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3110302 Veterinary Immunology Course syllabus ประมวลรายวิชา วิทยาภูมิคม ุ กันทางสัตวแพทย (Veterinary Immunology) รหัสวิชา 3110302 จํานวนหนวยกิต 3 (2 - 3 - 4) ชื่อวิชา วิทยาภูมค ิ ุมกันทางสัตวแพทย (Veterinary Immunology) ชื่อผูส อน รศ.สพ.ญ.ดร.สันนิภา สุรทัตต ผศ.น.สพ.ดร.เดชฤทธิ์ นิลอุบล รศ.น.สพ.ดร.โสมทัต วงศสวาง 1 References 2004 2009 2003 2005 2006-7 No where to start ? 2 Introduction to Immunology Sanipa Suradhat, D.V.M., Ph.D. Definitions Immunology: The study of the immune system and its response to invading pathogen Immunity: Resistance to disease, specifically infectious disease The immune system: Collection of cells, tissue, and molecules that mediate resistance to infections. The coordinated reaction of these cells and molecules to infectious microbes is the immune response. The physiologic functions of the immune system is to prevent infections and to eradicate established infection. 3 Figure 1-1 Timeline of Immunology 1798 First demonsration of vaccination smallpox vaccination (Edward Jenner) 1862 - phagocytosis (Ernst Haeckel) 1876 - First demonstration that microbes can cause disease-anthrax (Robert Koch) 1877 - Mast cells (Paul Ehrlich) 1880-1 -Theory that bacterial virulence could be attenuated by culture in vitro and used as vaccines. Used to make chicken cholera and anthrax "vaccines" (Louis Pasteur) 1883 - 1905 - Cellular theory of immunity via phagocytosis by macrophages (Elie Metchnikoff) 1885 - First report of a live "attenuated" vaccine for rabies (Louis Pasteur) 1900 - Antibody formation theory (Paul Ehrlich) 1917 - hapten (Karl Landsteiner) 1924 - Reticuloendothelial system 1938 - Antigen-Antibody binding hypothesis (John Marrack) 1942 - Adjuvants (Jules Freund and Katherine McDermott) 1957 - Clonal Selection theory (Frank Macfarlane Burnet) 1798 1900 2000 4 Timeline of Immunology 1958-1962 - Discovery of human leukocyte antigens 1959-1962 - Discovery of antibody structure 1964-1968 T and B cell cooperation in immune response 1972 - Structure of the antibody molecule 1974 - T-cell restriction to major histocompatibility complex (Rolf Zinkernagel and Peter Doherty) 1975 - Generation of the first monoclonal antibodies (George Kohler and Cesar Milstein) 1976 - Identification of somatic recombination of immunoglobulin genes (Susumu Tonegawa) 1983 - Discovery of the T cell antigen receptor TCR (Ellis Reinherz, Philippa Marrack and John Kappler, James Allison) 1985-1987 - Identification of genes for the T cell receptor 1950 1975 2000 Hepatitis B vaccine produced by genetic engineering - 1986 Th1 vs Th2 model of T helper cell function (Timothy Mosmann) - 1986 'Danger' model of immunological tolerance (Polly Matzinger) - 1994 Regulatory T cells (Shimon Sakaguchi) - 1995 Identification of Toll-like receptors - 1996-1998 Discovery of FOXP3 - the gene directing regulatory T cell development - 2001 Development of human papillomavirus vaccine (Ian Frazer) - 2005 Nobel laureates 1901 Emil Adolf von Behring (1854-1917), "for his serum therapy to treat diphtheria" (First ever Nobel Prize in Physiology or Medicine) 1908 Eli Metchnikoff (1845-1916) and Paul Ehrlich (1854-1915), "for study of the immune system" 1919 Jules Bordet (1870-1916), "for discovery of the complement system in the immune system" 1930 Karl Landsteiner (1868-1943), "for discovery of human blood types" 1960 Peter B. Medawar (1915-1987) and Frank Macfarlane Burnet (1899-1985), "for the discovery that the immune system of the fetus learns how to distinguish between self and non-self" 1972 Gerald Maurice Edelman (1929-) and Rodney Robert Porter (1917-1985), "for discovering the chemical structure of antibodies" 1980 Baruj Benacerraf (1920-), Jean Dausset (1916-) and George Davis Snell (1903-1996), "for discovery of the Major histocompatibility complex genes which encode cell surface molecules important for the immune system's distinction between self and non-self" 1984 Niels Jerne (1911-1994), Georges J. F. Köhler (1946-1995) and César Milstein (1927-2002) "for work on the immune system and the production of monoclonal antibodies“ 1987 Susumu Tonegawa (1939-), "for discovering how the large diversity of antibodies is produced genetically" 1989 J. Michael Bishop (1936-) and Harold E. Varmus (1939-), "for discovering the cellular origins of retroviral oncogenes" 1996 Peter C. Doherty (1940-) and Rolf M. Zinkernagel (1944-) "for describing how MHC molecules are used by white blood cells to detect and kill virus-infected cells." 5 In 1980 the World Health Organization Global Commission for the Certification of Smallpox declared a worldwide eradication. Figure 1-33 6 Basic Concepts in Immunology 7 Cells of the immune system CD4+ CD8+ Layers of body defenses Invading microorganisms Physical barriers Examples: skin, enzymes, self-cleaning, normal flora Innate immunity Examples: Inflammation, phagocytes Specific/adaptive immunity Examples: antibody production, cell-mediated immunity The 3 general ways by which the animal body defends itself against microbial invasion 8 Time course Level of protection Physical barrier Adaptive immunity Innate immunity Minutes Hours Days Time 9 Innate immunity Abbas et al., 2000 Macrophage Attacking E.coli PAM vs bacteria Dendritic cells vs yeasts Neutrophil engulfing bacteria; www.wadsworth.org 10 Principle mechanisms of innate and adaptive immunity Abbas & Lichtman, 2004 Innate & specific immune responses Innate Immunity Specific Immunity Response is antigen-independent Response is antigen-dependent There is immediate maximal response There is a lag time between exposure and maximal response Not antigen-specific Antigen-specific Exposure results in no immunologic memory Exposure results in immunologic memory 11 Innate & specific immune responses Features Innate Specific Characteristics Relatively low Limited, PRRs (TLR) Relatively stereotypic No Immediately High Large Highly specialized Yes Delayed Physical and chemical barriers Skin, mucosal epithelium Anti-microbial chemicals Blood Proteins Cells Complement Phagocytes, Neutrophils NK-cells Cutaneous and mucosal immune system, secreted Abs Antibodies Lymphocytes Specificity Diversity Specialization Memory Action time Components Innate immunity and inflammation Adaptive Adaptive immunity immunity www.medscape.com 12 13 Clonal selection theory Abbas & Lichtman, 2004 14 Essential feature of adaptive immunity Foreign material (antigen) Antigen presenting cells Antigen-specific B cells Memory cell Antigen-specific T cells Antibody producing cell Effector T cell Humoral Immunity Cell-mediated immunity Memory cell Antigen elimination Adaptive (acquired) immunity Humoral immunity Cell-mediated immunity Abbas et al., 2000 15 Figure 3-11 16 Here’s how we fight the intruders Pathogen Pathogen attacks attacks Security Security breached breached Sentinel Sentinel cells cells sending sending SOS SOS Inflammation APC migration (APC leave the crime scene) Phagocytic cell entering the site Killing and clearing of invaders Pathogen clearance & Tissue repair Effector cells entering the site Activation of adaptive immunity In the lymphoid tissues Immediate Immediate action action Back Back up up plan plan Phase of immune response 17 Figure 1-20 Properties of adaptive immunity Property Significance for immunity to microbes Specificity Ability to recognize and respond to many different microbes Memory Enhanced responses to recurrent or persistent infections Specialization Responses to distinct microbes are optimized for defense against these microbes Nonreactivity to self antigens Prevent injurious immune responses against host cells and tissues Abbas and Lichtman, 2004 18 The balancing act The good - Transplant accepted - Reduced autoimmunity - Reduced allergy - Tumor immunity - Protection from infectious diseases Tolerance Immunosuppression Immunity Immune regulation - Compromised tumor immunity - Danger from infectious diseases - Transplant rejection - Autoimmunity - Allergy The ugly Adapted from Martin and Bachmann, 2006. In: Immunopotentiators in modern vaccines. Academic Press. The two-sided sword Tizard, 2004. In: Veterinary Immunology 19