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Essentials of Human Anatomy & Physiology Seventh Edition Elaine N. Marieb Chapter 12- ppt 2 3rd line of defense AKA Immunity Pgs 389-390 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 3rd Line of Defense- T and B lymphocytes Review: •Antigen (Ag)- any substance that causes immune response (3rd line / “specific” defense) •Pathogens - viruses, bacteria, fungi, protein-hapten combo (allergen-pollen) are Ag’s •AMI (Humoral) – Antibody Mediated Immune Response carried out primarily by B Cells (and their antibodies) to attack extracellular pathogens (ex. bateria, fungi, viruses) •CMI – Cell Mediated Immune Response carried out primarily by T Cells (and their helpers) to attack intracellular pathogens (ex. cancer, transplanted tissue) Slide 12.17a Activation of Lymphocytes NOTE: Both T and B Cells (Lymphocytes) are made in Bone Marrow! 1. B Cells - stay in bone marrow to become “immunocompetent” T Cells - go to Thymus to become “immunocompetent” 2. Immunocompetent (but still Naïve) B & T Cells Travel to Lymph Nodes & other Lymphoid Tissues to face their “Antigen Challenge” in which they become Mature (Activated) 3. Mature B and T cells recirculate through blood & lymph ready to help you! Figure 12.9 Slide 12.30 Antibody Mediated Immune Response (AMI) – aka “Humoral” • AMI (“humoral”) 1. Extracellular Antigen (Ag) (ex. bacteria, extracellular viruses) is detected and MHC1 is presented by antigen presenting cell This leads to… 2. B lymphocytes (B cells) and their antibodies (Ab’s) attack the extracellular Antigens (Ags) by producing: 1. Plasma Cells 2. Antibodies 3. Complement Slide 12.17a Cell Mediated Immune Response (CMI) • CMI (cell mediated) 1. Phagocytosis of antigen (by macrophage) 2. Macrophage presents MHC2 Which lead to… 3. Helper T Cells (type of T cell) to trigger Cytotoxic T Cells to release their chemicals to attack intracellular Ag’s (ex. cancer, viral infected cells & transplanted tissue): Those Chemicals Include: • Lymphokines • Lymphotoxins • Interferon Slide 12.17a FYI ONLY •Remember…..If 1st line of defense fails, it leads to 2nd line, if 2nd line fails, it leads to 3rd line •In lymph nodes are T and B lymphocytes (cortex) and macrophages and other phagocytes (medulla) •Lymph nodes filter lymph and the macrophages/“phagocytes” are called antigen presenting cells (APC). •Phagocytosis (2nd line of defense) activates T and B cells (3rd line) which function in the cortex of lymph nodes Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.30 Antigen Determines Pathway!! Intracellular = CMI or Extracellular = AMI CMI IL-2 IL-1 AMI Figure 12.15 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.43 Macrophages (APC) DIRECT AMI or CMI: • IL-1 (Interleukin 1) - secreted by macrophages and Helper T cells to stimulate B cells (AMI) Antibody Mediated Immunity (Plasma Cells, Antibodies, complement, B memory Cells) • T Helper cells - circulate and recruit other cells to fight invaders; called the “directors” • IL-2 (Interleukin 2) - released by Helper T cells which stimulate cytotoxic T cells • Cytotoxic T cells - (CMI) Carry out Cell Mediated Immunity by making chemicals (below) when activated (Interferon, Lymphokines, Lymphotoxins, T memory cells ) Warm-Up (like a pyrogen ) On the chart, put the following descriptors into the correct category (either AMI or CMI or BOTH): B Cell Directed APC presents MHC2 Intracellular antigens T Cell Directed Helper T Cells involved APC presents MHC1 Extracellular antigens Uses Cytotoxic T Cells Stimulated by IL-1 APC involved CMI AMI Both Primary (first encounter) Vs Secondary Exposure (memory) (MHC2) ( w/ IL-2) Slide 12.17a Summary of Possible Immune Responses CMI AMI extracellular w/ MHC 1 w/ MHC 2 intracellular IL-1 Growth factor inhibits IL-2 Ts cell inhibits Antigen (2nd exposure) lymphokines lymphotoxin **interferon **complement Figure 12.16 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.45 CMI Immune Response macrophage (MHC2) Interferon, lymphotoxins , lymphokines produced Cytotoxic T Cells Slide 12.17a Summary of CMI CMI AMI 1. Antigen encounter 2. Macrophage presents MHC 2 to extracellular w/ MHC 1 Helper T cells which secrete IL-2 w/ MHC 2 intracellular Il-1 3. IL-2 stimulates Cytotoxic T cells (killer T cells)Il-2 Growth factor inhibits 4. Cytotoxic T cells Produce/stimulates T cell inhibits lymphokines, lymphotoxins and interferons (Some cytotoxic T cells alsoAntigen produce T (2nd exposure) memory cells s lymphotoxin lymphokines **interferon **complement Figure 12.16 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.45 Interferons, Lymphokines & Lymphotoxins Interferons •Made by infected cells as a “warning”! •Prevents viruses from infecting new healthy cells! Lymphokines Lymphotoxins • Stimulate additional Cytoxic T cells • Attract other WBC (produce more IL1 & IL2 • Enhance macrophages •Protein produced by T-cells and induces phagocytic cells to bind to invaders AMI Immune Response PREVIEW Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.32 1. Antigen encounter Summary of AMI 2. APCCMI secretes IL1 or presents MHC 1 AMI 3. Stimulates B cells to differentiate into Plasma extracellular w/ MHC 1 w/ MHC 2 intracellular cells (which produces Il-1 antibodies) which Growth factor Il-2 activate: • Phagocytosis inhibits T cell inhibits • Complement • Lysis Antigen (2nd exposure) • chemotaxislymphokines s **complement Figure 12.16 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings **interferon Note: Some B cells also differentiate into memory B cells lymphotoxin Slide 12.45 AMI: Antibody Mediated or Humoral Immunity (in Detail) • Extracellular Ag is detected by an APC (macrophage or Helper T cell) • B cells are activated • B cells differentiate into Memory B Cells or Plasma cells • Plasma Cells- synthesize Antibodies (Ig) • Antibodies - agglutinate (sticks to) with the antigen & activates: » Phagocytosis » Complement (inflammatory response and opsonization) » Lysis » Chemotaxis (& its resulting inflammation) Activation of Complement Made in 3rd line Acts in 2nd line Figure 12.14 inflammation Slide 12.41 Antibodies or Immunoglobulins: (Ab or Ig’s) • Antibodies (Ab’s) are proteins secreted by plasma cells (made from B Cells) Circulates in blood plasma Ab’s bind to a specific antigen (Ag) Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.37 Antibody (Ig) Structure Figure 12.13b 4 polypeptide chains (attached by disulfide bonds): •2 heavy •2 light •Variable region specific for Ag •Constant region determines type of Ig Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.38a 5 Types of Antibody (Ig) Classes M.A.D.G.E. IgM IgA IgD IgG IgE Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Types of Ig’s • Five major Ig classes: IgM – fixes complement Agglutination agent; pentamer IgA – in mucus membranes and their secretions, ex. milk, saliva, tears, etc. Monomer and dimer; prevents pathogen from entering body Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.39 Types of Ig’s • Five major Ig classes IgD – on B cells, activates other B cells IgG – crosses the placenta during pregnancy, fix complement. Most abundant monomers IgE – leads to allergies In skin, mucosae of resp tract, intestines, and tonsils Binds to mast cells & basophils & triggers the release of histamines and other chemicals that mediate inflammation Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.39 Monoclonal Antibodies Isolate one single B cell line that produces one kind of Ab Clone the Ab in a lab Examples of uses: Pregnancy tests Treatment for hepatitis, cancer, rabies Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.36 Primary and Secondary Responses Primary response and Memory Cells (1st exposure) causes Memory cells Gradual rise & rapid decline Rapid rise & remains high for some time illness AND memory cells made Secondary response is quicker for future exposures because memory cells are made during the primary response Figure 12.11 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.33 Vaccines Active Artificially Acquired Immunity Vaccination is a preventative shot that contains weakened or dead viruses that cause a primary response WITHOUT illness and memory cells are made protect against future exposures for secondary response Slide 12.33 Antibiotics Medicine given to kill bacterial infection, cannot be used for viral infections Must take it for full 7-10 days otherwise, bacterial infection can come back and/or can cause antibiotic resistance in bacteria Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.33 Antibiotic resistance Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.33 Why we get sick…why the symptoms The Ag’s attack and kill our cells We attack the Ag’s with our immune responses ex fever, inflammation, etc Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.34 Antiserum Animal’s Ab’s produced against an Ag that can be given to a human to protect it against same Ag Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 12.34 Types of Immunity Active – body makes memory as a result of an antigen challenge! Passive - B Cells are not challenged so no immunological memory…but you are “cured” for the time being Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings animal’s Ab’s (antiserum) Figure 12.12 Slide 12.34