Lymph Transport and Immunity

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1 Lymph Transport and Immunity Outline The Lymphatic System Lymph Vessels Lymphoid Organs Nonspecific Defenses Barriers Inflammatory Response Specific Defenses Antibodies T Cells Induced Immunity Active versus Passive Immunity Immunity Side Effects Allergies Blood Typing 2 國立交通大學生物科技學系陳文亮老師 1

2 The Lymphatic System Consists of lymphatic vessels and the lymphoid organs Three main homeostatic functions: Lymphatic capillaries take up and return excess fluid to the bloodstream Lacteals receive lipoproteins and transport them to the bloodstream Helps defend body against disease 3 Lymphatic System 4 國立交通大學生物科技學系陳文亮老師 2

3 The Lymphatic Organs 5 Lymphatic System One-way system that begins with lymphatic capillaries Take up fluid that has been diffused from, and not reabsorbed by, blood capillaries Edema - Localized swelling due to accumulation of tissue fluid Lymph flows one way From a capillary to ever-larger lymphatic vessels Finally to a lymphatic duct, which enters a subclavian vein 6 國立交通大學生物科技學系陳文亮老師 3

4 Lymphoid Organs Lymph Nodes - Capsule surrounding two distinct regions, cortex and medulla Lymphocytes congregate in cortex when fighting off a pathogen Macrophages concentrated in medulla - cleanse lymph Lymph nodes named for their location 7 Tonsils Lymphoid Organs Patches of lymphatic tissue located around the pharynx First to encounter pathogens that enter via the nose and mouth Spleen Located in upper left region of abdominal cavity just beneath diaphragm Cleanses blood 8 國立交通大學生物科技學系陳文亮老師 4

5 Thymus Gland Lymphoid Organs Located along trachea behind the sternum in upper thoracic cavity Produces thymic hormones Red Bone Marrow Origin for all types of blood cells Area of maturation for most white blood cells 9 Immune System Nonspecific Defenses Barriers to entry serve as mechanical barriers Skin Mucous membranes lining respiratory, digestive, and urinary tracts 10 國立交通大學生物科技學系陳文亮老師 5

6 Nonspecific Defenses Inflammatory Reaction Damaged cells and mast cells release histamine and kinins Capillaries dilate and become more permeable Enlarged capillaries cause skin to redden Swollen area and kinins stimulate free nerve endings causing pain 11 Inflammatory Reaction Neutrophils and monocytes migrate to the site of injury Neutrophils and mast cells phagocytize pathogens Monocytes differentiate into macrophages 12 國立交通大學生物科技學系陳文亮老師 6

7 Inflammatory Response 13 Complement System A collection of plasma proteins Activated when pathogens enter the body Complements certain immune responses Interferon binds to receptors of noninfected cells Causes them to prepare for possible attack Produce substances that interfere with viral replication 14 國立交通大學生物科技學系陳文亮老師 7

8 Action of the Complement System Against a bacterium 15 Specific Defenses An antigen is any foreign substance that stimulates the immune system to react Lymphocytes capable of recognizing antigens Have antigen receptors on plasma membrane Protein s shape allow it to combine with a specific antigen 16 國立交通大學生物科技學系陳文亮老師 8

9 Specific Defenses Immunity primarily the result of B lymphocytes B cells give rise to plasma cells Produce antibodies T lymphocytes T cells directly attack cells that bear non-self proteins 17 T Cells Requirements for T cell antigen recognition: Antigen must be presented by an antigenpresenting cell Antigen is first linked to a major histocompatibility complex (MHC) protein in the plasma membrane Cytokines - signaling chemicals that stimulate various immune cells 18 國立交通大學生物科技學系陳文亮老師 9

10 Cytotoxic T Cells Types of T Cells Destroy antigen-bearing cells Contain Perforins Helper T Cells Regulate immunity by secreting cytokines 19 Humoral (antibody-mediated) immune response Antigen (1st exposure) Engulfed by Cell-mediated immune response Key Stimulates Gives rise to Antigenpresenting cell B cell Helper T cell Cytotoxic T cell Memory Helper T cells Plasma cells Memory B cells Antigen (2nd exposure) Memory Cytotoxic T cells Active Cytotoxic T cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells. 20 國立交通大學生物科技學系陳文亮老師 10

11 Key Humoral (antibody-mediated) immune response Stimulates Gives rise to Antigen (1st exposure) Engulfed by Antigenpresenting cell B cell Helper T cell Memory Helper T cells Plasma cells Memory B cells Antigen (2nd exposure) Secreted antibodies Defend against extracellular pathogens 21 Cell-mediated immune response Antigen (1st exposure) Engulfed by Antigenpresenting cell Key Stimulates Gives rise to Helper T cell Cytotoxic T cell Memory Helper T cells Antigen (2nd exposure) Memory Cytotoxic T cells Active Cytotoxic T cells Defend against intracellular pathogens 22 國立交通大學生物科技學系陳文亮老師 11

12 Helper T Cells: A Response to Nearly All Antigens A surface protein called CD4 binds the class II MHC molecule This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs Activated helper T cells secrete cytokines that stimulate other lymphocytes 23 Antigenpresenting cell Bacterium Peptide antigen Humoral immunity (secretion of antibodies by plasma cells) Cytokines B cell Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Cytotoxic T cell Cell-mediated immunity (attack on infected cells) 24 國立交通大學生物科技學系陳文亮老師 12

13 Cytotoxic T Cells: A Response to Infected Cells Cytotoxic T cells are the effector cells in cellmediated immune response Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell BindingtoaclassIMHCcomplexonaninfected cell activates a cytotoxic T cell and makes it an active killer The activated cytotoxic T cell secretes proteins that destroy the infected target cell 25 Cytotoxic T cell Perforin Granzymes CD8 Class I MHC molecule TCR Target cell Peptide antigen 26 國立交通大學生物科技學系陳文亮老師 13

14 Cytotoxic T cell CD8 Class I MHC molecule TCR Perforin Granzymes Pore Target cell Peptide antigen 27 Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 Class I MHC molecule TCR Pore Dying target cell Target cell Peptide antigen 28 國立交通大學生物科技學系陳文亮老師 14

15 Cell-mediated Immunity 29 B Cells: A Response to Extracellular Pathogens The humoral response is characterized by secretion of antibodies by B cells Activation of B cells is aided by cytokines and antigen binding to helper T cells Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity 30 國立交通大學生物科技學系陳文亮老師 15

16 Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule TCR CD4 Helper T cell Activated helper T cell Cytokines Clone of plasma cells Clone of memory B cells Endoplasmic reticulum of plasma cell Secreted antibody molecules 2 µm 31 Antigen-presenting cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell 32 國立交通大學生物科技學系陳文亮老師 16

17 Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule TCR CD4 Cytokines Helper T cell Activated helper T cell 33 Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule TCR CD4 Clone of plasma cells Secreted Cytokines antibody molecules Helper T cell Activated helper T cell Clone of memory B cells 34 國立交通大學生物科技學系陳文亮老師 17

18 Fig Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells 35 Endoplasmic reticulum of plasma cell 2 µm 36 國立交通大學生物科技學系陳文亮老師 18

19 How many antibody classes do have we? Antibody Classes The five major classes of antibodies, or immunoglobulins, differ in distribution and function Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen Monoclonal antibodies are prepared from a single clone of B cells grown in culture 38 國立交通大學生物科技學系陳文亮老師 19

20 Immunoglobins IgG - Main antibody type in circulation IgM - Found in circulation Largest antibody IgA - Found in secretions IgD - Found on surface of immature B cells IgE - Found as antigen receptors on basophils in blood and on mast cells in tissue 39 Fig Class of Immunoglobulin (Antibody) Distribution Function IgM (pentamer) J chain First Ig class Promotes neutralization and cross- produced after initial exposure to linking of antigens; antigen; then its very effective in concentration in complement system the blood declines activation IgG (monomer) Most abundant Ig class in blood; also present in tissue fluids Promotes opsonization, neutralization, and cross-linking of antigens; less effective in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus IgA (dimer) J chain Present in secretions such as tears, saliva, mucus, and breast milk Provides localized defense of mucous membranes by cross-linking and neutralization of antigens Secretory component Presence in breast milk confers passive immunity on nursing infant IgE (monomer) Present in blood at low concentrations Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions IgD (monomer) Transmembrane region Present primarily on surface of B cells that have not been exposed to antigens Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) 40 國立交通大學生物科技學系陳文亮老師 20

21 41 Fig a Class of Immunoglobulin (Antibody) Distribution Function IgM (pentamer) J chain First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutralization and crosslinking of antigens; very effective in complement system activation 42 國立交通大學生物科技學系陳文亮老師 21

22 43 Fig b Class of Immunoglobulin (Antibody) Distribution Function IgG (monomer) Most abundant Ig class in blood; also present in tissue fluids Promotes opsonization, neutralization, and cross-linking of antigens; less effective in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus 44 國立交通大學生物科技學系陳文亮老師 22

23 45 The Role of Antibodies in Immunity Neutralization occurs when a pathogen can no longer infect a host because it is bound to an antibody Opsonization occurs when antibodies bound to antigens increase phagocytosis Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis 46 國立交通大學生物科技學系陳文亮老師 23

24 Viral neutralization Virus Opsonization Bacterium Macrophage Activation of complement system and pore formation Complement proteins Formation of membrane attack complex Flow of water and ions Pore Foreign cell 47 Fig c Class of Immunoglobulin (Antibody) IgA (dimer) J chain Distribution Present in secretions such as tears, saliva, mucus, and breast milk Function Provides localized defense of mucous membranes by cross-linking and neutralization of antigens Secretory component Presence in breast milk confers passive immunity on nursing infant 48 國立交通大學生物科技學系陳文亮老師 24

25 49 50 國立交通大學生物科技學系陳文亮老師 25

26 51 Fig d Class of Immunoglobulin (Antibody) IgE (monomer) Distribution Present in blood at low concentrations Function Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions 52 國立交通大學生物科技學系陳文亮老師 26

27 53 54 國立交通大學生物科技學系陳文亮老師 27

28 Fig e Class of Immunoglobulin (Antibody) Distribution Function IgD (monomer) Transmembrane region Present primarily on surface of B cells that have not been exposed to antigens Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) 國立交通大學生物科技學系陳文亮老師 28

29 57 58 國立交通大學生物科技學系陳文亮老師 29

30 Antibody-Mediated Immunity Clonal selection theory: The antigen selects which lymphocyte will Undergo clonal expansion, and Produce more lymphocytes If the same antigen enters the system again Memory B cells quickly divide Give rise to more lymphocytes capable of quickly producing antibodies 59 Structure of an Antibody 國立交通大學生物科技學系陳文亮老師 30

31 Structure of an Antibody 國立交通大學生物科技學系陳文亮老師 31

32 63 64 國立交通大學生物科技學系陳文亮老師 32

33 Overview of Nonspecific and Specific Defenses 65 Active Immunity Induced Immunity Immunization Pathogens or pathogen products treated to remove virulence Dependent upon memory B cells & memory T cells capable of responding to lower doses of antigen 66 國立交通大學生物科技學系陳文亮老師 33

34 Active Immunity Due to Immunizations 67 Passive immunity Passive Immunity Occurs when an individual is given prepared antibodies (immunoglobins) to combat a disease Short-lived Newborns are often passively immune due to mother s blood 68 國立交通大學生物科技學系陳文亮老師 34

35 Passive Immunity 69 Cytokines and Immunity Cytokines Signaling molecules produced by lymphocytes, monocytes, or other cells Both interferon and interleukins have been used as immunotherapeutic drugs Enhance the ability of the individual s T cells (and B cells) to fight cancer 70 國立交通大學生物科技學系陳文亮老師 35

36 Production of Monoclonal Antibodies 71 Allergies Immunity Side Effects Hypersensitivities to substances that ordinarily would not harm the body Immediate Response IgE antibodies Delayed Response Memory T cells 72 國立交通大學生物科技學系陳文亮老師 36

37 Immunity Side Effects Blood Type Reactions ABO blood typing Two self antigens - A and B If same antigen and its antibody are present in the blood, agglutination occurs Rh blood typing People that are Rh have Rh factor People that are Rh - do not have Rh factor Rh - individuals may produce antibodies to Rh factor if exposed 73 Blood Transfusions 74 國立交通大學生物科技學系陳文亮老師 37

38 Hemolytic Disease of the Newborn 75 Immunity Side Effects Tissue Rejection Antibodies and cytotoxic T cells bring about destruction of foreign tissues in the body Immune system is correctly distinguishing between self and nonself Autoimmune Diseases Cytotoxic T cells or antibodies mistakenly attack the body s own cells 76 國立交通大學生物科技學系陳文亮老師 38

39 Review The Lymphatic System Lymph Vessels Lymphoid Organs Nonspecific Defenses Barriers Inflammatory Response Specific Defenses Antibodies T Cells Induced Immunity Active versus Passive Immunity Immunity Side Effects Allergies Blood Typing 77 國立交通大學生物科技學系陳文亮老師 39

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