* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Modeling the Immune System
Major histocompatibility complex wikipedia , lookup
Sociality and disease transmission wikipedia , lookup
Gluten immunochemistry wikipedia , lookup
Immunocontraception wikipedia , lookup
Complement system wikipedia , lookup
Herd immunity wikipedia , lookup
Monoclonal antibody wikipedia , lookup
DNA vaccination wikipedia , lookup
Lymphopoiesis wikipedia , lookup
Sjögren syndrome wikipedia , lookup
Molecular mimicry wikipedia , lookup
Social immunity wikipedia , lookup
Hygiene hypothesis wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Immune system wikipedia , lookup
Adoptive cell transfer wikipedia , lookup
Polyclonal B cell response wikipedia , lookup
Adaptive immune system wikipedia , lookup
Innate immune system wikipedia , lookup
An Introduction to Modeling the Immune System School of Computer and Communication Sciences EPFL, SS 2007-08 http://swis.epfl.ch/teaching/modeling_immune_system/ Master “Modelling the immune system” Aims The aims of this Master course are: Understand the immune system in order to model it Acquire knowledge about the tools required to model the immune system Review how the models can be used, what types of questions can be addressed, and what technical problems are encountered. Forster collaboration between the modelers and the biologists. Master “Modelling the immune system” Staff The lecturers ¾ Immunologists: Nathalie Debard Jean-Pierre Kraehenbuhl HSeT HSeT ¾ Modelers: Alcherio Martinoli (Jean-Yves Le Boudec EPFL EPFL; sabbatical) Teaching assistant Irina Baltcheva EPFL Master Course outline mmunology Part I: the Immune System ( weeks 1 to 7) (ND,JPK) Tool box Date Teacher Cours Online activity 20 Feb JPK Basic concepts in Immunology none 27 Feb JPK Innate Immunity Exercises: introduction 05 March JPK/ND 12 March JPK Antigen presentation none 19 March JPK T cell immunity none 02 April JPK B cell immunity Article-Based Learning: introduction 09 April JPK/ND Students’ presentations Students’ presentations Part II: modeling toolbox (weeks 8 to 11) (AM, IB) ¾ You already know most of them ¾ The necessary background will be reviewed Non-spatial, macroscopic deterministic models Non-spatial, macroscopic stochastic models Microscopic and spatial models ¾ Simulation issues ¾ Article-based learning Master Course outline Case studies Part III: Case Studies (weeks 12 to 14) Evaluation ¾ Short introduction ¾ Student seminar: ¾ You chose one paper, study it, re-implement the results in a critical fashion, submit a report, and final defense ¾ You will review the work of another team (report and defense) ¾ Teams of 1 or 2 students (recommended) Evaluation ¾ Course project (40%) + oral exam (60%) ¾ Course project: 40% report, 40% defense, 20% review ¾ Assisted exercises during the semester not graded (dry-run exercises for course project and oral exam) Why Modeling the Immune System ? Aims The Immune System provides protection against microbes and cancer cells & allows individual to survive in a hostile microbe-rich environment The immune system is a complex, networked, multi-component system What is Modeling ? Apply mathematical and computational methods to understand the behavior of a complex interaction To do a good modeling study you need to both ¾ Master mathematical and computational methods ¾ Understand the system you are modeling A note on Web Sites Main Support Support http://swis.epfl.ch/teaching/modeling_immune_system/ ¾ Public visibility and material (course presentation, lectures, assignments) ¾ Entry point for student area (moodle) ¾ Archive of past editions (not ready yet) http://moodle.epfl.ch/course/view.php?id=229 ¾ Moodle ¾ Modeling and biology assignments; upload, download files ¾ Forums: exercises/projects; general announcements ¾ Initial access: course key ¾ Further access: usual gaspar login http://epfl.bio-med.ch/ ¾ Immunology Online ¾ E-learning of immunology ¾ Protected, full access via login request (different from gaspar) ¾ Unprotected, partial access via assignment hyperlinks in moodle Defence against infection Three lines of defence Epithelial barrier First line of defense Second line of defense nnate mmunity Adaptive mmunity Invertebrates & vertebrates are continuously exposed to microbes Some microbes are beneficial for their host, other use strategies to establish their niches that are deleterious to the host. Defence mechanisms protect the host: ¾ the first and second lines of defence (epithelial barriers and innate immunity are common to invertebrates and vertebrates ¾ the third line (adaptive immunity) is specific to vertebrates Third line of defense First line of defence: the epithelial barriers Epithelial barriers All body surfaces in contact with the environment are covered by epithelial tissues Epithelial tissues are made of cells that separate 2 compartments Epithelial tissues constitute a first line of defense through ¾ physical factors ¾ chemical factors ¾ immunological factors First line of defence: the epithelial barriers Physical barrier Stratified epithelia: ¾ multiple cell layers ¾ rapid cell turn over Simple epithelia: ¾ membrane specialization ¾ mucus secretion ¾ rapid cell turn over First line of defence: the epithelial barriers Chemical barrier lumen Epithelium Microbicidal peptides that disrupt bacterial cell walls: α defensins (Paneth cells) and β defensins (epithelial cells) Lamina propria Proteins that sequester iron and zinc: lactoferrin (goblet cells) Enzymes produced by mucus cells that hydrolyze components of bacteria cell walls: lysozyme, phospholipase A2 Second line of defence: innate immunity Role of the epithelial cells & leukocytes nnate immune responses occur in two sequential steps: ¾ the recognition of the disease-causing agent. ¾ the immediate activation of defensive effector mechanisms to eradicate it. Both events take place at the disease site. The innate immune system is an evolutionary ancient form of host defense that exists throughout the animal kingdom. It consists of : a wide variety of cells ¾ circulating in the blood & scattered in organs Macrophages Mast cells Neutrophils ¾ forming tissues that separate the outside from the inside world molecules produced by innate immune cells or the liver. ¾ acute phase proteins ¾ complement ¾ cytokines & chemokines The complement ¾ Disruption of microbes by osmotic cell lysis Killing ¾ Opsonization: coating microbes with complement and clearance by phagocytosis ¾ vascular changes (dilatation & increased Recruitment permeability) of killers ¾ chemotaxis (leukocyte attraction) Third line of defence: adaptive immunity Adaptive immunity Features of the adaptive immune system A host defence unique to vertebrates, Important for the survival of individuals over the long term. Mobilizes defences that are adapted to each specific disease-causing agent Retains a “memory” of previous encounters ¾ allows to mount rapid and efficient defences when and if the agent reappears. ¾ increases the likelihood that individuals will survive to reproductive age. The adaptive immune system consists of: ¾ cells called lymphocytes. ¾ molecules that lymphocytes produce, including antibodies "cytokines". ¾ organs called lymphoid organs where lymphocytes divide and reproduce, mature, and perform some of their functions. Lymphocytes migrate in and out of lymphoid organs. Cells & molecules mediating adaptive responses Third line of defence: adaptive immunity T and B lymphocytes ¾ Lymphocytes are the primary cells of the adaptive immune system. ¾ They are formed in primary lymphoid organs in a process called lymphopoiesis. ¾ They express unique surface receptors to detect antigen, in a way that endows each lymphocyte with a structurally unique receptor that recognizes only a particular chemical structure called antigen. Cells & molecules mediating adaptive responses Third line of defence: adaptive immunity T and B lymphocytes Unique features: ¾ Generation of the immune repertoire associated to the naïve lymphocytes ¾ Distribution of the naïve lymphocytes in the secondary lymphoid organs where they encounter antigens ¾ Distribution of the effectors cells where they have to control invading microbes Lymph nodes Spleen MALT Third line of defence: adaptive immunity Cells & molecules mediating adaptive responses molecules ¾ cytokines produced by B and T lymphocytes ¾ antibodies produced by B lymphocytes 2 forms: • membrane bound: receptor • secreted: antibody Structure Function Cells & molecules mediating adaptive responses Third line of defence: adaptive immunity molecules antibodies cytokines ¾promote T cell growth. ¾promote antibody production. ¾activate lymphocytes & macrophages They include: ¾ Interleukins ¾ interferons ¾ chemokines Third line of defence: adaptive immunity The adaptive Mounting an adaptive immune response requires: esponse 1. A recognition phase: recognition of the pathogen or other foreign material by lymphocytes 2. An activation phase, whereby antigen-specific lymphocytes receive a co-stimulatory signal to proliferate and differentiate into effector cells. 3. The clonal expansion of the antigen-specific lymphocytes. 4. The effector phase, during which effector lymphocytes are dispatched to the sites of antigen entry. 5. The contraction phase which occurs following clearance of the antigen. 6. The memory phase, during which surviving cells specific for the priming antigen may persist over long periods of time. Third line of defence: adaptive immunity The adaptive esponse 1. A recognition phase: recognition of the pathogen or other foreign material by lymphocytes Antigen MHC molecules MHC classI MHC classII Third line of defence: adaptive immunity The adaptive Mounting an adaptive immune response esponse requires: Antigen presentation 1. A recognition phase: recognition of the pathogen or other foreign material by lymphocytes Third line of defence: adaptive immunity The adaptive Mounting an adaptive immune response esponse requires: Activation Proliferation 2. An activation phase, whereby antigen-specific lymphocytes receive a co-stimulatory signal to proliferate and differentiate into effector cells. 3. The clonal expansion of the antigen-specific lymphocytes. Third line of defence: adaptive immunity The adaptive Mounting an adaptive immune response esponse requires: 4. The effector phase, during which effector lymphocytes are dispatched to the sites of antigen entry. . Disease-causing agents Bacteria Viruses Protozoa Worms Fungi Lifestyles PAMPs vs antigen Defense against microbes Viral infection Defense against microbes Viral infection Bacterial infection Master “Modelling the immune system” Learning objectives Describe three types of systems that integrate microbial signals and state which innate immune cells instruct the adaptive immune system Compare the innate and adaptive immune systems in terms of cellular components, molecular components and tissue organization. Compare the process of antigen presentation for extra versus intracellular pathogens Explain the difference between PAMPs and antigens. Identify the primary, secondary and tertiary lymphoid tissues and describe their role. Describe the phases associated with the development of both the innate and the adaptive immune responses. Compare innate and adaptive immune responses in terms of immune recognition. Describe which arm of the adaptive immune response is required to protect against extracellular pathogens, in terms of lymphocytes, antigen recognition strategy and defense mechanisms. Home work 1. Study the basic concepts in immunology using the Immunology Online website. 2. Test your knowledge using the quiz. 3. Questions: • Describe three main systems, i.e. epithelium, dendritic cells and resident innate cells, that integrate microbial signals and in which order they operate. • Which immune cells are able to enter an infection site. • How do the innate and adaptive immune systems clear a viral or a bacterial infection.