ls, m a c ro p h a g e s Activates m a c ro p h a g es, N K c e l l s I F N -y T" c e l l s M a c ro p h a g es, T c e l l s Activates cytotoxic T c e l l s t o kill a ltered a n d/ or fore i g n c e l ls; promotes p h a g o cytosis by m a c ro p h a g es lg, immunoglobulin; I L i nterleukin; I N F interferon; NK natural killer; T", T helper; TNF, tumor necrosis factor *See Chapter 10 for discussion of cytokines involved in hemopoiesis (2) T cytotoxic cells are CDS+ cells After priming by an antigenic stimulus via an APC, T cells are induced by I L-2 to proliferate, forming new CTLs, which mediate (via perforins and g ranzymes) apoptosis of foreign cells as well as virally altered self-cells (Figure ) (3) T reg cells (previously called T suppressor cells) are CD4+ cells T reg cells are o f two types, natural and inducible (a) Natura l T reg cells (nT reg cel ls) originate in the thymus, possess, in addition to the CD4 marker, C D25 and Foxp3 markers (forkhead family transcription factor box p3), and suppress the immune response in a non-antigen-specific manner Naive T cells are converted to natural T reg cells by dendritic cells of the thymus under the influence of the cytokine thymi c stromal lymphopoietin (TSLP) Interestingly, among the richest sources ofTSLP are the cells of Hassa l l corpuscles of the thymus, which has been implicated in inducing nT reg cell formation (b) Inducible T reg cells (also known as T H3 cel ls) originate outside the thymus from naive T cells They inhibit the formation ofTH1 cells, thus suppressing the immune response (4) Natura l T killer cells are similar to NK cells except that they have to go to the thymus to become immunologically competent They are unusual in that they recognize lipid antigens that are presented t o them b y APCs i n conjunction with a CD molecule Natural T killer cells manufacture and secrete IL-4, IL- 0, and INF-y, and sport a limited range of TCRs on their plasma membranes I!1Jllt!llllij Lym phoid Tissue 207 C B lymphocytes Overview-B lymphocytes a B lymphocytes originate and mature into immunocompetent cells within the bone marrow They are responsible for the humoral immune response These cells go through a series of developmental steps going from pre-B cells through immature and finally transitional B cel ls, where they express different light and heavy chains of immunoglobulins on their cell membranes Transitional B cells travel to the spleen where they either die or undergo final maturation and become mature B cells b Mature B cells express immunoglobulins IgD and the monomeric form of IgM on the external aspect of their plasma membranes (known as surface immunog lobulins [slgs]); all of the immunoglobulin molecules on a particular B cell recognize and bind to the same a ntigenic determ inant (epitope) There are several types ofB cells, but B-2 B cells and B - B cells are the most predominant forms (1 ) B-2 B cells are the "conventional" B cells and will be referred to as "B cells" in this textbook; they are the most numerous and are present throughout the body; they must interact with T cells to propagate (in the bone marrow) and to become activated; they recognize an immense number of epitopes; and they are able to switch isotypes (i.e., switch in the synthesis of antibody types) and establish memory B cells They are considered to be firmly related to the adaptive immune system (2) B-1 B cells are much fewer in number than B cells and are usually limited to the gastrointestinal and respiratory systems; they very seldom require T-cell interaction; they not have to regenerate in the bone marrow but proliferate peripherally; they target carbohydrates rather than proteins; they very seldom switch isotypes; and they not establish memory B - B cells They cross over between the innate and adaptive immune systems c CD40 molecules are present on the plasmalemmae of B cells They interact with CD40 receptors on TH2 cells, causing release of cytokines that (1 ) facilitate proliferation and transformation of B cells into B memory and plasma cells and (2) inhibit TH cell proliferation d The specific cytokines that are released by T helper cells depend on the inva d i n g pathogen (1 ) IL-4 and IL-5 are released by T helper cells in response to parasitic worms causing B cells to switch to IgE formation (2) IL-6 and IFN-y are released by T helper cells in response to bacteria and viruses in the connective tissue, causing B cells to switch to IgG formation (3) Transforming growth factor � (TGF-�) is released by T helper cells in response to the presence of bacteria and viruses on mucosal surfaces causing B cells to switch to IgA formation e B lymphocytes can present epitopes complexed with class II human leukocyte antigen (HLA) to TH1 cells; therefore, they are considered to be APCs f When activated, B lymphocytes release I L-1 to induce TH1 cell formation and NK cell activation g During a humoral immune response to an antigenic challenge, B lymphocytes proliferate and differentiate to form plasma cells and B memory cells (Figure 12 1A) Plasma cells lack surface antibody and actively synthesize and secrete a ntibody specific against the challenging a ntigen B memory cells are long-lived committed immunocompetent cells that are formed during proliferation in response to an antigenic challenge They not react against the antigen but remain in the circulation or in specific regions of the lymphoid system Since they increase the size of the original clone, they provide a faster and g reater secondary response (anamnestic response) against a future challenge by the same antigen There are also two groups of B cells in the spleen: the more populous follicular B cells and fewer marginal zone B cells a Fol l icular B cells are more populous and are located in the primary and secondary follicles of the spleen (see VI C ofthis chapter); they sport IgM, IgD, and CD21 surface markers; and 208 BRS Cell B iology and H istology they are T cell dependent for immune function They are believed to be in the final stage of their maturation into fully functioning mature B cells b Marg i na l zone B cells are fewer in number than follicular B cells; are located in the marginal zone of the spleen (see VI C of this chapter); they sport IgM, CD 1, CD9, and CD21 on their plasmalemmae; they are T cell independent for their immune functions They react primarily to self-antigens and bacterial invasion CLI N I CAL CONSID ERATI O N S Common variable immunodeficiency is a d i s e a s e of the yo u n g , deve l o p i n g i n patie nts who a re b etwe e n a n d ye a rs o f a g e Alth o u g h th e s e p atie nts h ave n o rm a l B - c e l l p o p u l ati on, they d o n ot m a n ufacture e n o u g h i m m u n o g l o b u lins, with th e c o n s e q u e n c e of being p ro n e to re c u rrent res p i rato ry i nfecti o n s and the deve l o p m e nt of a uto i m m u n e d is o rd e rs such a s rh e u m ato id a rth ritis, thyro i d itis, and A d d i s o n disease Affe cted i n d ivid u a l s fre q u e ntly s uffe r from g a stroi ntesti n a l d i s o r d e rs, s u c h a s d i a rr h e a and i n s uffi c i e nt a b s o rpti o n of n utrie nts from th e a l i m e nta ry c a n a l Hodgkin disease is a m a l i g n a nt neoplastic transformation o f lymphocytes It o c c u rs m o stly in yo u n g m e n It is c h a cte rized by the prese n c e of Reed Sternberg cel ls, w h i c h a re g i a nt c e l l s with two l a rg e , va c u o lated n u c l ei, e a c h with a d e n s e n u c l e o l u s S i g n s a n d sym pto m s i n c l u d e p a i n less prog ressive enlargement o f t h e lymph nodes, spleen, and l iver; a n e m i a ; fever; wea kne ss; a n o rexi a ; and w e i g ht loss D NK cells belong to a category of null cel ls, a small group of peripheral-blood lymphocytes that lack the surface determinants that are characteristic of T and B lymphocytes However, they possess two specific receptors : killer activation receptors that respond to stress molecules and killer inhibition receptors that respond to MHC Class I molecules It is these receptors that aid them in the recognition of virally altered cells and tumor cells that have to be forced into apoptosis As soon as they are formed, NK cells are immunocompetent They not have to enter the thymic environment Not only are NK cells not MHC restricted but they also exhibit an apparently nonspecific cytotoxic ity against tumor cells and virus-infected cells The mechanism by which NK cells recognize these target cells is not yet understood NK cells can also kill specific target cells that have antibodies bound to their surface antigens in a process known as a ntibody-dependent cel l-med iated cytotoxicity (ADCC); macrophages, neutrophils, and eosinophils also exhibit ADCC NK cells use perforins and g ranzymes to drive the virally altered cells or tumor cells into apoptosis E Macrophages function both as APCs and as cytotoxic effector cells in ADCC When acting as APCs, macro phages phagocytose antigens, fragment them into small antigenic components, known as ep itopes, and present them to T cells Macrophages produce and release I L- , which helps activate TH cells and self- activate macrophages Moreover, they produce TN F-a, which also self-activates macrophages and induces the release of IL- 12; in conjunction with IFN-y facilitates killing of endocytosed bacteria (Table 12.2) In addition, macrophages secrete p rosta g l a n d i n E (PGE2 ), which decreases certain immune responses, I L-6, which activates T cells and stimulates B cells to differentiate into plasma cells, I L-12, which activates TH cells to proliferate and activates NK cells, I L-1 8, which acts on TH1 cells to produce IFN-y and also enhances NK cell activity, and I L-23, which decreases the motility of CDS + T cells It should be noted that I L-1, I L-6, and TN F-a act together t o induce a n inflammatory process I!1Jllt!llllij Lym phoid Tissue 209 A M H C The MHC (major histocompatibility complex) is a large genetic complex with many loci that encode two main classes of integral membrane molecules: class I molecules ( M H C ), which are expressed by nearly all nucleated cel ls, and class II molecules ( M H C II), which are expressed by the various cells that function as APCs In humans, the MHC is referred to as the H LA complex (human lymphocyte antigen) Therefore, MHC I is class I HLA, and MHC II is class II HLA As described below, MHC I molecules bind epitopes derived from endogenous protei ns, whereas MHC II molecules bind epitopes derived from exogenous proteins Both types of MHC molecules present their epitopes to T cells B lmmunogens are molecules that are capable of inducing an immune response All immunogens are antigens, that is, molecules whose epitopes can react with an anti body or a TCR (T cell receptor) Most, but not all, antigens are immunogens Exogenous immunogens are derived from proteins that were endocytosed or phagocytosed by APCs and degraded intracellularly, yielding antigenic peptides containing an epitope that enter the trans-Golgi network (TGN) I n the TGN, the complex is sorted into specialized antigenic peptides (containing a n epitope) that associate with class II H LA molecules (MHC II molecules) a These epitopes are relatively long, composed of 13 to 25 amino acids b Class II HLA molecules are synthesized on the rough endoplasmic reticulum (RER) and are loaded within the RER cisternae with a protein known as CLIP (class II-associated invariant protein) c The class II HLA-CLIP complex enters the Golgi apparatus, where it is delivered to MIIC vesicles (MHC class II compartment vesicles that already contain epitopes derived from exogenous immunogens), where the CLIP is exchanged for the epitope d The epitope-class II HLA complexes are transported to and displayed on the cell surface, where they are presented to T cells Endogenous immunogens are derived from proteins that were produced with i n host cells (these may be viral proteins synthesized in virus-infected cells or tumor proteins synthesized in cancerous cells) a Class I H LA molecules (MHC I molecules), synthesized on the RER surface, enter the RER cisternae b Endogenous immunogens are degraded by organelles of the host cells, known as proteasomes, into short polypeptide fragments These fragments are antigenic peptides (8- amino acids in length) known as ep itopes c The epitopes are transported by TAP1 and TAP2 (transporter proteins l and 2) into the RER cisternae d Within the RER cisternae, the epitopes derived from endogenous immunogens are loaded on the class I H LA e The peptide-class I HLA complexes are transported to the Golgi complex for sorting and eventual delivery within clathrin- coated vesicles to the cell surface, where they are presented to T cells C M H C ( H LA) restriction-T lymphocytes Each subtype of T lymphocytes (except T memory cells) recognizes only epitopes that are associated with either MHC I or MHC II (class I or class II HLA) molecules as follows: TH l and TH2 cells (CD4 + cells) recognize MHC II (class II HLA) molecules Cytotoxic T cells (CDS + cells) recognize MHC I (class I HLA) molecules T memory cells (CD45RO cells) recognize both MHC I and MHC II (class I and class II HLA) molecules 21 BRS Cell B iology and H istology Immunoglobulins are glycoproteins that are synthesized and secreted by p lasma cel ls They consti tute the active agents of the humoral immune response and have specific antibody activity against one antigen or a few closely related antigens Immunoglobulins bind antigens to form antigen antibody complexes, which are cleared from the body by various means, some of which involve the complement system, whereas others involve eosi nophi ls A Structure-Immunoglobu l i ns Immunoglobulins are composed of monomers containing two heavy chains and two light chains Each immunoglobulin possesses a constant reg ion that is identical in all immunoglobulin molecules of the same isotype Each immunoglobulin also possesses a variable reg ion that differs in the antibody molecules that recognize different antigens Thus, the variable reg ions determine the specificity of an antibody molecule (i.e., its ability to bind to a particular antigenic determinant) Large antigens may have multiple antigenic determinants, which induce production of antibodies with different specificities B Immunog lobulin classes (Table 12.3) Human serum contains five classes (isotypes) of immunoglobulins, which differ in the amino acid composition of their heavy-chain constant reg ions t a b I e 12.3 C lass Type of lg lgA S e c reto ry a ntibody lgD R e a g i n i c a ntibody lgE R e a g i n i c a ntibody lgG Serum immunoglobulin lgM Fi rst t o b e form e d in immune response I m m unoglobulin ( l g ) lsotypes a n d Their C h a cte ristics Cytokines Required for lsotype Switch Fraction of All lgs (%) and Ha lf-Life ( D ays) i n Serum TG F-� B i n d i n g to Cells Biological Characteristics 0- % d ays F o r m s te m p o ry atta c h m e nt to e p ith e l i a l c e l l s a s i t is bei n g s e c reted S e c reted as d i m e rs i nto s a l iva, tea rs, bile, l u m e n of g ut, a n d m i l k ( p rovi d i n g pa ssive i m m u n ity f o r i nfa nts); d i m e rs p rote cted by their s e c retory c o m p o n e nt l gA p rovides p rote ction a g a i nst patho g e n s a n d i nva d i n g a ntig ens 0.2% 3-8 d ays B-cell plasmalemma Allows B c e l l s t o re c o g n ize a ntig e n s a n d e l i c its a n i m m u n e response b y i n d u c i n g B - c e l l tra n sformation i nto p l a s m a c e l ls I L-4 and I L-5 M u c h less than % 2-5 d ays Plasmalemmae of m a st c e l l s a n d basophils Anti g e n i c b i n d i n g t o l g E l o c ated on m a st c e l l a n d b a s o p h i l p l a s m a m e m branes, i n d u c e s t h e s e c e l l s t o release th e i r p h a r m a c o l o g i c a l a g e nts i n d u c i n g a n i n sta nta n e o u s hyp ersensitivity response I F N -y, I L4, and I L-6 65-75% 23 d ays N e utro p h i l s and m a c ro p h a g e s lgG can p e n etrate the p l a c e ntal b a rrier, th ereby provi d i n g the fetus with passive i m m u n ity l g G binds to a ntig e n i c sites o n i nva d i n g path o g e ns, opsonizing them fa c i l itati n g p h a g o cytosis by m a c ro p h a g es a n d n e utro p h i l s lgG induces N K cells, thus i n itiati n g ADC C 8-1 0% 5-1 d ays lgM is a p e ntamer; however, its monomeric form b i n d s to B c e l l s Penta m e r i c l g M a ctivates the c o m p l e m e nt syste m The p r i n c i p a l p l a c e of form ation of l g M is the spleen IFN, interferon; IL i nterleukin; NK, natural killer; ADCC, antibody-dependent cel l-mediated cytotoxicity I!1Jllt!llllij Lym phoid Tissue 21 The different isotypes exhibit functional differences a lgA is secretory immunoglobulin that is released, in the form of dimers, into tears, bile, saliva, milk, and as part of the nasal discharge to protect the body (and the nursing infant) from p athogenic microorganisms and invading antigens It is protected from digestive enzymes by its secretory component synthesized by epithelial cells and hepatocytes b I g O and lgE are reaginic antibodies; IgE binds to IgE receptors of mast cells and basophils and prompts the release of pharmacologic agents from these cells to initiate an immediate hypersensitivity response IgD binds to B-cell plasma membranes and permits these cells to recognize antigens and thus initiate a response against antigenic challenges by prompting B cells to differentiate into antibody-secreting plasma cel ls c lgG , the most abundant serum immunoglobulin, crosses the placental barrier to shield the fetus-a process known as passive immun ity It attaches to antigenic sites on invading microorganisms, thus opsonizing these pathogens, making them available for phagocytosis by macrophages and neutrophils These antibodies activate NK cells, thus initiating ADCC d lgM forms pentamers and is the first isotype to be formed in an immune response It activates the complement system Its monomeric form binds to the B-cell plasma membrane Diffuse lymphoid tissue is considered to be a secondary lymphoid tissue It is especially prominent in the mucosae of the gastrointestinal and respiratory systems It is organized as nonencapsulated clusters of lymphoid cells or as lymphoid (lymphatic) nodules Diffuse lymphoid tissue is collectively called mucosa-associated lymphoid tissue (MALT) A MALT consists of two major types: bronchus-associated lymphoid tissue ( BALl) and g ut-associated lymphoid tissue (GALT) Both types possess lymphoid nodules that are isolated from one another, except in the case of Peyer patches B Peyer patches are aggregates of lymphoid nodules found in the i l eum They are components of the GALT C Lymphoid ( lymphatic) nodules are transitory dense spherical accumulations of lymphocytes (mostly B cells) The dark, peripheral region of nodules (corona) is composed mainly of small, newly formed lymphocytes Lymphoid nodules of the GALT are isolated from the lumina of their respective tracts by microfold (M) cel ls, which transfer antigens from the lumen and present them (without processing them into epitopes) to lymphocytes and macrophages lying in deep invaginations of their basal cell surfaces From here, an appropriate immune response is mounted by lymphoid tissue in the underlying lamina propria Secondary nodules, formed in response to an antigenic challenge, have a lightly staining central area called the germinal center, which is composed of B lymphocytes ( lymphoblasts [centroblasts] as well as centrocytes) A darker region, known as the mantle (corona), is composed of resting B cells that are being displaced from the germinal center by the newly formed B cells In addition to centroblasts and centrocytes, the germinal center houses B memory cells, plasma cells, migrating dendritic cells, follicular dendritic cells, macrophages, and reticular cells a Centroblasts not display surface immunoglobulins (sigs), whereas centrocytes have expressed sigs b Centrocytes that express sigs against self are forced into apoptosis c Surviving centrocytes become B memory cells or plasma cel ls d Migrating dendritic cel ls, derived from the bone marrow, are located in various regions of the body, and when they encounter an antigen, they travel to a nearby lymphoid nodule or lymph node to precipitate an immune reaction 21 BRS Cell B iology and H istology e Fol l icular dendritic cells are resident cells of lymph nodes or lymphoid nodules and challenge the slgs of newly formed centrocytes and force those centrocytes that not possess the proper slgs into apoptosis Macrophages phagocytose the remnants of apoptotic cells f Reticular cells are fibroblast-like cells that manufacture reticular fibers (type III collagen) to form the supporting skeleton of the lymphoid nodule and lymph node Primary nodules lack germinal centers and are composed of resting B memory cells, plasma cells, migrating dendritic cells, follicular dendritic cells, macro phages, and reticular cells A Lymph nodes Overview-Lymph nodes are secondary lymphoid organs a A lymph node is a small, ovoid to kidney-shaped structure with a capsule that sends trabeculae into the substance of the node (Figure 12.2) b The convex surface of a lymph node receives afferent lymphatic vessels, whereas the concave surface (the hilum) is the site where arterioles enter and venules and efferent lymphatic vessels exit c Lymph nodes possess a stroma composed of stromal cells and a supportive framework rich in reticular fibers FIGURE 2.2 This p h oto m i c ro g r a p h of a h u m a n lym p h node d e m o n strates that th e c a ps u l e (C) of th e node i s s u r ro u n d e d by a d i p ose ti s s u e (A) The c a p s u l e s e n d s tra b e c u l a e (T) i nto the s u b sta n c e ofthe n o d e N ote the pres e n c e of the s u b c a p s u l a r a n d p a ratra b e c u l a r s i n u s o i d s ( S ) a s w e l l a s th e g e rm i n a l c e nters ( G C ) o f the lym p h o i d n o d u l e s T h e p a c o rtex ( P C ) i s evi d e nt b etwe e n the c o rtex a n d the m e d u l l a ( X 32) I!1Jllt!llllij Lym phoid Tissue 213 d Function Lymph nodes filter lymph, maintain and produce T and B cells, and possess memory cells (especially T memory cells) Antigens delivered to lymph nodes by APCs are recognized by T cells, and an immune response is initiated Additionally, some of the stromal cells and some of the dendritic cells of lymph nodes express the transcription factor AIRE (auto immune regulator), which selectively induces anti-self-T cells that escaped destruction in the thymus to go into apoptosis Structure-Lymph nodes Lymph nodes are divided into three regions : the outermost cortex, the middle para cortex, and the innermost medulla (Figure 12.2) Stromal cells of these regions release a variety of chemotactic chemokines lymphocytes (CCLs) that attract lymphocytes Depending on the CCL released, B cells or T cells are attracted to a particular region of the lymph node In order to attract both B cells and T cells, CCLs are conveyed to the luminal endothelial cell membranes of postcapillary venules, the region where lymphocytes leave the circulatory system to enter the substance of the lymph node Once in the lymph node stroma, both B cells and T cells are segregated within the cortex of the lymph node by those CCLs to which each responds a The cortex of lymph nodes (1 ) lies deep to the capsule, from which it is separated by a subcapsular sinus (2) is incompletely subdivided into compartments by connective tissue septa derived from the capsule (3) contains lymphoid nodules and sinusoids (a) Lymphoid nodules are composed mainly ofB cells but also of some T cells, follicular dendritic cells, macrophages, and reticular cells They may possess a germinal center and then they are known as secondary lymphatic nodules (b) Sinusoids are endothelium-lined lymphatic spaces that extend along the capsule and trabeculae and are known as subcapsular and cortical sinusoids, respectively b The para cortex of the lymph node is located between the cortex and the medulla (1 ) It is composed of a non-nodular arrangement of mostly T lymphocytes (the thymus dependent area of the lymph node) and dendritic cells (2) The paracortex is the region where circulating lymphocytes gain access to lymph nodes via postcapillary (high endothelial) venules ( H EVs) c The medulla of a lymph node lies deep to the paracortex and cortex, except at the region of the hilum It is composed of medullary sinusoids and medullary cords (1 ) Medullary sinusoids are endothelium-lined spaces supported by reticular fibers and reticular cells They frequently contain macrophages and receive lymph from the cortical sinuses (2) Medullary cords are composed of lymphocytes and plasma cells B The thymus is a primary lymphoid organ Overview-Thymus a The thymus is a bilobed structure located in the neck It is derived from both endoderm (epithelial reticular cel ls), derived from the third pharyngeal pouch of the embryo, and mesoderm (lymphocytes [thymocytes]) The development of the epithelial reticular cells of the thymus (especially in the medulla) is dependent on the formation and release of lymphotoxi ns, members of the tumor necrosis factor family of cytokines In the absence of these proteins the thymus does not develop or function properly The thymus begins to involute near the time of puberty b A connective tissue capsule surrounds the thymus The septa of this capsule divide the parenchyma into incomplete lobules, each of which contains a cortical and medullary region (Figure 12.3) The thymus does not possess lymphoid nodules Structure-Thymus a The thymic cortex is supplied by arterioles in the septa; these arterioles provide capillary loops that enter the substance of the cortex The cortex is the region in which T-cell maturation occurs (1 ) Epithelial reticular cells (Figure 2.3) (a) There are six types of epithelial reticular cells (see Table 12.4) They are pale cells (derived, during embryogenesis, from the third and perhaps fourth pharyngeal pouches) and have a large ovoid lightly staining nucleus that often displays a nucleolus 21 BRS Cell B iology and H istology F I G U R E 2.3 T h i s l ow- power p h oto m i c ro g r a p h of the m o n key thym us d i s p l ays the dense c o rtex ( C ) and the l i g hter m e d u l l a ( M ) N ote the n u m e ro u s e p ith e l i a l reti c u l a r c e l l s ( a rrowheads) t h a t a r e q u ite evi d e nt i n the c o rtex a s well a s the thym i c ( H a s s a l l ) c o r p u s c l e s ( a rro w ) i n the m e d u l l a ( x 32) t a b I e 12.4 Reti c u l a r Epithelial Cells of th e Thym us Location Function J u n ction of the c a p s u l e and the c o rtex a s well a s surro u n d i n g the tra b e c u l a e that p a rti a l ly s e p a rates thym i c l o b u l e s f r o m e a c h oth e r Forms a b a rrier between the thym i c p a r e n c hyma and the rest of the bo dy; it a l s o assists in the formation of the bloo d-thym us b a rrier by surro u n d i n g blood vessels i n the thym i c c o rtex II Ste l l ate- s h a p e d c e l l s in t h e c o rtex where the processes of a d j a c e nt c e l l s form d e s m o s o m e s with e a c h oth e r The processes surro u n d a n d form c o m p a rtm e nts isolating m atu ri n g T cells They express MHC I and MHC II and se lf anti g e n m o l e c u l e s a n d p resent th e m to matu ring T c e l l s Ill O n the c o rti c a l a s p e ct of the c o rti c o m e d u l l a ry j u n ction T h e y f o r m the b o u n d a ry b etwe e n the c o rtex a n d the m e d u l l a They express M H C I a n d M H C I I a n d self-anti g e n m o l e c u l e s a n d p resent t h e m t o m atu ring T c e l l s IV O n the m e d u l l a ry a s p e ct of the c o rti c o m e d u l l a ry j u n ction T h e y a n d type I l l c e l l s isol ate the cortex fro m t h e m e d u l l a v Thro u g h o ut the m e d u l l a F o r m t h e cyto a r c h itectu ral fra mework of the m e d u l l a a n d form c o m p a rtme nts for T c e l l s VI Medulla F o r m H a s s a l l c o r p u s c les, which a re b e l ieved t o be res ponsible for d e l etion of T- c e l l c l o n e s that would recog nize a n d atta c k se lf p rote ins M a n ufa cture a n d release thym i c stro m a l lym p h o p o ietin that aids i n the formation of n atu ral T reg c e l l s Type Cortex Medulla I!1Jllt!llllij Lym phoid Tissue 21 (b) They possess long processes that surround the thymic cortex, isolating it from both the connective tissue septa and the medulla These processes, which are filled with bundles oftonofi laments, form desmosomal contacts with each other (c) They manufacture thymosin, serum thymic factor, thymopoietin, and thym ic stromal lymphopoietin, hormones that function in the transformation of immature T lymphocytes into immunocompetent T cells (2) Thymocytes (a) Thymocyte plasmalemma possesses Notch-1 receptors that permit these cells to respond to cytokines released by epithelial reticular cells to become T cells Once committed to the T-cell lineage, they are known as immature T lymphocytes and are noted to be present within the thymic cortex in different stages of differentiation (b) Thymocytes are surrounded by processes of epithelial reticular cells, which help segregate thymocytes from antigens during their maturation (c) They migrate toward the medulla as they mature Most T cells die in the cortex, and the dead cells are phagocytosed by macrophages (d) Surviving T cells are naive They leave the thymus and are distributed to secondary lymphoid organs by the vascular system (3) B lood-thymus barrier (a) This barrier exists in the cortex on ly, making it an immunologically protected region (b) It ensures that antigens escaping from the bloodstream not reach developing T cells in the thymic cortex (c) It consists of the following layers : endothelium of the thymic capillaries and the associated basal lamina, perivascular connective tissue and cells (e.g., pericytes and macrophages), and type I epithelial reticular cells and their basal laminae b Thymic medul l a (1 ) The thymic medulla i s continuous between adjacent lobules and contains large numbers of epithelial reticular cells and mature T cel ls, which are loosely packed, causing the medulla to stain lighter than the cortex (Figure 12.3) (2) It also contains whorl-like accretions of type VI epithelial reticular cells called Hassa ll corpuscles (thymic corpuscles) These structures display various stages of keratinization and increase in number with age It has been shown that these epithelial reticular cells manufacture TSLP (thymic stromal lymphopoietin), a cytokine that facilitates dendritic cell maturation which, in turn, elicit the transformation of naive T cells into natural T reg cells (3) Mature T cells exit the thymus via venules and efferent lymphatic vessels from the thymic medulla The T cells then migrate to secondary lymphoid structures (4) Hormones acting on the thymus (a) Thymosin, thymopoietin, thymulin (thymic factor), somatotropin, thymic stromal lymphopoietin, and thymic humoral factor promote the formation of immunocompetent T cells (b) Thyroxi n encourages thymulin production by epithelial reticular cells (c) Adrenocorticostero ids depress T-cell formation in the thymus CLI N I CAL CONSID ERATIO N S D i G eorge synd rome, a l s o c a l l e d congenita l thym ic aplasia, is c h a cte r ized by the c o n g e n ita l a b s e n c e of the thym us a n d p a rathyro i d g l a n ds, re s u lti n g from a b n o r m a l d eve l o p m e nt of the th ird and fo u rth p h a ryn g e a l p o u c h es This syn d ro m e is a s s o c i ated with abnormal cell-med iated immun ity b ut rel ative ly n o r m a l h u m o ral i m m u n ity It u s u a lly resu lts i n death fro m tetany or u n c o ntro l l a b l e infection C Spleen Overview-Spleen a A simple squamous epithelium (peritoneum) covers the dense irregular collagenous connective tissue capsu le of the spleen, which sends trabeculae into the substance of the spleen to form a supportive framework (Figure 12.4) 21 BRS Cell B iology and H istology F I G U R E 2.4 This l ow-p owe r p h oto m i c ro g r a p h d i s p l ays th e s m o oth c a p s u l e I C ) of a h u m a n s p l e e n O b s e rve that the spleen is n ot d ivi d e d i nto a c o rtex and a m e d u l l a ; i n ste a d , it h a s red pulp IRP) a n d wh ite p u l p N ote the p re s e n c e of a lym phoid n o d u l e with a g e rm i n a l c e nter IGC) c o m posed of B lym p h o cyte s The lym p h o i d n o d u l e i s invested by the T- c e l l-ri c h r e g i o n o f t h e s p l e e n , known a s the p e r i a rte r i a l lym p h ati c s h e ath I PALS ) T h e arrow p o i nts t o t h e m a r g i n a l z o n e l o c ated b etwe e n the white p u l p and the R P I X 32) b The spleen is similar to lymph nodes in that it possesses a hilum, but differs from both the thymus and the lymph nodes in that it lacks a cortex and medulla It further differs from lymph nodes because it has no afferent lymphatic vessels c The spleen is divided into red pulp and wh ite pulp; the latter contains lymphoid elements These two regions are separated from each other by the marginal zone (Figure 12.4) d Function-Spleen The spleen filters blood, phagocytoses damaged and aged erythrocytes, and is a site of proliferation of B and T lymphocytes and the production of antibodies by plasma cells In some animals, such as the dog but not in humans, it stores red blood cells Vascularization of the spleen is derived from the splenic artery, which enters the hilum and gives rise to trabecular arteries a Trabecular a rteries leave the trabeculae, become invested by a periarterial lymphatic sheath (PALS, described later), and are known as central arteries b Centra l arteries branch but maintain their lymphatic sheath until they leave the white pulp to form several straight penicillar arteries c Pen icillar arteries enter the red pulp They have three regions : pulp arterioles, macrophage sheathed arterioles, and terminal arterial capillaries These last named vessels either drain directly into the splenic sinusoids (closed circu lation) or terminate as open-ended vessels within the splenic cords of the red pulp (open circulation) d Splenic sinusoids are drained by pulp veins, which are tributaries of the trabecular veins; these in turn drain into the splenic vein, which exits the spleen at the hilum Structure-Spleen a Wh ite pulp of the spleen includes all of the organ's lymphoid tissue (diffuse and nodular), such as lymphoid nodules (mostly B cells) and PALS (mostly T cells) around the central arteries It also contains macro phages and other APCs I!1Jllt!llllij Lym phoid Tissue 21 b The marginal zone (MZ) of the spleen (1 ) is a sinusoidal region between the red and white pulps at the periphery of the PALS (Figure 2.4) (2) receives blood from capillary loops derived from the central artery and is thus the fi rst site where blood contacts the splenic parenchyma (3) is richly supplied by avidly phagocytic macrophages and other APCs There are two types of macrophages in the marginal zone: the MZ macrophages and the MZ metallophilic macrophages (a) MZ macrophages express molecules on their surface that recognize pathogens such as bacteria, viruses, and yeasts (b) MZ metallophilic macrophages express molecules that bind to cell-bound oligosaccharide ligands; these macrophages also interact with marginal zone B cells (see Section II C b in this chapter), promoting them to migrate to the white pulp of the spleen and present blood-borne antigens to T cells (4) The MZ is the region where circulating T and B lymphocytes enter the spleen before becoming segregated to their specific locations within the organ and where interd ig itati ng dendritic cells are able to display their MHC-epitope complex for recognition by T cells (5) Stromal cells of the MZ release a variety ofCCLs (chemotactic chemokines lymphocytes) that attract lymphocytes D epending on the CCL released, B cells or T cells are attracted to a particular region of the spleen In order to attract both B cells and T cells to the MZ, CCLs are conveyed to the luminal endothelial cell membranes of MZ sinusoids Once in the spleen parenchyma, both B cells and T cells are segregated within the white pulp of the spleen by those CCLs to which each responds c Red pulp of the spleen (Figure 12.4) is composed of an interconnected network of sinusoids supported by a loose type of reticular tissue (splenic cords) (1 ) Sinusoids (a) are lined by long fusiform endothelial cells separated by relatively large blood containing intercellular spaces (b) have a discontinuous basal lamina underlying the endothelium and circumferen tially arranged ribs of reticular fibrils (2) Splenic cords (cords of B i l l roth ) contain plasma cells, stellate reticular cells, blood cells, and macro phages enmeshed within the spaces of the reticular fiber network Processes of the macrophages enter the lumina of the sinusoids through the spaces between the endothelial cells D Tonsils are aggregates of lymphoid tissue, which sometimes lack a capsule All tonsils are in the upper section of the digestive tract, lying beneath but in contact with the epithelium B and T cells in the three sets of tonsils are localized in different regions of any particular tonsil The mechanism of distribution is similar to that which occurs in lymph nodes and the spleen, and depends on the various chemotactic chemokines for lymphocytes (CCLs) secreted by stromal cells Tonsils assist in combating antigens entering via the nasal and oral epithelia Palatine tonsils a possess crypts, deep invaginations of the stratified squamous epithelium covering of the tonsils, frequently containing debris; b possess primary and secondary (with germinal centers) lymphoid nodules; c are separated from subjacent structures by a connective tissue capsu le The pharyngeal tonsil is a single tonsil in the posterior wall of the nasopharynx a It is covered by a pseudostratified ciliated columnar epithelium b Instead of crypts, it has longitudinal pleats (infoldings) c Possesses primary and secondary (with germinal centers) lymphoid nodules Li ngual tonsil a is on the dorsum of the posterior third of the tongue and is covered by a stratified squamous nonkeratinized epithelium b possesses deep crypts, which frequently contain debris Ducts of the posterior mucous glands of the tongue often open into the base of these crypts c possesses primary and secondary (with germinal centers) lymphoid nodules Review Test D i rections: Each of the numbered items or incomplete statements in this section is followed by answers or completions of the statement Select the ONE lettered answer that is BEST in each case Which of the following statements concern ing T helper cells is true? (A) They possess membrane-bound antibodies (B) They can recognize and interact with antigens in the blood (C) They produce numerous cytokines (D) They function only in cell-mediated immunity (E) Their activation depends on interferon-y Which of the following statements concern A patient who was given penicillin had an adverse reaction to the antibiotic Although the reaction was due to the actions of mast cells, the response occurred because mast cells have IgE receptors in their cell membranes Which of the following cells produced the IgE decorating the plasma cell's surface? (A) (B) (C) (D) (E) T memory cells B memory cells T helper cells Plasma cells T cytotoxic cells ing T cytotoxic (Tc) cells is true? (A) They assist macro phages in killing (B) (C) (D) (E) microorganisms They possess antibodies on their surfaces They possess CD8 surface markers They possess CD28 surface markers They secrete interferon-y Which of the following cell types is thought to function in suppressing the immune response? (A) (B) (C) (D) (E) Inducible T reg cells B cells T memory cells TH cells Mast cells Which of the following statements concerning the thymus is true? (A) Lymphoid nodules form much of the thymic cortex ( B ) Epithelial reticular cells form Hassall corpuscles (C) T cells migrate into the medulla, where they become immunologically competent ( D ) Most T cells that enter the thymus are killed in the medulla (E) Macrophages are essential components of the blood-thymus barrier Which of the following statements concerning Hassan corpuscles is true? Which of the following statements concern ing interferon-y is true? (A) They are located in the thymic cortex of (A) (B) (C) (D) (E) ( B ) They are located in the thymic cortex of old 21 It is produced by T memory cells It is produced by T reg cells It activates macrophages It inhibits macrophages It induces viral proliferation young individuals individuals (C) They are derived from mesoderm ( D ) They are located in the thymic medulla (E) They are derived from T memory cells I!1Jllt!llllij Lym phoid Tissue 21 After their maturation in the thymus and release into the circulation, T lymphocytes migrate preferentially to which of the following sites? Which of the following statements about IgG is true? (A) (B) (C) (D) (E) (B) (C) (D) (E) Para cortex of lymph nodes Cortical lymphoid nodules of lymph nodes Hilum of lymph nodes Lymphoid nodules of the tonsils Lymphoid nodules of the spleen In which of the following sites lympho cytes become immunocompetent? (A) Germinal center of secondary lymphoid (B) (C) (D) (E) nodules White pulp of the spleen Thymic cortex Red pulp of the spleen Paracortex of lymph nodes (A) It is located in the serum and on the membrane of B cells It can cross the placental barrier It is involved in allergic reactions It exists as a pentamer It binds to antigens on the body surface and in the lumen of the gastrointestinal tract Answers and Explanations C T helper cells produce a number of cytokines that affect other cells involved in both the cell mediated and humoral immune responses T helper cells possess antigen-specific TCRs (not antibodies) on their membranes These cells recognize and interact with antigenic determi nants that are associated with class II HLA molecules on the surface of APCs IL- l is necessary for activation of T helper cells (see Chapter 12 II B c) C T cytotoxic cells are CDS + cells CD28 molecules are present on TH l cells IFN-y is released by THl cells, which also assist macrophages in killing microorganisms (see Chapter 12 II B c) A The immune response is decreased by inducible T reg cells They suppress the formation of TH l cells, thereby suppressing the immune response (see Chapter 12 II B c) C Interferon-y activates macrophages, NK cells, and T cytotoxic cells, enhancing their phagocytic or cytotoxic activity or both (see Chapter 12 II E 2) D Individuals allergic to penicillin produce IgE antibodies The cells that manufacture IgE are plasma cells After an antigenic challenge, proliferation and differentiation of B cells give rise to plasma cells and B memory cells (see Chapter 12 II C 2) B Epithelial reticular cells of the medulla congregate to form Hassan (thymic) corpuscles (see Chapter 12 VI B b) D Hassall corpuscles are concentric accretions of epithelial reticular cells (derived from endoderm) found only in the medulla of the thymus (see Chapter 12 VI B b) A T lymphocytes are preferentially located in the paracortex of lymph nodes, whereas B lymphocytes are found in lymphoid nodules located in lymph nodes, tonsils, and the spleen (see Chapter VI A a) C T lymphocytes mature and become immunocompetent in the cortex of the thymus, whereas B lymphocytes so in the bone marrow After an antigenic challenge, lymphocytes proliferate and differentiate in various lymphoid tissues (see Chapter 12 II B and II C ) B IgG is the most abundant immunoglobulin isotype i n the serum I t can cross the placental barrier but does not bind to the B-cell plasma membrane It exists as a monomer, functions to activate complement, and acts as an opsonin (see Chapter 12 IV B 2) 220 ... II Ill IV 61 40 13 9 Contents NERVOUS SYSTEM I II Ill IV v VI VII VIII IX X XI Overview-Nervous System 14 3 14 3 14 5 Cells o f Nervous System 15 1 Synapses Nerve Fibers 15 2 15 3 Ganglia 15 5 Histophysiology... Growth Factors ( CSFS ) 17 9 Review Test 18 1 11 I II Overview-Blood Vascular System 18 4 Overview-Lymphatic Vascular System Review Test 12 18 4 CIRCULATORY SYSTEM 19 5 19 6 19 9 LYMPHOID TISSUE I II... System Cells of the Immune System 19 9 2 01 Antigen Presentation and the Role of MHC Molecules Immunoglobulins 210 Diffuse Lymphoid Tissue Lymphoid Organs Review Test 218 212 211 209 viii 13 Contents