1MCB 150: MolecularImmunologySpring 2007Prof. Ellen RobeyProf. Robert BeattyProf. Laurent CoscoyToday’s game-plan• Structure of the course and administrativeissues• 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, infection Course 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 highlyrecommended)• Reading: Text (Kuby 6th addition), Journal Articles• Problem sets (posted on web, these are not graded, butare 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 reviewand half focuses on the last third of the class.2Course Web Site• www.mcb.berkeley.edu/courses/mcb150• All lecture notes, problem sets, answers willbe posted for viewing or download• Powerpoint presentations shown in lecturewill 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 4discussion sections.•Problem set/reading material fordiscussion 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 toevade 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-richenvironment of the host.3Some microbes hijack cellular machinery toreplicate and spread. Intracellular pathogensinclude viruses (influenza, HIV) and intracellularbacteria (listeria) and intracellular parasites(malaria, toxoplasma).Listeria bacteria using the actin cytoskeleton ofthe host cell to spread from cell to cell.(Portnoy lab)Toxoplasma parasites (red) and dendritic cells(green) within a mouse lymph node. (Robeylab)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 systemcirculate through the body vialymph and blood. Pathogens andtheir antigens are transported fromtissues via lymphatic vessels tothe lymph nodes where theyencounter immune cells.The cells of the immune systemspend much of their time inlymphoid organs. They develop(arise) in primary lymphoidorgans, and they interact withantigens in secondary lymphoidorgans.Thymus: primary lymphoid organfor T cell developmentBone marrow: primary lymphoidorgan for B cell developmentLymph nodes: collect antigensfrom tissuesSpleen: collects antigens fromblood stream4Overview 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 responseMany different types of blood cells participate inthe immune response to microbes:Innate immune cells: “phagocytes”macrophage, neutrophils, dendritic cellsAdaptive immune cells: “lymphocytes”T cells, B cellsMost blood cellsact to fightinfection.AdaptiveimmunityInnateimmunityBlood cells lineages.Lymphocytes of the adaptive immune systemT helper cells: regulate other immune cellsT cytotoxic (killer) cells: kill infected cellsB cells: produce antibodies (immunoglobulin)Dendritic cells and macrophage: directly kill microbes by phagocytosis and othermechanisms. They also help to activate T cells (connection between innate and adaptiveimmunity)NK cells are lymphocytes that have characteristics of innate and adaptive immunity.Overview 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: innate and adaptiveCytokines and inflammationImmune Effector Mechanisms:Cell-mediated immunity:Phagocytosis (cellular eating)cytotoxcity (cellular killing)Humoral immunity:complement: group of serum proteins that can directly killpathogens.antibodies: (also called immunoglobulin) proteins secretedby B cells that bind directly and specifically to pathogens.Antibodies target pathogens by marking them for destruction byother components of the immune system.5Macrophage fight microbes by engulfing anddigesting them (phagocytosis or cellullar eating).A macrophage engulfing yeastBacteria fight back againstphagocytosisA macrophage attempting toengulf a bacterium Streptococcuspneumoniae, that is covered witha slimy coat.Target cell killing by a cytotoxic (killer) lymphocyteA cytotoxic T lymphocyte (CTL) killing a cellthat has been infected by a virus. NK cells use asimilar mechanism to eliminate tumor cells.Overview of the Immune systemMicrobes: why they are formidable foes.Gross anatomy of the immune systemCells of the immune systemEffector