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BASIC PRINCIPLES OF ADAPTIVE IMMUNITY AND IMMUNIZATION
CHAPTER 17 Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Adaptive (Acquired) Immunity
Natural Artificial Active Passive Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Antigen Characteristics
Antigens Foreign molecules Epitopes Molecular determinants on Ag May be multiple on one Ag Haptens Small Ag Sometimes cause allergies Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Immune System Compartments
B lymphocytes 10% of circulating lymphocytes Antibody production Humoral Immune compartment T lymphocytes 75% of circulating lymphocytes Cell-mediated immune compartment 2 major sub-types Helper T cells Cytotoxic T cells Natural Killer cells No clonal stimulation Cause lysis and apoptosis of pathogenic cells Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Protection and Development
Humoral Immunity Antibody production by B cells Bacteria, toxins and viruses Cell-mediated Immunity Cell lysis, apoptosis Foreign eukaryotic cells Virally infected Fungal, protozoan, helminthic Cancer Transplanted organs Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Immune system Properties
Self versus Non-self Recognition Maturation leads to Clonal Deletion Defects = autoimmune disease Specificity Random gene rearrangements create potential binding sites for antigens Some cross-reactivity Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Immune System Properties
Diversity Over 1 billion antigen binding sites are possible Memory Sub-populations of stimulated lymphocytes remain in lymph nodes to provide a faster, larger response on second antigen encounter Basis of “Immunity” or the anamnestic (secondary/ memory) response Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Humoral Immunity B lymphocyte binds Ag
Bound Ag is engulfed and fragmented within the B cell Ag fragments + Major Histocompatibility Complex Type II (MHC II) proteins together = presented or “processed” antigen Triggers Interleukin 2 (IL-2) production from T cells This stimulates B cells further and creates memory cells Known as T-dependent Ag, usually proteins Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Antibody Structure Heavy/Light Chains Variable/Constant Regions
Antigen Binding Site Disulfide Bridges (Bonds) Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Immunoglobulin (Ig) Classes
Ig G Main serum Ab Produced in 2o response Transplacental Activates complement and phagocytes IgA Secreted Abundant in colostrum Protected by secretory component Activates complement Ig M Large molecules First to be produced Indicative of recent infection Ig E (reagin) Bound to mast cells and basophils Triggers allergic responses Ig D Not well understood May trigger allergic responses High levels in autoimmune disease
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Immune Response Types Primary Response IgM initially
IgG detectible in 2-3 weeks Levels may drop after initial exposure Memory cells persist Secondary / Memory Response Much larger response of IgG Protection against invading microbes and toxins Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Antigen Types T-independent No helper T cells
No memory cells are created Only IgM Carbohydrate Ag, often capsular on bacteria T-dependent Needs helper T cells Creates memory B cells IgM and IgG Protein Ag Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Antibody Effects Agglutination Target count reduction
Complement mediated effects FC fragment (Constant region) activates complement Cytolysis Opsonization Increased inflammation Neutralization Viral and bacterial binding sites for host cell attachment are blocked Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Monoclonal Antibodies
Multiple myeloma cells + normal lymphocytes Hybrid cells Immortal in large-scale cell culture Specific Ab producers Uses Diagnostic Anticancer Anti-tissue rejection Allergies to mouse proteins are a challenge Humanized Mabs Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Cell Mediated Immunity
Processed antigens presented alongside MHC proteins TH cells are activated by Ag + MHC II, on antigen presenting dendritic cells, B cells or macrophages TC cells are activated by Ag + MHC I , usually on infected cells with intracellular virus or bacteria, transformed cells or transplant cells Memory T cells can form Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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TH Cell activity Helper T cells (TH) release lymphokines IL-2
stimulates Ab production Activates TC cells Gamma IFN Co-ordinates inflammatory response Antiviral and anti-tumor Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Tc Cell activity Activation Ag + MHC I Cell lysis Perforins
Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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NK Cells – Innate Immunity
Natural Killer cells Produce Perforin proteins Lyse tumor and bacterially infected cells Induce apoptosis Activated by lack of MHC Class I proteins on cell membranes, no clonal stimulation NK cell video clip Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Mucosal Immune System MALT Mucosal associated lymphoid tissue GALT
Gut associated lymphoid tissue M cells Mucosal cells that transfer antigens to antigen presenting lymphocytes Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Factors Modifying Immune System Health
Genetic factors Age Season Diet Exercise Sleep deprivation Pregnancy Trauma Environment Medications Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Immunization Types ACTIVE PASSIVE Ag administration
Toxoid or microbial structural molecule Whole cell killed Attenuated Subunit Recombinant DNA vaccines Live vaccines provide longer protection Route of administration affects protection level Ab administration Immune serum globulin Antitoxins Antivenins Temporary, protection declines Will affect the course of a disease Allergic reactions are commonest drawback Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Ideal Vaccine Qualities
Protective Safe Sustained effects Generate active immunity Stable shelf life Affordable Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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Immunity to Different Pathogens
Bacteria B cell Ab production Viruses T cell attack of virally infected cells Fungi T cell attack of fungi Protozoa/Helminths T cell attack of protozoa and worms Eosinophil Responses Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.
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