MCB 150: Molecular ImmunologyToday’s game-planMCB 150 Spring 2007Course InstructorsCourse ComponentsGradingCourse Web SiteGetting Help!!!PowerPoint PresentationOverview of the Immune systemMicrobes are ubiquitous in nature, extraordinarily diverse, rapidly evolve to exploit opportunities to infect hosts and to evade their immune systems.Slide 12Some microbes hijack cellular machinery to replicate and spread. Intracellular pathogens include viruses (influenza, HIV) and intracellular bacteria (listeria) and intracellular parasites (malaria, toxoplasma).Slide 14Slide 15Slide 16The cells of the immune system circulate through the body via lymph and blood. Pathogens and their antigens are transported from tissues via lymphatic vessels to the lymph nodes where they encounter immune cells.Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Bacteria fight back against phagocytosisSlide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Inflammation: a complex series of events induced by tissue damage (described in medical literature in 1500s)Inflammation occurs when injured tissues release mediators that promote vasodialation (increased blood flow) and chemotaxis (directed migration) of leukocytes.Inflammation causes blood cells to move from blood stream to site of injuryBlood cells (leukocytes) travel from the blood stream into tissues by a process known as extravasationBlood cells can also be attracted to sites of infection by products produced by pathogens, as well as by chemoattractants made by host (chemokines, inflammatory meditators).Slide 39Slide 40Diseases associated with immune system dysfunctionMyasthenia gravisAsthma & AllergyTherapeuticsVaccination: THE major successTreating cancerTissue TransplantationPowerful methods for detecting and quantitating proteins and cells based on the highly specific binding of antibodies (immunoglobulins)Western BlotImmunofluoresenceFlow Cytometry: Quantitative Single-cell ImmunofluoresenceInnate (natural) immunitySlide 53Slide 54Physical & Biochemical barriersSlide 56DefensinsSlide 58Slide 59Slide 60Slide 61Slide 62Slide 63Apoptosis: Cellular SuicideApoptosis versus NecrosisSlide 66Slide 67Protein Kinase R: Interfering with InfectionSlide 69Slide 70MCB 150: Molecular ImmunologySpring 2007Prof. Ellen RobeyProf. Robert BeattyProf. Laurent CoscoyToday’s game-plan•Structure of the course and administrative issues •Overview of the immune system•Begin: Innate ImmunityMCB 150 Spring 2007Innate Immunity Humoral ImmunityB cells, antibody, complementPhagocytes, Toll-like receptorsCellular ImmunityT cells, TCR, development, selection, tolerance, NK cellsImmune Responsesinflammation, allergy, autoimmunity, infectionCourse InstructorsLecturers:Ellen Robey471 LSA 2-8669Office hours: Tues 11-12Laurent Coscoy451 LSA 3-4128Office hours: TBARobert Beatty176 LSA 2-0671Office hours: Tues 3-4 GSIs:Dina [email protected] hours: TBATim [email protected] hours: TBACourse Components•Lecture series•Discussion sections (not required, but highly recommended)•Reading: Text (Kuby 6th addition), Journal Articles•Problem sets (posted on web, these are not graded, but are to help reinforce what you learn in class)•Exams-- two mid-terms, plus final examGrading•Mid-terms: 25% each•Final 50%Half of the material final is a cumulative review and half focuses on the last third of the class.Course Web Site•www.mcb.berkeley.edu/courses/mcb150•All lecture notes, problem sets, answers will be posted for viewing or download•Powerpoint presentations shown in lecture will be posted for your reviewGetting Help!!!•Web site: www.mcb.berkeley.edu/courses/mcb150•Discussion groups / GSIs•Office Hours•After lecture-- very brief questions only•No Discussion sections this week. •Sign up sheets available in class today•You may attend any or all of the 4 discussion sections.•Problem set/reading material for discussion will be posted on websiteOverview of the Immune systemMicrobes: why they are formidable foes. Gross anatomy of the immune systemCells of the immune systemEffector mechanisms: how the immune system protectsImmune recognition of pathogens: innate vs adaptive immunityCytokines and the inflammatory responseMicrobes are ubiquitous in nature, extraordinarily diverse, rapidly evolve to exploit opportunities to infect hosts and to evade their immune systems.Exponential Growth1101001000100001000001000000100000001000000001 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25Time (minutes/10)# of bacteria8 hours = 280 trillion bacteria!!!!Exponential growthNumber of bacteriaTime (hrs)Many pathogens can expand rapidly in the nutrient-rich environment of the host.Some microbes hijack cellular machinery to replicate and spread. Intracellular pathogens include viruses (influenza, HIV) and intracellular bacteria (listeria) and intracellular parasites (malaria, toxoplasma).Listeria bacteria using the actin cytoskeleton of the host cell to spread from cell to cell. (Portnoy lab)Toxoplasma parasites (red) and dendritic cells (green) within a mouse lymph node. (Robey lab)Pathogens rapidly evolve to avoid the host immune responseVirally encoded decoy receptorsOverview of the Immune systemMicrobes: why they are formidable foes. Gross anatomy of the immune systemCells of the immune systemEffector mechanisms: how the immune system protectsImmune recognition of pathogens: innate vs adaptive immunityCytokines and the inflammatory responseFirst some key definitions:Pathogen: microbe that causes diseaseAntigen: material (from a pathogen) that induces an immune responseInnate (natural) immunity: rapid, non specific immune responseAdaptive (acquired) immunity: slower, specific immune responseLeukocytes: blood cellsLymphocytes: specialized blood cells that mediate adaptive immunity (e.g. T and B cells)The cells of the immune system circulate through the body via lymph and blood. Pathogens and their antigens are transported from tissues via lymphatic vessels to the lymph nodes where they encounter immune cells.The cells of the immune system spend much of their time in lymphoid organs. They develop (arise) in primary lymphoid organs, and they interact with antigens in secondary lymphoid organs.Thymus: primary lymphoid organ for T cell developmentBone marrow: primary lymphoid organ for B cell developmentLymph nodes: collect antigens from tissuesSpleen: collects antigens from blood streamOverview of the