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The Adaptive Immune System - An Overview

Jun 02, 2018

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    Dr. Fang-Ping Huang

    Department of Pathology,

    Immunology Division, Room 216Tel. 2855 4864

    Email: [email protected]

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    The immune system - an overview (basic concepts, features)

    Developmental biology of the immune system (Dr. L. Lu)

    Recent advances in lymphocyte lineage commitment (Dr. L. Lu) Apoptosis & the molecular cell death pathways (Dr. L. Lu)

    Antigen recognition by T cells & its MHC restrictions

    Pathways of antigen processing, presentation & co-stimulations Dendritic cells & the initiation of immune responses

    Immune regulation & dys-regulation in health & in diseases

    Essence and dvances in Contemporary Immunobiology

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    Basic concepts in immunology Vaccination & the history of immunology

    Types of immunity The adaptive immune system

    Immunological specificity & memory B cells & humoral immune response T cells & cell-mediated immune response

    The concepts of self/non-self & self -tolerance

    The immune systeman overview

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    Basic concepts in Immunology

    Organisms and microorganisms Bacteria, viruses, fungi & parasites

    Infections and diseasesInfection == disease

    Mechanisms of defense The immune system

    Cells & soluble factors

    Immunity and Immunology

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    Immunity

    Original meaning: exemption from taxes

    Other extended meaning: diplomatic immunity

    In the context of Immunology: collective mechanisms against diseases

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    Edward Jenner(1749-1823)

    &The Discovery of

    Vaccination (1796)

    Vaccinia (cowpox)&

    human smallpox

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    Eradication of smallpox (1979, WHO)

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    Vaccination

    A process of induction of immunity to a pathogen by

    deliberate injection of a weaken, modified or related form ofthe pathogen which is no longer pathogenic.

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    Other historic events & important findings:

    L. Pasteur (1880s) Vaccines against cholera, and rabies R. Kock (late 19th century)

    Infections caused by microorganisms

    P. Ehrlich et al. (1890s) Serum factors transfer of immunity

    Behring & Kitasato (1890s) Antibodies in serum bound to pathogens

    Porter & Edelman (1960s) Antibody structure

    J. Gowans (1960s) Immunological importance of lymphocytes

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    Size of the immune system?

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    Dendritic cell(sentinel)

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    Lymph Node

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    The bursa of Fabricius in birds

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    Cells, tissues and organs ofthe immune system

    Immune cells are bone marrow-derived, & distributed through outthe body

    Primary lymphoid organs: Thymus: T cell maturation Bone marrow (bursa of Fabricius in birds): B cell maturation

    Secondary lymphoid organs: Lymph nodes Spleen Mucosal lymphoid tissues (lung, gut)

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    Questions:

    How may vaccines protect us from infections?

    What may actually occur in our immune systemfollowing a vaccination?

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    Types of immunity

    Innate (natural) immunity Phagocytes etc.

    Early, rapid responses, but limited &non-specifc

    Adaptive (acquired) immunity Lymphocytes (B & T cells) Take time but powerful - specificity + memory

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    Measles attacks & immunological memory

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    Memory in adaptive immunity

    1st infection memory 2nd infectionslow response fast response

    pathogen proliferate pathogen killeddisease no diseasesymptoms no symptom

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    Memory & specificity key features of the adaptive immunity

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    Immunological memory & vaccination

    Natural infections:1st infection memory 2nd infectionslow response fast response

    pathogens multiply pathogens disposedSymptoms/disease no disease

    Vaccination memory nature infectionsno disease fast response pathogens disposedno disease

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    Vaccination protects us from infection byinducing the adaptive immune response, butbypassing the need for a primary infection

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    Theoretical basis for immunologicalspecificity and memory

    Theory of Clonal Selection Establishment of lymphocyte memory pool

    Eh li h Sid h i H h i

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    1 2

    43

    Ehrlichs Side -chain Hypothesis (1900)

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    Burnets Clonal Selection Theory Each lymphocyte produces one type of Ag receptors only, antigen selects and

    stimulates cells carrying receptors specific for the antigen

    1 n2

    222

    22

    2

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    s

    s s s s s s s s

    s s s s s s s ss s s s s s s s s s s s s s s s

    s s s s s s s s

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    Immunological memory

    The ability of the immune system to respond morerapidly and effectively to specific pathogens that havebeen encountered previously.

    Reflection of the pre-existence of a clonally expandedpopulation (pool) of antigen specific lymphocytes.

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    Humoral immune responses

    B cells and antibodies

    Cell mediated immune responses Cytotoxic T cell (Tc) Helper T cells (TH)

    The adaptive immune mechanisms

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    The Immune Recognition Molecules

    of the Adaptive Immune System

    1. Immunoglobulin (Ig)- B Cell Receptor (BCR)- Antibody (Ab)

    2. T Cell Receptor (TCR)

    3. Major Histocompatibility Complex (MHC)

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    B Cellswork chiefly by secretingsoluble substances knownas antibodies (Ab)

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    Ab basic structure

    domains

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    Ab V and C regions

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    Neutralization: e.g. toxins, viruses

    Opsonization: bind pathogens forrecognition by other immune cells

    (e.g. phagocytes)

    Antibody functions

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    Tc

    TargetTc

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    TH cells play a central role in the immune system

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    TH cells play a central role in the immune system

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    CD4 + T cells in HIV infection

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    Immunological tolerance

    A state of unresponsiveness to a particular Ag - Ag specific

    to Ags derived from bodys own tissues/cells- self tolerance to pathogen-derived/foreign Ags

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    The concepts ofimmunological self & non-self

    Immune system does not attack self tissues or cellsunder normal condition, but how?

    Central tolerance thymic education

    Peripheral tolerance failed-safe mechanisms

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    Early in life (foetal stage)

    T cells are important, which develop in the thymus

    TCR specificities: randomly generated many auto-reactive

    T cells recognize self components (Ag) in the thymus removed

    Non-self reactive cells selected, matured & exported

    Central tolerance thymic education

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    Post- thymic continuing education not all self Ags present in the thymus

    some auto-reactive cells can escape

    Mechanisms: Deletion

    Inactivation (anergy) Suppression

    Peripheral tolerance

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    Does the immune system mount responsessimply to anything that is non-self?

    A question for thoughts:

    Summary

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    Immunity: Innate (natural) Adaptive (acquired)

    Humoral (B cells, Abs) Cellular (T, NK, MQ)

    The adaptive immunity: Key features: specificity & memory Types: humoral & cell-mediated responses Key players: T & B lymphocytes TH cells play a central role in the induction & maintenance of immune responses

    Principle of vaccination: Vaccination protects us from infection by inducing protective immunity, through

    establishment of specific immunological memory but bypassing the need forprimary infection

    Immunological tolerance: Tolerance induction is Ag specific Central & peripheral mechanisms

    Summary