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Dr. Fang-Ping Huang Department of Pathology, Immunology Division, Room 216 Tel. 2855 4864 Email: fphuang@hkucc.hku.hk
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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 Advances 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 system – an overview
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Basic concepts in Immunology Organisms and microorganisms –Bacteria, viruses, fungi & parasites Infections and diseases Infection == 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 of the 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 19 th 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 of the immune system Immune cells are bone marrow-derived, & distributed through out the 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 system following 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 1 st infection memory 2 nd infection slow response fast response pathogen proliferate pathogen killed disease no disease symptoms no symptom
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Memory & specificity – key features of the adaptive immunity
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Immunological memory & vaccination Natural infections: 1 st infection memory 2 nd infection slow responsefast response pathogens multiplypathogens disposed Symptoms/diseaseno disease Vaccination memory nature infections no disease fast response pathogens disposed no disease
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Vaccination protects us from infection by inducing the adaptive immune response, but bypassing the need for a primary infection
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Theoretical basis for immunological specificity and memory Theory of Clonal Selection Establishment of lymphocyte memory pool
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12 43 Ehrlich’s “Side-chain Hypothesis” (1900)
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Burnet’s “Clonal Selection” Theory Each lymphocyte produces one type of Ag receptors only, antigen selects and stimulates cells carrying receptors specific for the antigen 1n2 222 22 2
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s s s s s s s
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Immunological memory The ability of the immune system to respond more rapidly and effectively to specific pathogens that have been encountered previously. Reflection of the pre-existence of a clonally expanded population (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 (T H ) 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 Cells work chiefly by secreting soluble substances known as 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 for recognition by other immune cells (e.g. phagocytes) Antibody functions
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Tc Target Tc
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T H 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 body’s own tissues/cells - self tolerance –to pathogen-derived/foreign Ags
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The concepts of immunological ‘ self ’ & ‘ non-self ’ Immune system does not attack self tissues or cells under 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 responses simply to anything that is “non-self”? A question for thoughts:
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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 T H 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 for primary infection Immunological tolerance: Tolerance induction is Ag specific Central & peripheral mechanisms Summary
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