Pathogens and the immune systemVeronica Leautaud, Ph.D.vl2@ rice.eduKeck Hall 224 / 232-labLecture 8BIOE 301-Bioengineering and World HealthReview of lecture 7• Science– “Science is the human activity of seeking natural explanations for what we observe in the world around us.”• Engineering– Systematic design, production and operation of technical systems to meet practical human needs under specified constraints– Six steps of the engineering design methodInfectious diseases: a global health problem(From Morens, D., et al , 2004)Infectious diseases: a global health problem(MRSA)Infectious diseases: a global health problemInfectious diseases: a global health problemHow can technology help?1. Understanding biology: pathogens & diseaseimmune system2. Developing vaccines: from idea to product- vaccine design-production- testing safety & effectiveness3. Addressing challenges for vaccine development:- Developed vs. developing countries- The AIDS vaccine challenge ScienceEngineeringLecture map1. The players:Types of pathogens Cells of the Immune system2. Types of Immunity2A. Physical barriers2B. Innate Immunity2C. Adaptive ImmunityMacrophagesNeutrophilsComplement proteinsB-lymphocytes: ANTIBODIEST-lymphocytes: Cell-mediatedImmunologic MEMORYSplinter exampleLecture map1. The players:Types of pathogensCells of the Immune system2. Types of Immunity2A. Physical barriers2B. Innate Immunity2C. Adaptive ImmunityMacrophagesNeutrophilsComplement proteinsB-lymphocytes: ANTIBODIEST-lymphocytes: Cell-mediatedImmunologic MEMORYSplinter exampleTypes of pathogensBacteriaMycobacterium tuberculosis Staphylococus aureusEscherichia coli O147:H7Vibrio cholera Bordetella pertussis (whooping cough)VirusesSARS- Severe Acute Respiratory SyndromeInfluenza (Flu)HIV (AIDS)Hepatitis C virusEbola/ Marburg virusesParasitesPlasmodium sp. (Malaria)CryptospridiumCandida albicansFungiBacteriaDNA- Cells with membrane and cell wall (usually)- Can survive & reproduce outside host- Can be killed or inhibited by antibiotics- Responsible for >90% of hospital infectionsSize ~ 1 μmHow do bacteria cause disease?-Invade host-Reproduce- Produce toxins which disturb function of normal cellsParalyze cilia & inhibit clearance of respiratory secretions= whooping coughpertussisHow do bacteria cause disease?MRSA: Methycillin Resistant Staphylococcus aureushttp://www.npr.org/templates/story/story.php?storyId=15453093Viruses Nucleic acid core surrounded by protein capsid, and for some viruses an envelope Use host intracellular machinery to reproduce They cannot be killed with antibiotics, but antivirals may inhibit different stages of their life cycle in the host >50 viruses that can infect humansSize ~ 0.1 μm = 100nmHow do viruses cause disease?1. Virus invades host cell- Binds to cell membrane receptors- Endocytosis brings virus into cell2. Virus takes over cell- Use viral nucleic acid and host cell resources to make new viral nucleic acid and proteins3. More virus is released from host cell- Virus causes host cell to lyse OR- Viral particles bud from host cell surfaceHow do viruses cause disease?The Human Immunodeficiency virus (HIV)SpikesViral components:-nucleic acid core (DNA/RNA)-protein capsid-envelope-GlycoproteinsThe Human Immunodeficiency virus (HIV)How are we protected against pathogens?Lecture map1. The players:Types of pathogensCells of the Immune system2. Types of Immunity2A. Physical barriers2B. Innate Immunity2C. Adaptive ImmunityMacrophagesNeutrophilsComplement proteinsB-lymphocytes: ANTIBODIEST-lymphocytes: Cell-mediatedImmunologic MEMORYSplinter exampleCells of the immune systemBone marrowBlood= plasma + cellsCells of the immune systemBone marrowBlood= plasma + cellsO2& CO2transportClottingWhite Blood Cells (WBC)(T/B)MacrophagesCells of the immune systemBone marrowBlood= plasma + cellsPhagocytosis- ‘eating pathogens’Innate ImmunityMacrophagesDefense vs. parasitesAllergic reactionsB-lymphoctesT-lymphocytesNatural Killer CellsAntibody productionPathogen killingAdaptive ImmunityCells of the immune systemNeutrophil Macrophage LymphocytePhagocytosis- killingB-lymphocytesT lymphocytesNK cellsQuestion:• Based on your understanding of the characteristics of bacteria, viruses, and blood cells, identify which item best represents a bacterium, a virus and a blood cell and be able to explain why you chose each.Lecture map1. The players:Types of pathogensCells of the Immune system2. Types of Immunity2A. Physical barriers2B. Innate Immunity2C. Adaptive ImmunityMacrophagesNeutrophilsComplement proteinsB-lymphocytes: ANTIBODIEST-lymphocytes: Cell-mediatedImmunologic MEMORYSplinter exampleTypes of ImmunityPhysical Barriers-skin(2 square meters!)- mucose membranes (400 square meters!)Innate Immune System- General inflammatory response against pathogens outside of the cellAdaptive Immune System- Can adapt to defend against any specific invader inside or outside of the cell- Important when innate immunity cannot defend against the attack-Provides ‘Immune Memory’What happens when you get a splinter?What happens when you get a splinter?• Pathogen makes it past a physical barrier•Symptoms?– Red, swollen, hot, pus• What causes these symptoms?– The Innate immune system is kicking into gear!• Usually innate immune system can take care of itThe Innate Immune System: 3 main weapons-Activated MacrophagesPhagocyte (‘eat’) invading pathogensProduce chemicals that: - increase blood flow (redness & heat)- cause ‘fuild leaking’ (swelling)- recruit neutrophils (pus)Present antigen to adaptive immune system-Complement proteinsPresent in tissue and bloodAttach to surface of bacteria and viruses targeting them for phagocytosisRecruit other immune cells from bloodWhat happens when you get a splinter?Macrophage attacking E.coli SEM x 8,800 ©Denis KunkelQuestion:• Based on your understanding of the innate immune system, represent a macrophage during phagocytosisLecture map1. The players:Types of pathogensCells of the Immune system2. Types of Immunity2A. Physical barriers2B. Innate Immunity2C. Adaptive ImmunityMacrophagesNeutrophilsComplement proteinsB-lymphocytes: ANTIBODIEST-lymphocytes: Cell-mediatedImmunologic MEMORYSplinter example Recognizes antigens (molecular signatures) specific for each pathogen Effective against both intra- and extracellularpathogens Two main components:The Adaptive Immune SystemHumoral immunity- Relies on
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