Introduction to Immunology PDF

Introduction to Immunology Dr. Ashutosh Verma, BVSc, MVSc, PhD, DipACVM Professor and Associate Dean of Basic Sciences and Research Richard A. Gillespie College of Veterinary Medicine Lincoln Memorial University, Harrogate, TN, USA  Disclaimer...

Introduction to Immunology Dr. Ashutosh Verma, BVSc, MVSc, PhD, DipACVM Professor and Associate Dean of Basic Sciences and Research Richard A. Gillespie College of Veterinary Medicine Lincoln Memorial University, Harrogate, TN, USA  Disclaimer The material in this presentation has been obtained from different sources including books, published papers and online resources. It is intended only for educational purposes. Most of the presented material comes from the following: i. Veterinary Immunology by Tizard 10th ed. ii. Basic Immunology by Abbas et al. 4th and 5th ed. iii. Janeway’s Immunobiology  Learning Objectives 1. Describe innate and adaptive immunity and list their differences. 2. List major components of the innate and adaptive immunity. 3. Describe the two main arms of the adaptive response. 4. Define antigen, antibody and cytokines. 5. Briefly explain memory and tolerance as it pertains to the adaptive immunity.  Lecture Outline Introduction to the course History of Immunology Microbial invasion Body’s defenses- overview of innate and adaptive immunity Introduction to the course  Course Description This course presents current concepts in basic and clinical immunology with special emphasis on protective immunity against infectious diseases and the role of aberrant immune responses in disease.  Course Goals The primary goal of this course is to provide students with an understanding of basic mechanisms of veterinary immunology, thereby giving them the tools to keep up with developments in the field and help in solving clinical immunological problems throughout their careers. 1 Introduction to Immunology Dr. Verma Instructors 2 Cells and Tissues of the Immune System Dr. Verma 3 Innate Immunity: Early Recognition of Foreign Invaders Dr. Verma 4 Innate Immunity: Inflammation Dr. Verma 5 Innate Immunity: Phagocytosis Dr. Verma 6 Innate Immunity: The Complement System Dr. Verma 7 Cytokines and Their Receptors Dr. Verma 8 Triggers of Adaptive Immunity Dr. Verma 9 DCs and Antigen Processing Dr. Verma 10 MHCs Dr. Verma 11 Lymphocytes Dr. Verma 12 Helper T cells and Their Response to Antigen Dr. Verma 13 B cells and Their Response to Antigen Dr. Verma 14 Structure and Function of Antibodies Dr. Verma 15 Immunoglobulin Genes and Generation of Diversity Dr. Verma Dr. A. Verma 16 T Cell Function and Destruction of Cell Associated Invaders Dr. Verma 17 Regulation of Adaptive Immunity I Dr. Verma 18 Regulation of Adaptive Immunity II Dr. Verma 19 The Microbiota and the Immune System Dr. V. Faulkner 20 Immunity to Bacteria and Fungi Dr. V. Faulkner 21 Immunity to Viruses Dr. V. Faulkner 22 Evasion of Immune Response by Pathogens Dr. V. Faulkner 23 Immunity to Parasites Dr. V. Faulkner 24 Neonatal Immunity Dr. Phillips 25 Mucosal Immunity Dr. Phillips 26 Vaccination Dr. Phillips 27 Transfusion Immunology Dr. Phillips 28 Type I Hypersensitivity Dr. V. Faulkner Dr. V. Faulkner 29 Type II and III Hypersensitivity Dr. V. Faulkner 30 Type IV Hypersensitivity Dr. V. Faulkner 31 Tumor Immunology Dr. Phillips 32 Self-Tolerance and Autoimmunity Dr. Phillips 33 Immunodeficiency and Immunological Defects Dr. Phillips 34 Systemic Immunological Diseases Dr. Phillips 35 Immunotherapeutics Dr. Phillips 36 Immunodiagnostics Dr. Phillips 37 Review Dr. Phillips Dr. J. Phillips  Immunology Exams Exam 1- Jan 27 (Lectures 1-12) Exam 2- Feb 10 (Lectures 13-25) Exam 3- Mar 3 (Lectures 26-36) Final Exam- May (Lectures 1-36) The final grade for the course will be based upon four noncumulative examinations (80%), a final exam (10%) and a writing assignment (10%). NOTE: Please refer to Canvas for any updates on exam dates as they may change as the semester progresses. Expectations? Importance of the Immune System History of Veterinary Immunology  History of Veterinary Immunology  12th century: Smallpox variolation  1754: Rinderpest inoculations  1798: Edward Jenner; cowpox; term ‘vaccination’  1879: Pasteur’s fowl cholera experiment (details on next slide); anthrax and rabies vaccines  Daniel Salmon and Theobald Smith: dead organisms can make effective vaccines  Von Behring and Kitasato: bacterial products also protective  Pasteur’s fowl cholera experiment Birds inoculated with an aged culture of Pasteurella multocida did not die. However, when subsequently inoculated with a fresh culture of virulent P. multocida, the birds were found to be protected. It was this experiment that launched the science of immunology. Microbial invasion  Microbial invasion Enormous number of microorganism colonize body surfaces  Microbial invasion Commensals: colonize body surfaces but do not invade the body and don’t normally cause disease Pathogen: organism that can cause disease Primary pathogen: cause disease every time it invades body, even in small numbers. eg. HIV and Brucella abortus Opportunistic pathogen: cause disease only when administered in high doses. e.g. Mannheimia hemolytica and Pneumocystis jiroveci  Body’s Defenses - Overview of Innate and Adaptive immune Defense  Body’s Defenses Complex, interacting networks of biochemical and cellular reactions No immune response is restricted to a single biochemical mechanism or pathway Redundant and multiple mechanisms work together to ensure microbial destructions  Innate and Adaptive Defenses The basic arrangement of the innate and adaptive immune systems. Innate immunity is the first line of defense; adaptive immunity backs it up.  Innate and Adaptive Defenses Innate defense Protects previously unexposed animal Immediate protection Not specific Activated by Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) Provide important signals for adaptive immune response Adaptive defense Develops days to weeks after exposure Specific Memory Tolerance Enhance innate immune response Components of Innate and Adaptive defenses Innate defense 1. Physical/chemical barriers 2. Phagocytic and sentinel cells 3. Complement system 4. Innate defense cytokines 5. Natural killer (NK) cells Adaptive defense 1. Humoral immunity (antibodies) 2. Cell-mediated immunity (T-helper cells, Cytotoxic T cells, and Gamma delta (γδ) T cells).  Components of Innate defense 1. Physical/chemical barriers 2. Phagocytic and sentinel cells 3. Complement system 4. Innate defense cytokines 5. Natural killer (NK) cells  Innate Defense 1. Physical/chemical barriers Epithelial barriers (skin, mucus membrane) Normal microflora Acid environment in stomach Antimicrobial peptides  Innate Defense 2. Phagocytic and sentinel cells Phagocytic cells: ingest and kill pathogens Examples- Neutrophils and Macrophages Sentinel cells: resident tissue cells that detect invasion by recognizing PAMPs and DAMPs Examples- Dendritic cells (DC), Macrophages, Mast cells  Innate Defense 3. Complement System An enzyme cascade system that has antimicrobial activity Series of 20-30 proteins in blood plasma Rapidly induced Multiple mechanisms for controlling infection Potent; harmful if not regulated  Innate Defense 4. Innate defense cytokines Cytokines: protein messenger molecules that can act on other cells or the cell that produced it. Proinflammatory cytokines: secreted by sentinel cells in response to PAMPs and DAMPs. Cause fever, lethargy, and loss of appetite. Examples- Interleukin (IL)-1, IL-6 and TNF. Chemokines: cause cells to migrate to sites of infection, some are produced by sentinel cells. Interferons: interferes with replication of some viruses; produced by virally infected cells.  Innate Defense 5. Natural killer (NK) cells Lymphocyte that is part of innate immunity Kill virus infected cells and tumor cells Recognize and kill cells that do not express normal proteins  Summary of Innate Defense Rapid Critical first line of defense Efficient; works most of the time No memory Can work independently of adaptive immunity but enhanced by adaptive immunity  Components of Adaptive defense 1. Humoral immunity - Antibodies 2. Cell-mediated immunity - T-helper cells - Cytotoxic T cells - Gamma delta (γδ) T cells  Adaptive Defense 1. Humoral immunity Named so because transfer of body ‘humors’ from protected animal to naïve animal could provide protection B cells or B lymphocytes produce antibodies Antibody = Immunoglobulin = Ig IgM, IgG, IgA, IgE  Adaptive Defense 2. Cell-mediated immunity (CMI) Named so because transfer of cells from protected animal to naïve animal could provide protection Two major classes of T cells based on T-cell receptors 1. Alpha Beta (αβ) T cells Examples: T-helper cells, Cytotoxic T cells 2. Gamma Delta (γδ) T cells Principal Mechanisms of Innate and Adaptive Immunity The mechanisms of innate immunity provide the initial defense against infections. Some mechanisms (e.g., epithelial barriers) prevent infections, and other mechanisms (e.g., phagocytes, natural killer [NK] cells, and the complement system) eliminate microbes. Adaptive immune responses develop later and are mediated by lymphocytes and their products. Antibodies block infections and eliminate microbes, and T lymphocytes eradicate intracellular microbes. The kinetics of the innate and adaptive immune responses are approximations and may vary in different infections. Time course of Innate and Adaptive Immunity  Adaptive Defense A few more things...  Antigen recognition  Immunologic Memory  Tolerance  Adaptive Defense A few more things... Antigen processing cells (APCs) APCs - Dendritic cells,  Antigen recognition macrophages, B-cells Different from recognition by innate cells  Immunologic Memory  Tolerance  Adaptive Defense A few more things...  Antigen recognition  Immunologic Memory  Tolerance  Adaptive Defense A few more things...  Antigen recognition  Immunologic Memory  Tolerance: Protecting ‘self’ from immune system Can develop against ‘non-self’ antigens too, under certain conditions Comparison of Innate and Adaptive Immunity INNATE IMMUNITY ADAPTIVE IMMUNITY Cells engaged Macrophages, dendritic T and B cells cells, neutrophils, natural killer cells Evolutionary history Ancient Recent Onset Rapid (minutes to hours) Slow (Days to weeks) Specificity Common microbial Unique antigens structures Potency May be overwhelmed Rarely overwhelmed Memory None Significant memory Effectiveness Does not improve Improves with exposure  Key concept 1 The immune system protects animals against microbial invasion and is therefore essential for life.  Key concept 2 Multiple mechanisms are needed to ensure freedom from invasion: Innate immunity Adaptive immunity  Key concept 3 Major defense mechanisms are linked to form complex interacting networks.  Key concept 4 There are two types of adaptive immunity: Humoral Cell-mediated  Key concept 5 Humoral immunity is mainly directed against bacterial invaders and is mediated by antibodies. Antibodies circulate in body fluids, especially in the bloodstream. They bind to bacteria and mark them for destruction.  Key concept 6 Cell mediated immunity regulates innate and adaptive responses through cytokines and employs cells that destroy abnormal cells such as those infected by viruses.  Key concept 7 The adaptive immune response can remember prior exposure to foreign invaders and mount a faster and effective response on subsequent exposure to the same invader.