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CHAPTER 21: THE LYMPHATIC SYSTEM AND IMMUNITY Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Introduction Immunity Innate (nonspecific) immunity Ability to ward off damage or disease Susceptibility is lack of resistance Defenses that are present at birth Provide rapid re...
CHAPTER 21: THE LYMPHATIC SYSTEM AND IMMUNITY Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Introduction Immunity Innate (nonspecific) immunity Ability to ward off damage or disease Susceptibility is lack of resistance Defenses that are present at birth Provide rapid response to all types of disease Adaptive (specific) immunity Develops in response to contact with specific pathogen (disease-producing microbes) Occurs more slowly, but has memory: responds faster and stronger to specific pathogens after initial exposure Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymphatic System Consists of Lymph Lymphatic vessels Lymphatic tissues Specialized reticular connective tissue with large numbers of B and T lymphocytes Red bone marrow Functions Drains excess interstitial fluid and returns proteins to bloodstream Transports dietary lipids Carries out immune responses Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymphatic System Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymph Capillaries and Vessels Lymphatic capillaries Lacteals Begin closed-ended in tissue spaces between cells Unique one-way structure permits interstitial flow into but not out of vessels Specialized in small intestine to absorb dietary lipids Lymph vessels have valves like vein Form from merged lymph capillaries Convey lymph into and out of lymph nodes Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymph Capillaries and Vessels Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymph Trunks and Ducts Lymphatic trunks Right lymphatic duct Lymphatic vessels in particular region of body from cluster of nodes unite to form trunks Flow into one of two ducts Receives lymph from right head, neck and chest Thoracic duct Main duct, begins as cisterna chyli dilation in abdomen Receives lymph from left head, neck and chest, abdomen, pelvis and distal limbs Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymph Trunks and Ducts Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymph Trunks and Ducts Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Formation and Flow of Lymph Lymph forms from excess interstitial fluid Flow of lymph by same mechanisms that return venous blood to heart Filtered from blood capillaries, with only small amount of proteins Skeletal muscle pump (“milking” action) Respiratory pump (inhalation pressure changes) Sequence of fluid flow: blood capillaries – interstitial fluid – lymph capillaries, vessels, nodes, trunks and ducts – venous blood near junction of internal jugular and subclavian veins Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Formation and Flow of Lymph Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Animation Lymph Formation and Flow You must be connected to the internet to run this animation. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymphatic Organs and Tissues Primary lymphatic organs and tissues are site of stem cell division and development of immunocompetent B and T lymphocytes Red bone marrow Thymus Secondary lymphatic organs and tissues are site of most immune responses Lymph nodes Spleen Lymphatic follicles Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Primary Lymphatic Organs and Tissues Red bone marrow In flat bones and proximal epiphyses of the proximal long bones in adults Stem cells produce both B and T lymphocytes B cells mature here Thymus Bilobed organ with connective tissue capsule that atrophies as we age Immature T cells migrate to thymus to multiply and mature Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Primary Lymphatic Organs and Tissues Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Secondary Lymphatic Organs and Tissues Lymph nodes Located along lymphatic vessels Many afferent vessels enter One efferent vessel leaves at hilum (depression) Encapsulated Function as a type of filter for foreign substances Sufficient time for response because reticular fibers trap and lymph outflow is slow Macrophages destroy by phagocytosis Lymphocytes destroy by immune responses Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymph Nodes Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Lymph Nodes Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Secondary Lymphatic Organs and Tissues Spleen Largest mass of lymphatic tissue Filters blood White pulp – site of B and T cell immune response and macrophage destruction of pathogens Red pulp – removal of worn-out or defective blood cells and platelets, platelet storage, and hemopoiesis during fetal life Mucosa associated lymphatic tissue (MALT) Concentrations of lymphatic tissue without capsule scattered throughout tracts of several organs Include large aggregation of appendix, tonsils, Peyer’s Patches Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Spleen Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Tonsils Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific) Acts against all microbes in the same way First line of defense Skin – closely packed keratinized epithelial cells Mucous membranes – mucus traps and cilia sweep microbe away Chemicals and fluids – tears, saliva, urine, vaginal secretions, sebum, perspiration Defecation and vomiting – expel microbes Lysozyme – enzyme destroys Acidity – discourages bacterial growth Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Animation Introduction to Disease Resistance You must be connected to the internet to run this animation. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific) Second line of defense - internal Natural killer cells Phagocytes – perform phagocytosis Inflammation – sequence of steps with four key signs and symptoms Fever Attack any body cells that display abnormal cell membrane proteins, causing target cell to undergo apoptosis Release perforin and granzymes Hypothalamus sets abnormally high systemic temperature Inhibits microbe growth and intensifies effect of interferons Antimicrobial proteins – interferon and complement system Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific): Phagocytosis Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific): Inflammation Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific) Two major types of phagocytes Neutrophils Blood phagocytes First line Most abundant WBC Small, short-lived Macrophages Monocytes migrate to infected tissue and become either wandering or fixed macrophages in the tissues Second line Larger, longer-lasting Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific) Inflammation at site of injury aids in disposal of foreign substance and prepares for tissue repair Four characteristic signs and symptoms Three basic activities Redness, localized heat, swelling, and pain Vasodilation of local blood vessels Increased permeability of local blood vessels Emigration of phagocytes (diapedesis): chemotaxis and microbial attack Major Inflammatory Chemicals Histamine, prostaglandins, and bradykinins Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific) Antimicrobial interferon Proteins produced by virus-infected cells Block viral replication in neighboring unaffected cells Complement system Group of normally inactive proteins in blood plasma and on plasma membranes enhance certain immune reactions Help clear antigens from body once activated by cascade of reactions by sequence of opsonization, cytolysis, formation of membrane attack complex, and stimulation of inflammation and chemotaxis of phagocytes Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific) Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Innate Immunity (Nonspecific) Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Animation Non-Specific Disease Resistance You must be connected to the internet to run this animation. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Adaptive Immunity (Specific) Body’s defense activities against each particular antigen Antigens are substances recognized as foreign, that produce an immune response Microbes, foreign tissues and pollen are recognized Distinction from innate immunity Specificity for particular foreign antigen, distinguished as nonself from self molecules on cells Memory for previously encountered antigens, so second exposure prompts more rapid and vigorous response Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Adaptive Immunity (Specific) Maturation of B and T cells Both lymphocytes arise from stem cells in red bone marrow B cells complete development in red bone marrow Immature T cells migrate to thymus to mature Immunocompetence Ability to recognize and react to a specific antigen During maturation, cells make and insert several distinct proteins in their cell membranes that function as specific antigen receptors T cells also insert other surface protein to facilitate coupling with antigen-presenting cell Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Adaptive Immunity (Specific) Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Types of Adaptive Immunity Cell-mediated immunity Antibody-mediated immunity Cytotoxic T cells directly attack invading antigens Effective against pathogens, cancer cells, and transplant tissues Activated B cells transform into plasma cells Plasma cells synthesize and secrete specific antibody to bind with specific antigen Mainly effective against extracellular pathogens, including viruses, bacteria, and fungi Both responses typically active when foreign substance invades with multiple copies of antigen Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Adaptive Immunity Clonal selection Process by which a lymphocyte divides and differentiates into a clone of cells that can recognize the same specific antigen as original activated cell Two major types of cells from clone Effector cells – carry out immune response to destroy or inactivate antigen-bearing substance Memory cells – don’t participate in current immune response and have a long life span; will divide and differentiate into more effector and memory cells if same antigen is encountered in future Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Antigen and Major Histocompatibility Complex Antigens (MHCs) Molecules Typically large complex molecules, often proteins Epitope – small part of antigen that is recognized as foreign and triggers an immune response Structures, toxins and nonmicrobial antigens can also trigger immune response Major histocompatibility complex (MHC) Cell surface “self-antigens” on all body cells Help T cells distinguish own body cells from foreign cells for adaptive immunity Autoimmune disorders occur when the immune system attacks its own cells Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Processing and Presentation of Antigens Antigen-presenting cells (APCs) Special class of cells that process and present exogenous antigens (i.e. foreign) Include dendritic cells, macrophages, and B cells Strategically located where antigens likely to penetrate innate defenses After processing, migrate to lymphatic tissue to present antigen to T cells and trigger immune response Sequence of processing exogenous antigen Phagocytosis and digestion of antigen into peptide fragments that are associated with MHC and inserted into cell membrane Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Processing and Presentation of Antigens Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Processing and Presentation of Antigens Processing of endogenous antigens Infected cell has antigens inside cell Include viral proteins, bacterial toxins, abnormal proteins synthesized by cancerous cell Fragments of antigen bind to MHC and are inserted into cell membrane Signals as an infected cell for immune response Cytokines Small hormones that simulate or inhibit many normal cell functions, such as growth and differentiation, such as interferon and interleukin Secreted by lymphocytes and APCs for immune response Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Cell-Mediated Immune Begins with activation of a small number of T Response cells by specific antigen First, helper T cell receptor binds to antigen fragments associated with MHC molecules Costimulation by cytokines is also required for activation Activated T cell undergoes clonal selection into active and memory T cells Two kinds of T cells with different coupling proteins for antigen-MHC complex Helper T cells with CD4 Cytotoxic T cells with CD8 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Helper T Cells and APCs Inactive helper T cells recognize MHC-antigen complex on antigen presenting cell and binds with CD4 protein If costimulation occurs, activated helper T cell undergoes clonal selection into active and memory helper T cells Active helper T cells respond within hours of costimulation by secreting cytokines Acts as a costimulator for other T cells, and enhances proliferation of B cells and natural killer cells Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Helper T Cells and APCs Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Cytotoxic T Cells and Body Cells Inactive cytotoxic T cells recognizes MHC-antigen complex on infected or abnormal body cell and binds with CD8 protein If costimulation occurs, activated cytotoxic T cell undergoes clonal selection into active and memory cytotoxic T cells Active cytotoxic T cells leave lymphatic tissue and secrete various substances to kill infected target body cells (only ones with the specific antigen) Granzymes – trigger apoptosis of target cell Perforin – cell membrane cytolysis of target cell Granulysin – destroys intracellular microbes Lymphotoxin – fragments target cell DNA Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Cytotoxic T Cells and Body Cells Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Cytotoxic T Cells and Body Cells Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Animation Cell-Mediated Immunity You must be connected to the internet to run this animation. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Antibody-Mediated Immune Response Begins with activation of B cells by specific antigen B cells can respond to unprocessed antigens Costimulation by Helper T cell cytokine after forming antigen-MHC complex in own cell membrane produces more intense response Activated B cell undergoes clonal selection into plasma cells and memory B cells Plasma cells secrete antibody specific to antigen 5 classes of antibodies based on chemistry and structure, each with own biological role Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. AntibodyMediated Immune Response Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Antibodies Globulin plasma glycoprotein - immunoglobulin Form antigen-antibody complex with specific complementary antigen epitope that triggered its synthesis and secretion by plasma cells Disables antigen for destruction by other actions 5 classes of antibodies based on chemistry and structure, each with specific biological roles IgG IgA IgM IgD IgE Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Antibody Actions Neutralize antigen Immobilize bacteria Connect antigen-bearing pathogens to each facilitating phagocytosis Activate complement system plasma proteins Limits their spread to nearby tissues Agglutinate and precipitate antigen Blocking attachment of antigen to body cells Cascade of nonspecific reactions to destroy this specific antigen-bearing substance Enhance phagocytosis Attract phagocytes to antigen-antibody complex Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Antibodies Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Animation Antibody-Mediated Immunity You must be connected to the internet to run this animation. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Adaptive Immunity Response Cells Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Immunological Memory Primary response Immune response triggered by first exposure to specific antigen Slow rise in antibody levels (IgM and IgG) in blood several days after exposure, followed by gradual decline Involves activation of B and T cells for immune response and clonal selection of memory B and T cells Secondary response Subsequent exposure to same antigen triggers greater antibody level (mainly IgG) in blood from activation of memory cells Basis for immunization by vaccination to trigger memory cell clonal selection to antigen without causing illness Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Immunological Memory Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Immunological Memory Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. End of Chapter 21 Copyright 2015 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of these programs or from the use of the information herein. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.