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Introduction to The Immune System • Pin Ling (凌 斌), Ph.D. ext 5632; [email protected] • References: 1. Abbas, A, K. et.al, Cellular and Molecular Immunology, 6th ed., 2007 2. Male D., J. Brostoff, D. B Roth, and I. Roitt Immunology, 7th ed., 2006. Keys toward Learning Immunology • Lectures => Deliver the key concepts of Immunology. • Workbook => Apply the knowledge from Immunology to the solution of clinical problems. • Textbook reading => Help learn the details and build up comprehensive knowledge of immunology Evaluation For the Immunology Section: • Examination => 70 % • Attendance & Class performance => 30% Outline • The Origin of the Immune Concept • Overview of Immunity to Microbes • Features & Components of Innate & Adaptive Immunity • Summary & Question The Origin of Immune Concept 1. The term “Immunity” => Latin word “Immunitas” => Protection from legal prosecution (Roman senators) Biological definition => Protection from infectious diseases 2. The concept of immunity => existed in ancient Greek & Chinese => the experienced view Vaccination (also called Immunization)<=Vaccinia 3. The scientific view of immunity => Edward Jenner (1796) Observation => Milkmaids generally get No smallpox Hypothesis => Pus from vaccinia (cowpox) => Protect milkmaids from smallpox Test => Inoculate materials from cowpox pus => Protect a young boy from smallpox (Protective immunity) Eradication of smallpox Edward Jenner Vaccines for common infectious diseases Still no effective vaccines for many infectious microbes, ex. HCV, HIV, …..etc Outline • The Origin of Immune Concept • Overview of Immunity to Microbes • Features & Components of Innate & Adaptive Immunity • Summary & Question Key concepts about immunity-I 1. The immune system has evolved to protect us from the invasion of pathogens. Meanwhile, microbes have evolved to survive in the host. 2. Innate and adaptive immune responses (for vertebrates) => An integrated system of host defense => Cells & molecules function cooperatively Antigen-presenting cells => Lymphocytes => Effector cells 3. Innate immunity is the older host defense system: - Existed in both Invertebrates & Vertebrates - Provides the initial defense against infections - Activates and shapes adaptive immune responses Key concepts about immunity-II 4. Adaptive immunity evolved later: - Existed only in Vertebrates - Provides the more potent and diverse defense against infections - Better Develops understanding as a response to infection and adapts to the of Immunology infection Help manipulate immune responses immune Solve system the medical 5. The may fail =>problems Immunodeficiency, Hypersensitivity, & Autoimmune diseases. 6. Normal immune responses can be inconvenient in medical cases, ex. organ transplantation Overview of immune responses Innate vs Adaptive immunity The immune system has the ability to recognize some self components: -The Normal condition => prevent self-recognition -The Pathological “ “ => occur self-recognition Phagocytosis during innate immunity-I Phagocytosis during innate immunity-II Inflammation =>A hallmark of innate immunity =>Local accumulation of immune cells & molecules against microbes =>Function to eliminate infections but often cause tissue damage & disease Interaction between innate and & adaptive immunity 1. Innate immunity => Ag presentation (by infected cells) 2. Adaptive immunity => Ag recognition (by T & B lymphocytes) Overview of adaptive immune responses Outline • The Origin of Immune Concept • Overview of Immunity to Microbes • Features & Components of Innate & Adaptive Immunity • Summary & Question Features of Adaptive immunity Specificity, memory, and homeostasis of adaptive immunity Clonal expansion of lymphocytes Types of adaptive immunity 1. Humoral immunity => Molecules in body fluid, ex. Antibody (Ab) => Key player => B cells => Target extracellular For innate immunity, it microbes & toxins Cellular components for 2. Cell-mediated immunity => Key player => T cells => regulate other immune cells => Target intracellular microbes, ex. viruses, bacteria also includes Humoral & immune defense Active vs. Passive immunity Active immunity => A host response to a microbe (Ag) => specific and long-term immune defense (memory) Passive immunity => Adoptive transfer of Ab or lymphocytes specific for a microbe (or Ag) => specific, instant but transient immune defense Serum therapy => Humoral immunity & Passive immunity Serum (Ab) from animals recovered from diphtheria infection => Naïve animals => Resistant to diphtheria infection Key concepts in innate immunity 1. The innate immune system mainly recognizes common structures shared by classes of microbes. 2. Microbial common structures => Pathogen-Associated Molecular Patterns (PAMPs), ex. LPS, Peptidoglycan, Microbial DNA & RNA. 3. Receptors that recognize PAMPs are called PatternRecognition Receptors (PRRs). 4. PRRs are encoded in germline DNA => limited Diversity 5. PRRs may also recognize components from injured or dead host cells => Autoimmune diseases Examples of PatternRecognition Receptors (PRRs) Toll-like Receptors Locations of Different PRRs Body fluids -Soluble PRRs Cellular PRRs - Cell surface - Endosomes - Cytosol Soluble Pattern Recognition ReceptorsComplement activation pathways Epithelial barriers prevent the entry of microbes Cellular components of the immune system will be discussed extensively in Lecture #2. Failure of the immune system Ineffective response -Immunodeficiency Overactive response -Hypersensitivity Auto-reactive response -Autoimmunity Outline • The Origin of Immune Concept • Overview of Immunity to Microbes • Features & Components of Innate & Adaptive Immunity • Summary & Question SUMMARY 1. Protective immunity against microbes is mediated by the early response of innate immunity and the later response of adaptive immunity. 2. Innate immune responses are initiated by recognition of common microbial structures (PAMPs) by - Provide the first line of host defense - Activate and regulate the adaptive immunity 3. Adaptive immune responses are initiated by recognition of foreign antigens by specific lymphocytes. - Provide more potent, specific (Ag), & broad protection - Develop immune memory for next exposure - Feedback regulate innate immunity Questions 1. Why is it necessary to vaccinate against tetanus only every 10 years, though antibodies against the toxoid disappear from the circulation within a year? 2. Why is the vaccine against tetanus always effective, whereas the vaccine against influenza protects on some occasions but not others? The End & Thank you