Transcript
- Slide 1
- Biology 260: Review for Final
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- Microorganisms Bacteria: unicellular prokaryotic organisms; extremely diverse, adapted to essentially all habitats Fungi: unicellular or multicellular eukaryotic organisms Protozoa: unicellular eukaryotic organisms Algae: unicellular or multicellular eukaryotic organisms
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- Viruses Protein coat = capsid + nucleic acid DNA (ds or ss) or RNA (ss) Not living organisms Not a true cell No cell membrane Enveloped viruses have a stolen membrane that they acquire when budding out of an infected cell No nucleus
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- Cell typeCell wall? Cell membrane? BacteriaProkaryoticYes FungiEukaryoticYes ProtozoaEukaryoticNoYes AlgaeEukaryoticYes
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- Cell typeDNAOrganellesNucleus Cell membrane Ribosomes Prokaryotic Double stranded No Yes 70s (50s + 30s) EukaryoticDouble stranded Yes 80s (60s + 40s)
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- Bacterial Structures
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- Cell Wall Gram-positive Thick layer of peptidoglycan Teichoic acids
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- Cell Wall Gram-negative Thin layer of peptidoglycan Outer membrane - additional membrane barrier Lipopolysaccharide (LPS) O antigen Core polysaccharide Lipid A
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- Cytoplasmic membrane Defines the boundary of the cell Transport proteins function as selective gates (selectively permeable) Control entrance/expulsion of antimicrobial drugs Receptors provide a sensor system Semi-permeable; excludes all but water, gases, and some small hydrophobic molecules Phospholipid bilayer, embedded with proteins Fluid mosaic model
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- Electron transport chain - Series of proteins that eject protons from the cell, creating an electrochemical gradient Proton motive force is used to fuel: Synthesis of ATP (the cells energy currency) Rotation of flagella (motility) One form of active transport across the membrane Cytoplasmic membrane Electron transport chain
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- Internal structures: Ribosomes
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- Unique molecules in bacteria can be used as targets for chemotherapy Cell wall: peptidoglycan, techoic acid Ribosomes Unique biosynthetic pathways
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- Bacterial growth & metabolism Binary fission Growth = increase in # Generation time: time it takes to double the population Pathogens with a short generation time cause rapidly progressive disease (i.e. Vibrio cholera) Pathogens with a long generation time cause chronic, slowly progressive disease (i.e. Mycobacterium tuberculosis)
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- Growth = increase in # Many of our drugs are most effective against growing bacteria Interrupt cell wall synthesis Interrupt/block replication Interrupt/block translation Interfere with biosynthetic pathways
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- Primary and Secondary metabolites
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- Requirements for bacterial growth Environmental factors that influence Temperature, pH, osmotic pressure, oxygen Nutritional factors Carbon, nitrogen, sulfur, and phosphorous Trace elements: iron
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- Chemical control: choosing the right germicidal chemical What is your goal? What type or organism are you targeting? What environment are you treating? sterility vs. disinfection; level of disinfection required dictates potency of chemical required Toxicity: risk-benefit analysis Activity in presence of organic material: most are diminished or inactivated Sensitivity of the material to be treated Residue: toxic or corrosive vs residual desired antimicrobial effect Cost and availability Storage and stability: concentrate vs stock solution Environmental risk: antimicrobials in the environment
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- Innate immune system 1 st line defenses: skin, mucosal barriers, secretions - antimicrobials (lysozyme), iron- binding proteins (transferrin) Complement system Granulocytes (neutrophils, eosinophils, mast cells), monocytes/macrophages, dendritic cells
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- Antimicrobial substances Produced by animals: Lysozyme Peroxidase enzymes Lactoferrin Transferrin Defensins Produced by your microbiota: Fatty acids Colicins Lactic acid
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- Immune Defenses Sensory systems: Pattern recognition receptors Toll-like receptors NOD-like receptors RIG-like receptors Complement system Alternative pathway Classical pathway Lectin pathway
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- The Complement System Central feature = splitting of C3 C3a & C3b Enzyme that splits C3 = C3 convertase C3 also spontaneously degenerates to form C3a & C3b at a constant rate Alternative pathway: C3b binds to foreign cell surface receptors formation of C3 convertase Lectin pathway: pattern recognition receptors = mannose binding lectins (MBLs): bind to mannose molecules on microbial surface formation of C3 convertase Classical pathway: antibody binds antigen = antigen-antibody complex formation of C3 convertase (adaptive immune response)
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- Leukocytes Phagocytes: macrophages & neutrophils Antigen presenting cells Natural killer cells
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- The Acute Inflammatory Response Calor = heat: increased blood flow to site Rumor = redness: increased blood flow Tumor = swelling: fluid and cells accumulate Dolor = pain: pressure + chemical mediators Functio laesa = loss of function: many possible causes...
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- The acute inflammatory response
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- Leukocytes have to get out of the blood vessels: recruitment
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- The Adaptive Immune Response Primary response Secondary response Humoral immunity: B cells, plasma cells, antibodies: target extracellular pathogens Cell-mediated immunity T cells, dendritic cells antigen is inside a cell
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- Overview of the Adaptive Immune Response
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- Lymphocytes CD4 = T helper lymphocytes Activate B cells, macrophages and cytotoxic T cells Memory T cells CD8 = Cytotoxic T lymphocytes B cells Nave Activated Mature = plasma cell (no longer a dividing cell) Memory B cells
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- How are B cells activated?
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- What can happen when antibody binds antigen?
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- MHC MHC class II molecules Expressed by antigen-presenting cells Used to present exogenous (non-self) antigen MHC class I molecules Expressed on the surface of all cells Used to present endogenous (self) antigen Allows recognition and elimination of infected cells viruses, intracellular bacteria
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- Helper T cells recognize MHC Class II
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- Cytotoxic T cells recognize MHC Class I markers
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- What determines outcome of infection? Host defenses: functional immune system? Age? Predisposing infection or other disease? Injury? Pathogenicity of organism virulence factors; evasion or invasion tactics? Infectious dose very large numbers of an organism that is not very virulent will still be able to establish infection; some organisms are so virulent that only a few organisms are required to establish an infection
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- Colonization 2 possible outcomes: Symbiosis Infection Infection: Subclinical vs infectious disease Primary vs secondary infection Opportunist vs primary pathogen
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- Establishing infection Adherence Pili, capsules, cell wall components binding to receptors on host cells Colonization Compete for iron, nutrients Resist opsonization Resist residents antimicrobials Secretion systems
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- Exploitation of antigen sampling processes
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- Avoiding host defenses Hide in cells Avoid complement- mediated killing Avoid phagocytosis Survive in phagocytes Avoid antibodies
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- Disease: damage to host Damage caused by bacterial exotoxins Proteins synthesized by bacteria Highly specific interactions with host cells Highly immunogenic Toxoids Antitoxin
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- Diseases caused by exotoxins Neurotoxins Botulism Tetanus Entereotoxins Cholera Travelers diarrhea Cytotoxins Anthrax Pertussus (whooping cough) Diptheria Hemolytic uremic syndrome Dystentery Membrane-damaging toxins: Gas gangrene Strep throat Abscesses Superantigens Some foodborne intoxications Toxic shock syndromes
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- Cholera Etiologic agent: Vibrio cholerae Toxin: cholera toxin Toxin type: A-B toxin Cell type with receptor: human enterocytes
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- Mechanisms of antimicrobial drugs Inhibition of cell wall synthesis Inhibition of protein synthesis Inhibition of nucleic acid synthesis Inhibition of biosynthetic pathways Disruption of cell membrane integrity
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- Mechanisms of acquired drug resistance Destruction or inactivation of the drug: drug inactivation enzymes Alteration of target molecule (mutation) Decreased uptake: alteration of porins Increased elimination: efflux pumps
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- Acquiring resistance Spontaneous mutation Gene transfer R plasmids
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- Genetics review Replication: duplication of the genome prior to cell division Gene expression: decoding of DNA in order to synthesize gene products (proteins): Transcription: DNA RNA Translation: RNA protein
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- Enzymes necessary for DNA replication Primase: synthesizes the RNA primer DNA Polymerase: synthesize 53 DNA gyrase: releases tension during uncoiling of circular DNA **target of quinolones and aminocoumarins** DNA ligase: seals the gaps between Okazaki fragments (forms covalent bonds) Helicase: unzips 2 strands of DNA
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- ESBL producers are resistant to all - lactam drugs: Penicillins Cephalosporins Carbapenems Vancomycin Bacitracin
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- Emerging drug resistance MRSA: Methicillin-resistant Staphylococcus aureus Drug-resistant Mycobacterium tuberculosis ESBL producers (enterobacteria, enterococccus) Vancomycin-resistant enterococcus
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- Antimicrobial resistance & antimicrobial stewardship Remember the 4 Ds: Right Drug Right Dose De-escalation to pathogen-targeted therapy Right Duration
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- Vectors biological vector a vector in whose body the infecting organism develops or multiplies before becoming infective to the recipient individual. mechanical vector a vector which transmits an infective organism from one host to another but which is not essential to the life cycle of the parasite.
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- But remember: The vast majority of microorganisms do not cause disease We depend on our relationships with microorganisms for many things
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- Normal microbiota Protection Training of the immune system Fermentation: beer, wine, cheese, yoghurt, bread, pickled foods