Microorganisms and Disease
MICR 3230
1998
These notes are provided for you to key on particular topics covered in class. Lecture notes and your book will be more detailed.
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Chapter 1
Cell theory - Robert Hooke Pneumonia - Legionella pneumophila Toxic shock syndrome - Staphylococcus aureus Anthrax - Bacillus anthracis Smallpox - Smallpox virus; Pustula Anton van Leeuwenhoek - Animalcules Francesco Redi - Spontaneous generation opponent John Needham - Spontaneous generation proponent Spallanzani - Spontaneous generation opponent Rudolf Virchow - Theory of Biogenesis Louis Pasteur - Fermentation, Pasteurization; Attenuation; Spontaneous generation opponent Ignaz Semmelweis - Cross-contamination of patients by physicians Joseph Lister - Infection control in hospitals Robert Koch - Koch's Postulates; Bacillus anthracis Edward Jenner - Vaccination; Smallpox virus Paul Ehrlich - Salvarsan; Chemotherapy Alexander Fleming - Penicillium notatum; Antibiotic; Penicillin See Penicillin
Synthetic drugs - Chemotherapy Iwanowski - Filterable virus Stanley - Crystallized virus Avery - DNA is hereditary material Watson and Crick - DNA structure and DNA replication Jacob and Monod - Discovered mRNA and regulation of genes Genus - First name of scientific name Specific epithet - Second of scientific name Species - Genus and specific epithet Staphylo - Clustered arrangement Coccus - Shaped like spheres Prokaryote - Eubacteria and Archaeobacteria Protista - Slime molds, protozoans, and some algae Fungi - Unicellular yeasts, multicellular molds, mushrooms
See Yeast Cells (Go to yeasts and molds at the bottom of the site and click on yeast)
Plantae - Some algae, mosses, ferns, conifers, flowering plants Animalia - sponges, worms, insects, vertebrates Bacillus - Rodlike Coccus - Spherical or ovoid Spiral - Corkscrew Prokaryote - Bacteria, no nuclear membrane Cell walls - Peptidoglycan Binary fission - reproduction method for bacteria Nutrition for bacteria - Organic chemicals; photosynthesis; inorganic chemicals, dead organic, living host Flagella - Appendage used by bacteria for locomotion
Eukaryote - Nucleus, nuclear membrane Normal flora - Normal microbiota; microorganisms that colonize an animal without causing disease. Usually benefit the host. Resistance - Barriers to invasive tactics of potential pathogens; Barriers may be anatomical (skin) or chemical, low pH of the stomach. Infectious disease - Disease caused by an infectious agent (pathogen). Susceptible host is invaded. The pathogen may carry part of its life cycle in the host.
See Infectious Disease
Eradication of infectious agents - Plasmodium vivax and malaria; vaccine against diphtheria and resurfacing from the USSR are examples. Emerging Infectious Diseases - Mad cow disease; Bovine spongiform encephalopathy; infection caused by a prion. Prion - Infections protein.
See Prion
Creutzfeldt-Jakob Disease - Disease in humans caused by a prion. E. coli - Strain O157:H7 causes a bloody diarrhea when it grows in the intestines; contaminated food such as hamburgers. Invasive group A Streptococcus - Flesh eating bacteria. Ebola hemorrhagic fever - Ebola virus in Zaire; epidemic among hospital workers. Hantavirus - Virus from deermouse droppings. Epidemic in the Four-Corners area. AIDS - HIV attacks CD4+ T cells (T helper cells).
Chapter 3 1 nm - 10-9 m; 10-3 mm; 10-6 mm
See How Big
See Scale
Compound microscope - Two sets of lenses, objective, ocular Low power magnification - 10 X 10 High power magnification - 10 X 40 Oil immersion - 10 X 100 Brightfield - Specimen is brightly illuminated. Darkfield - Specimen appears light against a dark background. Fluorescence microscopy - Ultra violet light; FITC; fluorescence dye; antibody. Electron microscope - Beam of electrons, electromagnetic lens, scanning, transmission.
See Transmission Electron Microscopy
See Transmission Electron Microscope
See Scanning Electron Microscopy
Smear - Thin film of material with microorganisms. Fix - Attachment of microbes to surface, heat Stain - Salt composed of positive and negative ion in solution. Basic stain - Positive ion is the chromophore, crystal violet, methylene blue, safranin, stains bacteria. Acidic stain - Negative ion is the chromophore, eosin, nigrosin, stains the background. Negative staining - Bacteria colorless, background is stained, distortion minimized Simple stain - Highlights microorganism, shows some structures in bacteria, crystal violet, methylene blue, and other stains. Mordant - A chemical that enhances bacterial staining, iodine for example. Differential - Stain that reacts differently with different bacteria; can be used to distinguish among bacteria Gram stain - Differential staining method, divides bacteria into two large groups Decolorizing agent - Used in the Gram staining method, ethanol, ethanol-acetone, removes primary stain from cells of some species Counterstain - Stains that have a contrasting color to the primary stain in the Gram staining method, e.g. safranin. Gram-positive - Bacteria that retain color (purple) after washing with ethanol, tend to be easily killed by penicillin and sulfanamides. Gram-negative - Bacteria that lose color (purple) after washing with ethanol, are more susceptible to streptomycin, chloramphenicol, and tetracycline Acid-fast - Differential staining method, used to identify Mycobacteria and Nocardia, groups that contain a waxy material in their cell walls. Acid-fast procedure - Fixed smear, carbolfuchsin, heat, cool, wash, decolorizer (acid-alcohol), methylene blue (counterstain). Acid-fast = red; non-acid-fast = blue. Mycobacterium tuberculosis - Acid-fast, causes tuberculosis. Mycobacterium leparae - Acid-fast, causes leprosy. Special stain - Color specific parts of microorganisms. Capsule - Gelatinous covering around many microorganisms, soluble in water, dislodged during washing, not stained with biological stains, adds to virulence of pathogens. Virulence - Degree to which a pathogen can cause disease. India ink - Negative staining for capsules, provides background. Endospore - Protects microbes from adverse conditions, highly refractive, few pathogens have spores. Schaeffer-Fulton stain - Spore stain. Schaeffer-Fulton staining method - Fixed smear, malachite green, heat to steaming for 5 min, wash, counterstain with safranin. Endospore = green, cells = red Flagella - Structures for locomotion, mordant and stain increases the diameter of flagella to see with light microscope; -Monotrichous - Single polar flagellum. -Lophotrichous - Two or more flagella at one pole of the cell. -Amphitrichous - Single flagella at both ends of the cell. -Peritrichous - Flagella distributed over the entire cell. -Structure - Filament, hook, basal body, flagellin.
See Flagella
See Motility
Taxis - Movement toward or away from a particular stimulus. -Chemotaxis - The stimulus is chemical. -Phototaxis - The stimulus is light.
Chapter 4 Procaryote, Eucaryotes - Living cells; composed of nucleic acids, proteins, lipids, carbohydrates; use similar chemical reactions to metabolize food, build proteins, and store energy. Procaryote - DNA is not enclosed within a membrane; lacks other membrane-bound organelles, DNA is not associated with histones; peptidoglycan walls, division by binary fission. Virus - Non-cellular elements with cell-like properties. Glycocalyx - Substances that surround bacterial cells, capsule, slime layer. Capsule - Organized glycocalyx; Streptococcus pneumoniae, Bacillus anthracis, Klebsiella pneumonia; increases virulence. Slime layer - Unorganized glycocalyx. Corynbacterium - Pleomorphic. Spirochete - Spiral microorganism; move by means of axial filament. Fimbriae and Pili - Hairlike appandage, pilin. -Fimbriae - Allows cells to adhere to surfaces including other cells -Neisseria gonorrhea - Causative agent of gonorrhea; if it has fimbriae it can attach to mucous membranes and cause disease. -Pili - Joins bacterial cells prior to transfer of DNA from one cell to another; also called sex pili. b1,4 linkage - Linkage between C1 and C4 of two sugar molecules that are in a b rotation.
See Cell Wall
See Penicillin2
Lysozyme - Enzyme that attacks the b1,4 linkage between NAG and NAM; found in tears, phagocytes, intestinal tract, urogenital tract. Klebsiella pneumonia - May form capsules. Bacillus anthracis - May form capsules. Streptococcus pneumonia - May form capsules. N-acetylglucosamine - NAG; one of the two sugars that makes up the disaccharide of peptidoglycan N-acetylmuramic acid -NAM; one of the two sugars that makes up the disaccharide of peptidoglycan; has a tetrapeptide side chain; may be crosslinked with an amino acid bridge. G+ bacteria - Several layers of peptidoglycan; attacked easily by lysozyme; many contain teichoic acids. G- bacteria - Small amounts of peptidoglycan; not easily attacked by lysozyme; no teichoic acids; outer membrane (lipoprotein, lipopolysaccharde, phospholipid), middle peptidoglycan layer in the periplasmic space (periplasmic gel), which is followed by a plasma membrane. Teichoic acid - Molecule composed of alcohol and phosphate; glycerol and ribitol are examples; may bind and regulate movement of cations into and out of cell, regulates activities of autolysins, store for phosphate Acid-fact bacteria - Contain petidoglycan, but up to 60% of the wall is lipid Mycolic acid - Lipid in Acid-fast bacteria. Outer membrane of G- bacteria - Strong negative charge; evades phagocytosis and action of complement; provides barrier to certain antibiotics, lysozyme, detergents, heavy metals, digestive enzymes, certain dyes.
See Membrane
Porin - Proteins embedded in outer membrane, forms channels Specific channel - Channel in outer membrane; passage of specific substances, e.g. iron, vitamine B12, nucleotides; also attachment site for some viruses and bacteriocins. Lipopolysaccharide - Lipid-sugar complex on cell wall (outer membrane) of G- bacteria; composed of O polysaccharide and Lipid A. O polysaccharide -Functions as antigen; can be used to distinguish G- bacteria, for example O157 is the specific antigen of the pathogenic bacteria that contaminated hamburger meat and caused diarrhea in humans. Lipid A - Endotoxin; toxic in bloodstream; causes fever and maybe shock. Negative charge - Evades phagocytosis and action of complement on outer membrane. Mycoplasma - Smallest known bacteria; can grow and reproduce outside living host cells; plasma membranes have sterols; (some types of eucaryotic cells. i.e. human cells, have cholesterol as a component of their plasma membranes). Sterols - Protect cells from osmotic lysis. L form - Mutated (genes change) bacteria with defective walls. Lysozyme - Hydrolyzes the (1,4 bond between NAG and NAM. Protoplast - Bacteria without a cell wall. Plasma membrane - Composed of phospholipid and protein; eucaryotic cells additionally contain CHO and sterol. Procaryotic plasma membrane - Less rigid because lack sterols. Plasma membrane function - Selectively permeable. Mesosome - Irregular fold of plasma membrane; reproduction and metabolism? Destruction of plasma membrane - Alcohol; quaternary ammonium compounds; polymyxins. Nucleoid - Bacterial chromosome; double-stranded; spherical, elongated or dumbell-shaped; no histones, genetic information. Plasmid - Extrachromosomal genetic element; replicates independently of chromosomal DNA; generally not crucial for survival; may carry R factors or genes for production of toxins. Ribosomes - Site where proteins are synthesized; composed of two subunits, each of rRNA and protein; 50s, 30s, 70s; site of action of streptomycin, neomysin, and tetracycline. Volutin - Metachromatic granule; seen in Corynebacterium diphtheriae. Other granules - Polysaccharide, lipid, sulfur, carboxysomes, gas Endospores - Highly durable dehydrated bodies with thick walls; found in the genus Clostridium and Bacillus.
Chapter 6 Microbial growth - Number of cells, not size; total mass is approximately equal to the number of cells. Psychrophiles - Cold-loving. Mesophiles - Moderate-temperature loving. Thermophiles - Heat-loving. Minimum growth temperature - Lowest temperature at which a particular species will grow. Optimum temperature - Temperature at which the species grows best. Maximum temperature - Highest temperature at which growth is possible. Refrigeration temperature - 4o C; most bacteria grow slowly; most spoliage bacteria will not grow; most pathogenic bacteria will not grow; Staphylococcus aureus remains alive. pH - Most bacteria grow best between pH 6.5 and 7.5. Acidophiles - Bacteria that tolerate acid conditions. Alkaline conditions - Inhibits bacterial growth. Osmotic pressure - Pressure required to prevent the movement of pure water into a solution containing some solute Isotonic solution - A solution in which the overall conc. of the solutes are the same on both sides of a membrane. Hypotonic solution - A medium whose conc of solutes outside the cell is lower than inside the cell. Hypertonic solution - A medium having a higher conc of solutes than the cell. High salt or sugar conc - Draws water out of a bacterial cell; used for food preservation. Halophile - Bacteria that require high salt concentration for growth Falcultative halophiles - Do not require high salt conc, but are able to grow at salt conc. Aerobe - Use molecular O2 as the final electron acceptor in an electron transport chain.(See Chapter 5). Obligate aerobe - Require oxygen to live. Facultative anaerobe - Bacteria that can continue to grow in the absence of oxygen. Obligate anaerobe - Unable to use molecular O2 for energy yeilding reactions; most harmed by molecular O2; cannot use O2 as the final electron acceptor in an eletron transport chain; Pseudomonas and Bacillus can use NO3- as a final electron acceptor, others may use SO42-; Streptococcus uses organic compounds and Clostridium uses inorganic compounds as the final electron acceptor. Use only part of the Krebs Cycle and not all carriers in the electron transport system are used, therefor ATP yield is less and anaerobes tend to grow slower. Flavoprotein - Flavins (vitamin B2) for e.g.; electron transport system. Cytochromes - Iron-containing proteins; electron transport system. Ubiquinones - Non-protein electron carriers; Coenzyme Q for e.g.; electron transport system. Singlet oxygen - Toxic form of oxygen. Superoxide free radicle - Toxic form of oxygen; small amts produced in respiration. Superoxide dismutase - Enzyme produced by most bacteria to neutralize effects of superoxide free radicles. Use to convert superoxide free radicle to molecular O2 and H2O2. Peroxide - Toxic form of oxygen; may be in the form of H2O2 or benzoyl peroxide. Catalase - Enzyme in living things that converts H2O2 to H2O and O2. Hydroxyl free radicle - Toxic form of oxygen. Chemically defined media - A medium in which the exact composition is known. Fastidious - Organisms that require additional growth factors; the more fastidious the harder to grow. Complex media - The chemical composition varies slightly from batch to batch; made up of nutrients such as extracts from yeast, beef, plants, or digests of proteins. Peptones - Partially hydrolyzed proteins; accomplished by partial digestion of proteins with acids or enzymes. Nutrient broth - Complex medium in liquid form. Nutrient agar - Agar added to nutrient broth to solidify. Agar - Complex polysaccharide from marine algae; few microbes can degrade; melts at 100o C; remains in liquid form until temp drops to 40o C; at temp of 50o C will not injure some bacteria. Can make slants (tube at an angle), deeps (verticle tube),or petri dishes (shallow dish with a lid). Reducing media - Media containing a reducing agent to remove O2; e.g. Na thioglycollate chemically combines with dissolved O2 Anaerobic jar - Jar in which O2 is removed, usually by a chemical reaction; Packet contains Na bicarbonate and Na borohydrate; add water and H and CO2 are is released; in the presence of palladium (catalyst), the H2 and O2 combine to form H2O; CO2 also aids in growth of many anaerobic bacteria. Mycobacterium leprae - Leprosy bacteria; usually grown in armadillos Rickettsias, Chlamydia - Obligate intracellular parasites; can reproduce only in living host cells. Candle jar - Jar in which cultures are grown in up to 10% CO2; a candle is lit, then the jar closed; not an anaerobic jar Selective media - Suppresses the growth of unwanted bacteria and enhances the growth of desired bacteria; e.g. bismuth sulfite inhibits Gram positive bacteria and most Gram negative intestinal bacteria; good for isolating Salmonella typhi ; Brilliant green inhibits Gram positive bacteria; used to isolate Gram negative Salmonella Differential media - Used to distinguish colonies of the desired organism from other colonies growing on the same plate; add RBC to agar plates where some produce a clear ring around the colony Streptococcus pyogenes - Causes strept throat; hemolysis RBC in agar plates.
See Streptococcus
Staphylococcus areus - Can use a combination of differential and selective media to identify; tolerates high NaCl and ferments mannitol (red/pink) to form acid (yellow). Enrichment culture - Medium with special nutrients; used when bacteria in small numbers or when bacteria is of an unusual physiological type Colony - Theoretically arises from a single spore or cell; may arise from a clump of cells or cell chain; one colony corresponds toone cell; pure culture if a single colony. Streak plate method for isolation - Sterile loop, streak in one direction on plate, flame loop, streak in a second direction perpendicular to the first streak; flame and streak one time in a perpendicular direction to the second streak. Preservation of bacterial cultures - Short-term - refrigeration -Long-term - -50o C to - 95o C; or lyophilization Generation time - Time required for a cell to divide; population doubles; varies according to species; E. coli has a GT of 20 min. 100,000 - 105 1,000,000 - 106 Lag phase - Time required before bacteria actually start dividing in a growth curve experiment; cells elongate in preparation for division. Log phase - GT reaches a constant minimum; maximum rate of doubling; log plot is a straight line; cells sensitive to adverse conditions, i.e. radiation, antibiotics, etc. Stationary phase - Cell death = new cells produced. Chemostat - Apparatus that removes spent medium and adds fresh medium to a culture Death phase - Log decline; only the most resistant cells survive, e.g. spores Measurement of microbial growth - Cell numbers; total mass. See Bacteria Divide
See Factors Affecting Growth
Plate count - Measures viable cells; takes time; each cell = one colony. Serial dilution - Explain Pour plate method - Add bacterial sample to plate, add nutrient agar and spread by using a circular motion Spread plate method - Nutrient agar is solid medium in plate, apply bacterial sample to plate, spread with a sterile glass rod. Filtration method - Used for concentrating bacteria on a filter before plating. Coliforms - Bacteria from the intestinal tract; indication of fecal contamination. Direct microscopic counts - Breed method; Petroff-Hauser counter; Electronic counters. Turbidity method - Indirect counting method; use a spectrophotometer.
Chapter 7 Sterilization - All forms of life destroyed; moist heat = 121o C for 15 min; dry heat = 170o C for 120 min. Disinfection - Vegetative pathogens destroyed; maybe not spores or viruses; chlorination of water. Antisepsis - Disinfection of living tissue; treatment of wounds. Germacide - Chemical agent kills microbes; maybe not spores; bactericide; fungicide, sporicide; amoebicide; virucide. Bacteriostasis - Bacterial growth inhibited, not killed; referigeration. Asepsis - Absence of pathogens; air filtration. Degerming - Removal of transient microbes; alcohol swab. Sanitation - Reduction of pathogens to safe level. Pseudomonas - Opportunistic pathogen; normally harmless; usually resistant to chemical disinfectant and antiseptics; troublesome in hospitals; become pathogens in absence of normal competitive flora; g-. Mycobacterium - Acid-fast;Non-spore forming, but greater resistance to disinfectants; opportunistic = immune system depressed - organism grows.
See M. bovis (Go to "Microbes and Disease at the bottom of the site and click on Mycobacterium)
Resistance to chemical disinfectants - Endospores; cysts of protozoans; some viruses; chlorine in water. Physiological state of microbe - Actively growing are more susceptible than older cells; actively metabolizing and reproducing = more points of vulnerability; endospore is more resistant than vegetative cells. Environment - Organic matter gives protection; bacteria in cream for e.g.; heat + acid more killing than heat in neutral pH. Plasma membrane - Damage causes cellular contents to leak; ammonium compounds; antibiotics; alcohol Proteins - Damage to 3d shape results in denaturation. Damage to DNA or RNA - Genetic message; radiation; chemicals; replication. Rate of microbial death - Microbes usually die at a constant rate; the more microbes at the beginning of treatment the longer
it will take to kill all.
Physical methods of microbial control - Heat, moist heat, dry heat, filtration, low temperature, desiccation. Heat - Most common method for killing bacteria; most economical; easily controlled; denatures proteins. Moist heat - Boiling; pressure cooker; autoclave; Pasteurization. Boiling - 100o at sea level; 10 min of boiling vegetative forms of bacteria killed; also fungi and their spores; many viruses killed; bacterial endospores are resistant, some up to 20 hrs of boiling; some viruses survive up to 30 min of boiling, can e.g. hepatitis virus; not a reliable method for sterilization; kills most pathogens; makes water and food safe for consumption. Sterilization - Use autoclave; uses moist heat; free flowing steam at 100o C plus 1 atm (15 psi) pressure raises temp to 121o C; 20 psi plus 100o C raises temp to 126o C; all organisms and endospores killed at 121o C in autoclave for 15min; steam must be in contact with the surface of material to be sterilized; air must be evacuated; chemical composition of material is important, e.g. mineral oil vs. water. Pasteurization - High temperature- short time (HTST) 72o C for 15 sec; ultra high temperature (UHT), 74o C to 140o C for 3 sec to 74o C for a total time of 5 sec will kill all bacteria. Dry sterilization - Direct flame; incineration; hot air sterilization Direct flame - Heat to a red glow; 100% effective Incineration - Sterilize and dispose of contaminated cups, bags, dressings Hot air sterilization - Oven at 170o C for 2 hrs Filtration - Passage of liquid or gas through a membrane; pores are smaller than bacteria or virus; membrane filters are cellulose or plastic polymers with pore sizes of 0.22 mm or 0.45 mm down to 0.01 mm. Low temperature - Refrigeration is bacteriostatic; freeze fast to prevent ice crystal formation to preserve . Desiccation - Absence of water; without water no growth; microbes may remain viable for years; add waterrevives microbe; preserve food e.g. jerky; Niesseria gonorrhoeae will die if dried for 1 hr; M. tuberculosis will survivefor months in a dried state; influenced by the environment, e.g. embedded in mucus, pus, feces. Osmotic pressure - High salt or sugar conc gives hypertonic environment; removes water from bacterial cell; molds and yeasts in general are better able to grow in low moisture or high osmotic pressure than bacteria. Radiation - Two types, ionizing and non ionizing. Ionizing radiation - Wavelength < 1 nm; g rays; high energy electron beams; ionizes water form highly reactive hydroxyl radicals. g rays - From cobalt source; high energy; high penetrating ability; need longer exposure High energy electron beams - From accelerator of electrons; lower penetrating ability; shorter exposure needed. Non ionizing radiation - Wavelength between 1 nm and 300 nm; uv light. Uv light - Absorbed best by DNA at 260 nm; forms thymine dimers; inhibits correct replication of DNA; low penetrating power; e.g. paper, and glass; harms eyes. Chemical methods of microbial control - Phenol; phenolics; halogens; alcohols; heavy metals; surface- active agents; quaternary ammonium compounds; organic acids and derivatives; aldehydes; gaseous chemosterilization; oxidizing agents. Phenol - Skin irritant; disagreeable odor; need 1% or higher conc to be effective. o-phenyl phenol - Phenol derivative; reduced irritability; increased antibacterial activity; injures plasma membrane and denatures proteins; main ingredient in Lysol. Hexachloropene - pHisoHex; used widely in soaps and lotions; persists on skin; prolonged use causes neurological damage. Halogens - Iodine; Chlorine; I2 and Cl2 in solution; may use as a constituent of inorganic compounds. Alcohols - 70% ethanol; isopropanol (rubbing alcohol) better than ethanol. Heavy metals - Silver, mercury, copper; metal ions combine with sulfur of - SH group on proteins, i.e. denatures proteins; 1% silver nitrate = eye wash; mercuric chloride = bacteriostatic but may be toxic (mercurochrome, merthiolate);copper sulfate + destroys green algae in swimming pools; zinc chloride = mouth wash. Surface-active agents - Surfactants; decrease surface tension among molecules in a solution; emulsification - break large drop (oil, e.g.) to smaller droplets which are now easier to wash; soaps, detergents are surface-active agents, but generally are not antiseptic, but good for mechanical removal of objects (bacteria) from skin; deodorant soap contains triclocarbon which inhibits g+ bacteria; acid anionic surface agents used in the diary industry. Quaternary ammonium compounds - Quats; Cepacol = mouth wash. Organic acid and derivatives - Preservatives; sorbic acid inhibits mold growth; benzoic acid is an antifungal agent. Aldehydes - Effective anti-microbial agent; formaldehyde; formalin (37% aqueous solution of formaldehyde); glutaraldehyde. Gaseous chemosterilization - Chemicals that sterilize in a closed chamber; do not require heat; ethylene oxide denatures proteins and widely used to sterilize medical supplies and is asuspected carcinogen. Oxidizing agents - Ozone; H2O2; oxidize cellular components of microbes.
Chapter 8 Genes - Units of heredity on DNA; carry information for shape, structural features (morphology), biochemical reaction(metabolism) and ability to move; a segment of DNA that codes for a functional product; functional products include rRNA, tRNA and proteins; genes that code for proteins are called structural genes. Chromosome - Cellular structure; contains DNA. DNA - Macromolecule consisting of repeating units called nucleotides. Nucleotide - Composed of nitrogenous base (adenine, thymine cytosine, guanine), 5 C sugar (deoxyribose) and a phosphate group. Double helix - Conformation of DNA; antiparallel in which the direction of one strand is oriented so that the sugar molecules are all in 5' to 3' mode and the complementary strand is in 3'to 5' mode. Base pairing - Adenine pairs with thymine; cytosine with guanine. See DNA
Genetic language - Four bases: adenine, thymine, cytosine, guanine; possible sequence arrangement of four bases is 44; for 100 it is 4100; for 1000 it is 41000; average length of one gene is 1000 bases long. Genotype - Genetic makeup; information that codes for all the particular characteristics of the organism; collection of genes. Phenotype - The expressed properties, i.e. collection of proteins; enzymes have catalytic properties; structural proteins compose membranes, ribosomes et.al. DNA of bacteria - Single chromosome, circular molecule of DNA that is double stranded; attached at one or more points to plasma membrane. E. coli - Has 4 x 106 base pairs; approximately 1 mm in length; tightly packed, coiled; takes up 10% of the cell's volume. DNA replication - Semiconservative replication; each of two new daughter cells has one new strand from parent and one newly synthesized strand. Replication fork - Point at which replication is occurring; replicatio from 5' to 3'. Leading strand - New DNA strand synthesized continuously from 5' to 3'; uses DNA polymerase and othe enzymes for synthesis. Lagging strand - New DNA strand synthesized discontinuously in fragments of about 1000 nucleotides; synthesized in short strands from 5' to 3'; uses RNA polymerase and a short stretch of RNA nucleotides called RNA primer. Replication proteins - Unwinding enzymes; Stabilizing proteins; DNA polymerase; DNA ligase. Unwinding enzymes - Proteins that are responsible for unwinding the two strands of DNA; required for new synthesis. Stabilizing proteins - Proteins that prevent the unwound DNA strands from rewinding so that new synthesis can occur. DNA polymerase - Enzyme that catalyzes the continuous synthesis of the new DNA strand (leading strand) on the parental DNA template. RNA polymerase - Enzyme that catalyzes the discontinuous synthesis of new DNA (lagging strand) from parental DNA template; reguires DNA ligase. DNA ligase - Enzyme that joins the discontinuous fragments with covalent bonds to make a continuous lagging strand. Rate of replication in E. coli - 1000 nucleotides per sec at 37o C; in log phase have multiple forks; DNA synthesis matches rate at which cell divides. Flow of genetic information - DNA (transcription) --> mRNA (translation) --> protein.
See Central Dogma Kinds of RNA in microbial cells - mRNA; rRNA; tRNA; contain ribose instead of deoxyribose; bases include adenine, uracil (instead of thymine), cytosine, and guanine. mRNA - Codes for proteins. rRNA - Forms an integral part of ribosomes. tRNA - Involved in protein synthesis. Transcription - The synthesis of a complementary strand of RNA from a DNA template; A in DNA dictates U; T dictates A; C dictates G; and G dictates C; e.g. DNA strand of CATTGCAG will dictates an RNA of GUAACGUC sequence; only one DNA strand serves as template; RNA is synthesized from 5' to 3' direction; uses RNA polymerase. RNA polymerase - Enzyme that catalyzes the synthesis of mRNA from one of the DNA strands; binds to DNA at a site called promoter; the endpoint for transcription is a site on DNA called terminator. Promoter - Site on DNA where RNA polymerase binds. Terminator - Site on DNA where RNA polymerase ceases transcribing; both RNA polymerase and mRNA are released at this site. Translation - The process in which mRNA is decoded in an amino acid sequence of a protein; takes place in the cytoplasm. Ribosome - Site of protein synthesis; composed of ribosomal RNA and protein; each ribosome consists of two subunits which come together with mRNA at the start of translation. tRNA - Transfer RNA; amino acids in the cytoplasm are activated and transported by tRNA to mRNA; amino acid activation requires an activating enzyme and ATP for energy. Codon - A set of three nucleotides on mRNA; codes for a single amino acid; the sequence AUGCCAGGCAAA has four codons; AUG is for methionine; CCA for proline; GGC for glycine; and AAA for lysine. Anticodon - Set of three nucleotides complementary to the codon, e.g. AUG (the codon) on mRNA is complementary to UAC (the anticodon) on tRNA.
See Genetic Code
See Protein Synthesis Polyribosome - Several ribosomes together with attached mRNA. Genetic recombination - The exchange of genes between two DNA molecules to form new combinations of genes on a chromosome; cross-over ---> break ----> recombination; in bacteria recombination occurs between two bacteria; contributes to genetic diversity; donor cell (part of DNA)---> recipient cell. Recombinant - Bacterial recipient cell that incorporates donor DNA into its own DNA; genetic transfer is infrequent; about 1% of the population. Transformation - Genes are transferred from one bacterium to another as "naked" DNA in solution; demonstrated by Fredrick Griffith (1928); occurs in a very few genera (Bacillus, Hemophilus, Neisseria, Acinetobactor, Rhizobium, Streptococcus, Staphylococcus); for best results recipient should be in late log phase. Encapsulated bacteria - Streptococcus pneumonia for one; virulent because it is not phagocytosed (kills mice); non-encapsulated is avirulent (does not kill mice); heat-killed virulent (does not kill mice); heat-killed virulent + non-encapsulated (kill mice because the genes for capsule production have been absorbed by the viable, non-encapsulated bacteria giving them the ability to produce capsules). Avery (1944) - Extracted material (DNA) from encapsulated S. pneumoniae and incubated with non-encapsulated S. pneumoniae and produced capsulated S. pneumoniae. Conjugation - Transfer of genes is mediated by plasmids; requires direct cell to cell contact; conjugating cells must be of opposite mating types; donor (+) has plasmid, recipient (-) does not. Plasmid - Circular pieces of DNA that replicate independently of the cell's chromosome; generally plasmids carry genes that are not essential for growth of the cell; may carry R (resistance) factors which can make a bacterium resistant to an antibiotic. F-factor - Extrachromosomal DNA(plasmid) in E. coli; makes a cell +; transfer of a single copy of the F-plasmid to a - cell will make that cell a + cell; the F-factor can recombine (recombination) with the bacterial chromosome; the resulting cell with the integrated F-factor is now called an Hfr (high frequency of recombination) because every time the bacterium replicates, the integrated F-factor also divides; an Hfr can transfer the F-factor along with bacterial chromosomal genes into a recipient; R-factors (resistence) can be transferred. Transduction - Transfer of genes is mediated by a bacteriophage (bacterial virus); sometimes during phage DNA replication, a bacterial gene may get incorporated into the phage DNA. This bacterial DNA (genes) can now be tansferred to other bacteria by the phage and may integrate into the DNA of the infected bacterium.
See Bacterial Genetics
Chapter 10
Five-Kingdom System - Procaryotes (Monera), Protista, Fungi, Plantae, and Anamalia. Three Cell Type groups - Archaea, Eubacteria, Eucaryotes. Scientific Nomenclature - Binomial nomenclature. Rules for classification - International Committee on Systematic Bacteriology
Chapter 11 Bergy's Manual of Determinative Bacteriology - Provides identification Schemes based on Cell wall composition, morphology, differential staining, oxygen requirements, biochemical testing, serology, phage typing, amino acid sequencing, nucleic acid based methods (base composition, rRNA sequencing, DNA fingerprinting, PCR, nucleic acid hybridization). Spirochetes - Locomotion by means of two or more axial filaments. Treponema pallidum - Cause of syphilis. Borrelia - Members of this genus cause relapsing fever; also Lyme disease; diseases are transmitted by ticks. Leptospira - Leptospirosis - spread to humans from contaminated water; from urine of dogs, cats, rats, swine.
Aerobic/microaerophilic, motile, helical vibrioid, gram negative bacteria - Use flagella for locomotion rather than axial filaments; unlike spirochetes, these are rigid helices or curved rods; frequently microaerophilic. Campylobacter fetus - Cause spontaneous abortion in domestic animals. C. jejuni - Outbreaks of foodborne intestinal disease. Helicobacter pylori - Causes ulcers in humans. See Helicobacter
Gram negative aerobic rods and cocci - Pseudomonads - Many species; some excrete extracellular, water- soluble pigments into media. Pseudomonas aeruginosa - Produces a soluble, blue-green pigmentation; opportunistic- can cause infection of urinary tract, burns, wounds. Can cause septicemia, abscesses, meningitis. Trouble in hospitals - can grow on minute traces of unusual carbon source such as soap residues, cap-liner adhesives, in some antiseptics. Some are resistant to antibiotics; resistant genes are carried on plasmids.
Other gram negative rods Legionella - Causes legionellosis; colonize warm-water supply lines in hospitals and water in cooling towers of air conditioning systems. Neisseria - Frequently found on human mucous membranes. Neisseria gonorrhoeae - Causative agent of gonorrhea. Neisseria meningitidis - Causes meningococcal meningitidis. Moraxella - Aerobic coccobacilli. Moraxella lacunata - Causes conjunctivitis (pink eye). Brucella - Small non-motile coccobacillus; all are obligate parasites of mammals; causes brucellosis. Bordetella - Non-motile rod; virulent forms have capsules. Bordetella pertussis - Causes whooping cough. Francisella - Small pleomorphic bacteria. Francisella tularensis - Causes tularemia.
Facultative anaerobic gram negative rods - Very important medically; many cause diseases of the gastrointestinal tract; three important families: Enterobacteriaceae (enterics) - Inhabit the intestinal tracts of humans and other animals; some found as permanent agents; others present only in certain segments of the population; others present only as agents of disease. Distinguished from each other by biochemical tests; also serology; some are motile; others are non-motile; many have fimbriae to help attach to cells of mucous membranes; sex pili is used for exchange of genetic information; produce bacteriocins (proteins that interfere with the growth of other bacteria; maintains ecology). Escherichia coli - Facultative anaerobe; generally not considered pathogenic; can cause urinary tract infections; some strains produce enterotoxins, i.e. traveler's diarrhea; occasionally can cause very serious foodborne disease.
See E.coli (Go to "Microbes and Disease" at the middle of the site and click on E. coli
Salmonella - Almost all members of this genus are potential pathogens. Members of this genus are common inhabitants of intestinal tract of many animals, esp., poultry and cattle. With unsanitary conditions - can contaminate food. Need to identify for specific treatment. Numerous biochemical and serological tests for identification. There are over 2000 serovars (serotypes). Classification may be somewhat difficult. Salmonella typhi - Causes typhoid fever. This is the most severe of the infections by Salmonella spp. Infections by other Salmonella are referred to as salmonellosis. S. cholerasuis and S. enteritidis - These two species are the most common cause of salmonellosis. Serovar (serotypes) - Injection of flagella, or capsule or cell wall component into an animal like a rabbit will result in production of specific antibodies. Because of their specificity, these antibodies can be to help identify the different types of Salmonella. This method is referred to as the Kauffmann - White scheme. Biovar (biotype) - Biochemical tests can be used to identify the Salmonella. Shigella -Causes bacillary dysentry or shigellosis; travelar's disease. Some strains can cause a life threatening dysentry. Unlike Salmonella, Shigella can be found naturally in humans. See Food Borne Disease
Klebsiella - Can cause a pneumonia; a hospital acquired infection. Serratia marcescens - Red pigment; a hospital acquired infection; can cause urinary and respiratory tract infections. Proteus - Very active motile bacteria. Can cause urinary tract infections; also infect wounds and can a cause of infant diarrhea. Yersinia pestis - Causes plague (Black death of middle ages). Rats and squirrels can carry the bacteria. Transmitted by fleas. Enterobacter E. cloacae and E. arogenes - Hospital acquired infections; urinary tract infections.
Vibrionaceae, Gram Negative, Facultative Anaerobic Rods; Many slightly curved Vibrio cholerae -Causes cholera; watery diarrhea. Vibrio parahemolyticus - Causes a gastroenteritis; from raw or under cooked fish.
See Symptoms
Pasteurellaceae, Gram Negative, Facultative Anaerobic Rods Pasteurella multocida - Causes septicemia in cattle; fowl cholera in chickens and other fowl; pneumonia in some. May be transmitted to humans. Hemophilus - Group commonly inhabit mucous membranes of humans. Hemophilus influenzae - Common cause of meningitis; also common cause of ear aches. Hemophilus ducreyi - Cause of a sexually transmitted disease chancroid.
Gardnerella Gardnerella vaginalis - Most common cause of vaginitis.
Anaerobic, Gram Negative, Straight, Curved, and Helical Rods Bacteroides - Group of microbes that live in the human intestinal tract (1 billion/g of feces. Some live in the gingival crevice. Infection of deep wounds. Fusobacterium - Slender bacteria with pointed ends. Cause dental abscesses.
Rickettsias and Chlamydias - Obligate intracellular parasites. Can reproduce only within a host cell. Rickettsias - Transmitted to humans by insects and ticks. R. prowazeki - Transmitted by lice; causes epidemic typhus. R. typhi - Endemic murine typhus; transmitted by a rat flea. R. rickettsiae - Rocky Mountain spotted fever - Transmitted by ticks. Coxiella burnetii - Q fever. Chlamydias - Do not require insects or ticks for transmission. Chlamydia trachomatis - Causes trachoma, common cause of blindness in humans. Also causes a nongonococcal urthritis; sexually transmitted. Also a cause of lymphogranuloma venerum. C. psittaci - Causes psittacosis. C. pneumoniae - Causes a mild form of pneumonia in young adults.
Mycoplasmas - Small pleomorphic bacteria. M. pneumoniae - Walking pneumonia
Gram Positive Cocci Staphylococcus aureus - Grow well in nasal secretions and on skin (high salt concentration). Can grow in ham and other cured meats - high osmotic pressure, or low moisture. Common pathogen in hospitals. Develops resistance to antibiotics. Produces many toxins, like the toxin responsible for toxic shock syndrome. Also can produce an enterotoxin and is therefore a common cause of food poisoning.
See S. aureus infected intestine (Go to "Microbes and Disease" at the middle of the site and click on S.aureus)
Streptococcus pneumoniae - Produces extracellular substances; enzymes that help spread the infection; can dissolve fibrin.
Endospore Forming, Gram Negative Rods and Cocci - Endospore are resistant to heat and to many chemicals; most endospore-forming rods and cocci are gram positive. Bacillus anthracis - Causes anthrax in cows, sheep and horses; can be transmitted to humans. Gram positive rod with a centrally ocated endospore. It is a non-motile facultative rod. Clostridium - Obligate anaerobic bacteria. C. tetani - Causes tetanus. C. botulinum - The cause of botulism. C. perfringens - The cause of gas gangrene; also a food borne diarrhea.
Regular Non-spore forming gram positive rods Lactobacillus - Produce lactic acid as an end product of glycolysis; Considered normal flora in the vagina, intestinal tract, and oral cavity; Acidity inhibits competing potential pathogens. Listeria monocytogenes - Can contaminate food, esp. dairy products. Survives within phagocytes; can cause stillbirths or do serious damage to fetus.
Irregular Non-spore forming gram positive rods Corynebacterium - Pleomorphic bacteria Corynebacterium diphtheriae - Causes diphtheria Propionibacterium acnes - Commonly found on skin; one of the causes of acne.
Mycobacterium - Acid-fast, drug-resistant, pathogenic characteristics are related to the cell wall. The cell wall is like gram negative bacteria except that LPS is replaced by mycolic acid. Mycolic acid forms a waxy, water-resistant layer. M. tuberculosis - Causes tuberculosis M. laprae - Causes leprosy
Nocardioforms Nocardia asteroides - Difficult to treat pulmonary nocardiosis.
Chapter 12
Fungi - More than 100,000 species; about 100 are pathogenic to humans and animals. Most are aerobic or facultative anaerobic; few are anaerobic. Mycology - Study of fungi Mycosis - Fungal infection Mycoses (plural) - Are generally chronic, because fungi grow slowly. Five groups according to degree of tissue involvement and mode of entry into the host. Systemic mycoses - Infection is not restricted to any one part of the body. May affect a number of tissues and organs. Infections are generally acquired from inhalation of spores from the soil. Generally not contagious from animal to human or human to human. Two important systemic mycoses: Histoplasmosis and Coccidiomycosis. Subcutaneous mycoses - Fungal infections beneath the skin; Infection by direct implantation of spores or mycelial fragments into a puncture wound in the skin. Cutaneous mycoses - Fungi infect only the epidermis, hair and nails. Fungi called dermatophytes. Infection is transmitted from human to human by direct contact or by contact with infected hairs or epidermal cells. Superficial mycoses - Fungi are localized along hair shafts and on surface of epidermal cells. Opportunistic pathogen - Normally harmless; can become pathogenic under following conditions: seriously debilitated or traumatized patient; following treatment with broad spectrum antibiotics; immune system is depressed by drugs or immune disorder. Candida albicans - Opportunistic causing yeast infections.
Protozoa - Kingdom Protista; unicellular, eucaryotic; 20,000 species; few cause disease. Amoeba - Use pseudopodia for movement and gathering food. Entamoeba histolytica - Causative agent of amoebic dysentery; is the only amoeba found in human intestines. Its primary food are red blood cells; transmitted between humans through ingestion of cysts that are excreted in the feces of an infected person. Naegleria - Crosses mucous membranes and may infect the human brain. Parasite in warm water and may be acquired from swimming. Found in the Rio Grande last year. Acanthamoeba - In water (sometimes in tap water); Can infect the cornea and may cause blindness.
Flagellates - Use flagella fro locomotion. Trichomonas vaginalis -Found in the vagina and in the male urinary tract. Transmission is by sexual intercourse; also by toilet facilities or towels. Giardia lamblia - Found in the small intestines of humans and other mammals; excreted in the feces; survives the environment, then ingested. Hemoflagellates - Blood parasites; found in the circulatory system of bitten hosts; transmitted by bites of blood-feeding insects. Trypanosoma T. brucei gambiense -Transmitted by the tsetse fly. T. cruzi - Causative agent of Chagas' disease; transmitted by the "kissing bug". Insect bites, then may defecate. The trypanosomes in the feces may enter the bite wound.
See Parasite
Ciliates - Use cilia for locomotion. Balentidium coli - Causes a severe, rare type of dysentery. Apicomplexans - Complex life cycle involving several hosts. Plasmodium vivax - Causes malaria; Anopheles mosquito with sporozoites in its salivary glands bites a human injecting sporozoites; the sporozoites travel through the blood stream to the liver where infection takes place and merozoites are produced. The merozoites enter the blood stream and infect red blood cells where male and female gametocytes are produced. The cells rupture releasing the gametocytes. Another mosquito becomes infected after feeding on the human. The gametocytes are ingested into the intestinal tract of the mosquito where sexual reproduction occurs with production of sporozoites. The sporozoites migrate to the salivary glands. Babesia microti - Parasite of red blood cells; transmitted by ticks. Toxoplasma gondii - Intracellular parasite of humans; Its life cycle involves cats. Cryptosporidium - Causes respiratory and gall bladder infections in immunocompromised patients, like those with AIDS.
Helminths - Multicellular, eucaryotic worms - Parasitic worms which lack a digestive tract. Absorb nutrients from the host's food, body fluids and tissues. Platyhelminths - Flatworms Trematodes - Flukes Clonorchis sinensis - Asian liver fluke; seen in immigrants to the U. S.; Cannot be transmitted to the humans in the U. S. because the intermediate host does not live in the U. S. Schistosoma - Blood fluke Cestodes - Tapeworms; intestinal parasites; lack a digestive tract; absorb food through their cuticle. Taenia saginata - Beef tapeworm; live in humans; may grow to 6 m in length. Proglottids with 100's of eggs are excreted in the feces. The eggs are ingested by grazing animals, the eggs hatch producing larvae that bore through the intestinal wall. Larvae migrate to muscles (meat) where they encyst as cysticerci. The meat is eaten by humans. The scolex (head of parasite) is not digested and it anchors to the wall of the small intestine producing proglottids. Taenia solium - Pork tapeworm.
See Parasitic Worm Eggs (Go to "Parasites" at the middle of the site and click on worm eggs)
Nematodes - Roundworms. Enterobius vermicularis - Pinworm; live in the human large intestine; the female migrates to the anus and deposits its eggs in the perianal skin. Ascaris lumbricoides - Small intestine of man. Necator americanus - Adult hookworm; small intestine of humans. Trichinella spiralis - Causes trichinosis; parasite in poorly cooked pork.
Chapter 13
Viruses - Contain a single type of nucleic acid, either DNA or RNA; contain a protein coat that surrounds the nucleic acid; some may contain an envelope of lipid, protein and carbohydrate; multiply inside living cells using the synthesizing machinery of the infected cell; cause the synthesis of specialized structures that can transfer the viral nucleic acid to other cells; viruses have no enzymes for protein synthesis and ATP generation; viruses must use the metabolic machinery of the host cell to multiply. Host range - The different host cells that a virus can infect; viruses multiply only in cells of particular species; host range depends on the ability of the virus to attach to a particular cell and on the availability of cellular factors required for viral multiplication. Virus size - Ranges from 20 to 300 nm in diameter. Viral structure - Helical, polyhedral, e.g. icosahedral, enveloped, or Bacteriophage replication - Attachment, penetration, biosynthesis of complex viral components, maturation, lysis.
See Bacteriophage
Enumeration of bacteriophages - Number of plaques equals number of viruses (may need to dilute virus stock to get readable plates). Growth of animal viruses - Use live animals, embryonated eggs, cell culture. Living Animals - Some viruses grow only in living animals; observe for signs of disease or examine tissues for signs of viral infection (can use electron microscope). Embryonated eggs - Inject embryonated eggs with virus; death of embryo means infection; may look for pocks or lesions on membranes (chorioallontoic membrane for e.g.). Cell culture - Infect a cell monolayer in culture; look for cytopathic effect (CPE). CPE - Cells round and may detach from glass or plastic surface; cells usually die. Primary cell line - From tissue for e.g.; die after a few generations; diploid cell lines live for several hundred generations and are widely used for diagnostic purposes. Continuous cell lines - Transformed cells; live as long as they are passaged using fresh medium; generally a cancer cell line; HeLa cell line from a cervical cancer from a woman who died in 1951; good for growing viruses. Animal virus replication (DNA virus) - Attachment, penetration, uncoating, early transcription, early translation and synthesis of enzymes, DNA replication, late transcription, late translation, synthesis of capsid proteins, maturation (assembly), release; Early genes --> mRNA--> enzymes needed for the multiplication of viral DNA; Late genes--> mRNA--> proteins needed for capsid
See Virus Structure
See Virus Structure 2
See Viruses Big Picture
Classification of viruses - Based on nucleic acid replication ssDNA viruses, nonenveloped - Parvovirus, coinfection with adenovirus; cause fetal death, gastroenteritis dsDNA viruses, nonenveloped - Adenovirus, cause respiratory infections; some cause tumors in animals. Papillomavirus and polyomavirus - small viruses that induce tumors; human warts, cancer in animals. dsDNA, enveloped Poxvirus - vaccinia; smallpox (variola); Molluscum contagiosum (wart-like lesion); cowpox Herpesvirus - Simplexvirus (fever blisters); Varicellavirus (varicella zoster: chickenpox; shingles); Cytomeglovirus (mononucleosis, venereal disease); Epstein Barr virus (infectious mononucleosis); Lymphocryptovirus (Burkitt's Lymphoma) Hepadnavirus (Hepatitis B virus; RT: RNA---> DNA) liver tumor. ssRNA, nonenveloped, + strand Picornavirus - Enterovirus, Rhinovirus; Hepatitis A virus. Poliovirus; Coxsackie (myocarditis, et al.) Echovirus (intestinal disease); Rhinovirus (colds). ssRNA, enveloped, + strand - Alphavirus (equine encephalitis); Rubivirus (rubella); Flavivirus (arthropod ---> humans); Pestivirus (yellow fever, dengue, encephalitis); Hepatitis virus C; Coronavirus (URT infections, common cold). ssRNA, - strand - Vesiculovirus (bullet-shaped with spiked emveloped) vesicular stomatitis virus; Lyssavirus (animal diseases including rabies); Filovirus (enveloped, helical virus such as Ebola virus and Marburg virus); Paramyxovirus (parainfluenza, mumps); Morbillivirus (measles virus; Newcastle disease virus in chickens). msRNA, - strand - Influenzavirus A and B (enveloped spikes that agglutinate RBC); Influenza C; Bunyavirus and Hantavirus (hemorrhagic fever; pulmonary syndrome associated with rodents); Arenavirus (lymphocytic choriomenigitis; hemorrhagic fever).
See Influenza Produce DNA - Retrovirus (all RNA tumor viruses; ds RNA virus) Oncoviruses; Lentivirus (leukemia; HIV)
See HIV
Chapter 14
Pathogen - Disease causing. Pathology - Scientific study of diseases. Etiology - The cause of disease. Pathogensis - Manner in which a disease develops. Infection - Invasion or colonization of the body by pathogenic microoganisms. Disease - Change in the state of health because of an infection - abnormal state - body cannot carry on its normal functions; an infection may occur in the absence of detectable disease; AIDS infection without detectable disease. Normal Flora - The microorganisms that establish a more or less permanent residence (colonize) but do not produce disease under normal conditions; Fetus in utero is germ-free. When it passes through the birth canal (passes through the vagina) the newborn comes in contact with microorganisms; also eats, breathes, and comes in contact with microorganism in the environment some of which colonize different parts of the body. These microbes are generally beneficial to the host because may produce vitamin K or may interfere with the growth of potential pathogens (microbial antagonism). Transient Flora - May be present for several days, weeks, months, then disappear Microbial antagonism - Microbes live in balance with each other and with the body; adult human vagina has a pH between 3.5 and 4.5 because of acid produced by normal flora. This pH keeps other microbes in check, e.g. Candida albicans. If normal flora are killed (antibiotics), then the vaginal pH may change to pH 7.0 and this pH will allow C. albicans to grow and cause an infection. Another example: E. coli interferes with the growth of other bacteria in the colon because E. coli produces colicins. Symbiosis - Living together; host and normal flora live together. Commensalism - Symbiotic relationship in which one organism benefits but not the other. No harm is done to the host; Many bacteria live on secretion produced by the host or on sloughed-off cells. Mutualism - A type of symbiosis that benefits both organisms; E. coli in the colon eats waste and produces vit. B. Parasitism - Another type of symbiosis; one organism benefits at the expense of the other. Many disease-producing bacteria are parasites. Opportunistic organisms - Potential pathogens that ordinarily do not cause disease unless they gain entry into "inner" parts of the body; E. coli lives in the colon, but may be pathogenic in the urinary tract, lungs or spinal cord; vagina example, i.e. at pH 7.0 will allow the opportunistic C. albicans to grow. If the immune response is depressed, then non-pathogens may become pathogenic such as with AIDS in which CD4+ T cells are attacked by the virus and destroyed. Pneumocystis carinii, a protozoan and an opportunistic organism, may cause pneumonia in AIDS patients. Etiology of Infectious Diseases - Cause of disease. Koch's Postulates - Dead animal--> isolate and identify microogranism--> animal--> disease (same as in the first animal)--> isolate and identify microorganism (same as that identified for the first animal); Exceptions: Some infectious agents cannot be cultured, e.g. Legionella pneumophila (Legionnaire's disease) The etiologic agent determined by taking pt.'s lung tissue---> guinea pig--> pneumonia-like symptoms--> lung tissue from guinea pig--> yolk sac--> microscopy--> rod-shaped bacteria. Second exception: some pathogens can cause several pathologies, e.g. Streptococcus pyogenes can cause sore throat, scarlet fever, skin infections, puerperal fever, osteomyelitis.
Classifying Infectious Diseases Communicable disease - Spread from one host to another, e.g. chicken pox, measles, tuberculosis. Noncommunicable diseases - Not spread from one host to another, e.g. deep wound with Clostridium tetani under anaerobic conditions will allow micoorganism to produce toxin which affects the CNS.
Occurance of Disease Incidence - The fraction of the population that contracts the disease during a period of time. Prevalence -The fraction of the population having the disease at a specific time. Sporadic disease - Particular diseases that occur only occasionally, e.g. typhoid fever. Endemic disease - A disease that is constantly present in a population, e.g. the common cold. Epidemic disease - Many people in a given area acquire a certain disease in a relatively short period of time, e.g. AIDS in San Francisco. Pandemic disease - An epidemic disease that occurs worldwide, e.g. Influenza. See Influenza Pandemic
Severity or Duration Acute disease - One that develops rapidly but lasts only a short time, e.g. Influenza. Chronic disease - Develops more slowly, body's reactions are less severe, continual or recurrent for long periods of time, e.g. tuberculosis, Infectious mononucleosis. Subacute disease - Intermediate between acute and chronic. Latent disease - The causative agent remains inactive for a period of time, then becomes active to produce symptoms of the disease.
Extent of Involvement Local infection - The invading microorganisms are limited to a relatively small area of the body, e.g. boils, abscesses. Systemic or generalized infection - Microorganisms or their products are spread throughout the body by the blood or lymphatic system, e.g. measeles Focal infection - Local infection (e.g. teeth, tonsils, or sinuses)--> blood stream or lymph vessel--> other parts of the body. Bacteremia- Presence of bacteria in the blood. Septicemia - Bacteria actually multiply in the blood. Toxemia - Presence of toxins in the blood. Viremia - Presence of viruses in the blood. Primary infection - Acute infection that causes the initial illness. Secondary infection - One caused by an opportunistic microbe after primary infection has weakened the body's defenses. Subclinical infection - One that does not cause any noticeable illness.
Spread of infection Reservoirs - Continual source of a disease. Human reservoirs - Humans that carry or harbor pathogen (best reservoir); Some harbor and transmit to others without exhibiting any signs of illness; called carriers; AIDS, diphtheria, typhoid, gonorrhea. Animal reservoirs - Sylvatic (wild); domestic; zoonosis; disease from animal to human; rabies, bubonic plaque; over 150 zoonotics known. Nonliving reservoirs - Soil-->fungi-->mycosis; soil-->Clostridium; ater-->feces from humans and other animals (G.I. tract diseases).
Transmission of Disease Contact transmission - Spread of disease by direct contact or droplet; person to person, e.g. measeles, scarlet fever, smallpox, sexually transmitted disease (AIDS); animal to person, e.g. rabies, anthrax. Indirect contact transmission - Transmitted from a reservoir to a susceptible host by means of a non-living object; a non-living object is called a fomite (towels, bedding, diapers). Droplet infection - Droplets of saliva or mucus spread by coughing, sneezing, laughing, talking; usually travel less than one meter.
Common vehicles of transmission - Transmission of disease by a common, inanimate reservoir to an individual; the common inaimate reservoir may be food, water, drugs, blood, e.g. Shigellosis or Salmonellosis. Airborne transmission - Spread of agents of infection by droplet nuclei or dust; usually travel more than 1 m between host and reservoir; mouth or nose --> coughing, sneezing, laughing, talking--> droplet (microbe)--> measeales, TB, Q fever, common cold. Vectors - Animals that carry pathogens from one host to another; arthropods (ticks) are the most important. Mechanical transmission - Insect body parts. Biological transmission - Bites; animal (bite by insect)--> human (bite by insect). Portals of entry - Preferred entry of microbe into host; e.g. mucus embrane and skin.
Portals of exit - Route of exit of microbe out of host. Respiratory tract - Mouth, nose---> coughing, sneezing--> TB. Gastrointestinal tract - Feces--> Salmonella. Urogenital tract - Sexually transmitted diseases. Skin - Drain of wound. Blood - Infected with AIDS virus.
Nosocomial infections - Infections acquired as a result of a hospital stay; from 5% to 15% of all hospital pts acquire some type of nosocomial infection; 20,000 people die annually from nosocomial infections; result from (1) microorganism in the hospital that is infectious; (2) the host is compromised (lowered immune response because of drugs, or illness. Microorganisms in the hospital - Major reservoir for a variety of pathogens; Staphylococcus aureus was a major pathogen in the past; now E. coli, Pseudomonas aeruginosa (opportunists) esp in surgery and burn pts; Microorganisms have R-factors, sometimes multiple, therefore resistant to different drugs. Compromised host - Resistance to infection is impaired by disease, therapy, or burns; (1) broken skin or mucous membrane - break barrier; (2) a suppressed immune system, e.g with drugs, radiation, steroids, other (T cells down); (3) impaired cell activity, e.g. malnutrition, cirrhosis of liver (B cells down). Chain of transmission - Direct contact by hospital staff; patient to patient; fomite (urinary catheter, intraveneous cathater, needles); ventilation system; specilaized area for congregation of patients. Control of nosocomial infections - Reduce number of pathogens to which the patient is exposed; use aseptic technique; handle contaminated material carefully; hand washing; educating personnel; isolation rooms. Patterns of disease - Reservoir (source)-->Transmission (direct contact; indirect contact; vectors)--> susceptible host (invasion; mutiplication)--> Pathogenesis (extent varies, i.e. toxin, resistence).
Predisposing factors - Makes the body more susceptible to a disease; may change the course of the disease. Gender - Females have higher urinary tract infections than males; males have a higher incidence of pneumonia and meningitis than females. Genetic background - Sickle-cell anemia in Blacks; Blacks are more resistent to malaria than whites. Climate - weather - Temperate regions there is a higher incidence of respiratory diseases during the winter becouse people are indoors more and there is more person to person contact. Other - Inadequate nutrition, fatique, age, environment, life-style, occupation, emotional disturbances.
Development of disease Period of incubation - Infection (time interval)--> appearance of disease. Some diseases the intercal is always the same; for others it is variable; depends on the specific microorganism involved (virulence, number of infecting microbes, resistence of the host). Prodromal period - Characterized by early, mild symptoms of the disease (general aches, malaise, or specific symptoms). Period of illness - Disease is most acute; overt signs and symptoms of the disease, fever, chills, muscle pain, sensitivity to light, sore throat,lymph node enlargement, gastrointestinal disturbance; WBC count is either up or down; immune response overcomes the disease and the pt gets well; if not the pt dies. Period of decline - Signs and symptoms subside; fever decreases, feeling of malaise diminishes; period is short (24 hrs) occurs by crisis; if several days, fever declines slowly, occurs by lysis; pt is vulnerable to secondary infections. Period of convalescence - Return to normal; person regains strength; body returns to predisease state.
Epidemiology - Important to identify causative agent, esp. infectious agent; need to understand the mode of transmission and geographical distribution of the disease. Descriptive epidemiology - Collect data. Analytical epidemiology - Analyze data. Case reporting - Establish the chain of transmission. Centers for Disease Control - CDC; U.S. public Health Service branch, Atlanta, Ga; Morbidity and Mortality Weekly Report.
See Epidemiology
Chapter 15
Pathogenecity - The ability to cause disease in a host. Virulence - The degree of pathogenecity. Entry of microorganisms into a host - Entry through portals of entry. Mucous membranes - Membranes that line the respiratory tract, gastrointestinal tract, genitourinary tract, conjuctiva; many bacteria enter the body by penetrating mucous membranes. Respiratory tract- Droplets of moisture or dust (containing microorganisms) enters the respiratory tract via the nose or mouth, then to the throat, bronchi and lungs; diseases include common cold, pneumonia, TB, flu (orthomyxovirus), measeales (paramyxovirus). Gastrointestinal tract - Food, water, dirty fingers placed in mouth, et al.; microbes enter the stomach (pH 1.0 because of Hcl), then may pass to duodenum (alkaline), intestinal tract (may encounter destructive enzymes), then excreted as feces. Diseases include mumps (paramyxovirus), polio (picornavirus), Hepatitis A (picornavirus), typhoid fever (Salmonella typhi), Amaebic dysentery (Entamoeba histolytic), bacillary dysentry (Shigella spp.), cholera (Vibrio cholerae). Genitourinary tract - Sexually transmitted: syphilis (Treponema pallidum), gonorrhea (Neisseria gonorrheae), herpes (herpes virus), AIDS (human immunodeficiency virus; HIV), Chlamydia, Trichomonas vaginalis. Skin - Important barrier; microbes might enter through openings in the skin, such as hair follicles, or sweat glands; Staphylococcus aureus or Propionibacterium acnes. Parental Route - Directly into the tissues beneath the skin or mucous membrane; from punctures, injections, bites, wounds, surgery (Not by mouth). Preferred portal of entry - Cause disease when introduced into the host through a preferred portal of entry, e.g. Salmonella typhi will show all signs and symptoms when swollowed (preferred route, but will show no reaction or a mild reaction when introduced under the skin. Streptococci if inhaled may cause pneumonia, but if swolled may show no signs or symptoms of disease. Some pathogens have more than one portal of entry. Number of invading microbes - If a small number enter there may be no disease because the immune system removes the invader; high numbers may cause disease; LD50 is the lethal dose 50 or the number of bacteria required to kill 50% of injected test animal. Adherence - Attachment of microbes to cells of the host. This is necessary for pathogenesis; attachment is through surface molecules called adhesins; the host molecules and the bacterial molecules have complementary conformations which detemines which tissues will be infected, e.g., Streptococcus mutans causes tooth decay because the glycocalyx is able to attach to the surface of teeth; E. coli (pathogenic) can attach to cells of the small intestines if certain pili are present on the bacterium; Neisseria gonorrhaea attach to cells in the genitourinary tract, eye, and pharynx if the bacterial cells have pili. Pathogens penetrate host defenses - Most must penetrate tissues to cause disease. Capsules - The presence of capsules (glycocalyx) increases the virulence of pathogens because of resistence to phagocytosis; examples of microbes having capsules are Streptococcus pneumonia (lobar pneumonia), Klebsiella pneumonia (bacterial pneumonia), Hemophilus influenzae (pneumonia and menigitis in children), Bacillus anthracis (anthrax). Cell wall components - M protein in Streptococcus pyogenes; this microbe uses M protein to attach to epithelial cells; it also resists phagocytosis. Enzymes - Produced by some bacteria as exoenzymes; enzymes are secreted from bacteria. Leukocidins - Destroy neutrophils and macrophages. Hemolysins - Lyse red blood cells. Coagulases - Clot fibrinogen in blood. Kinases - Break down fibrin, i.e. dissolve blood clots, e.g. streptokinase Hyaluronidase - Dissolves hyaluronic acid, the polysaccharide that holds certain cells of the body together. Collagenase - Breaks down collagen (protein that forms connective tissue).
Damage to host cells Direct damage - Break down cells, then can attack other cells. Toxins - Poisonous substances. Toxigenicity - The capacity to produce toxins. Toxemia - Symptoms caused by toxins in the blood. Exotoxins - Proteins (many are enzymes) produced inside bacterium and released to the surrounding medium, e.g. diphtheria toxin produced by Corynebacterium diphtheriae; botulinum toxin (neurotoxin) by Clostridium botulinum; tetanus toxin by Clostridium tetani (neurotoxin causing uncontroable muscle contraction, i.g. lockjaw); Staphylococcus enterotoxin by Staphlococcus aureus (affects the intestines, i.e. food poisoning), toxic shock syndrome is another example of a disease caused by an exotoxin. Endotoxin - LPS from gram negative bacterial cell walls; causes fever (pyrogenic).
Chapter 16 Resistance - The ability to ward off disease through our defences. Susceptibility - Vulnerability or lack of resistence.
Resistance Nonspecific - Defenses that protect us from pathogens in a non-specific manner Specific - Defense against a particular microorganism or its toxins; includes antibodies and special cells of the immune system. Non-specific defense - First line of defense; skin, mucous membranes; may be mechanical or chemical.
Mechanical factors Skin - Barrier; it is composed of keratin, a layer of tightly packed cells called the epidermis, and the dermis. Mucous membrane - Barrier; composed of epithelial layer that secretes mucus that prevents it from drying and a connective layer; the mucus is viscous and traps microorganisms; lines the GI tract, respiratory tract, urinary tract, and reproductive tract. Eye - Washing action of tears. Bronchi - Cells possess cilia which have a whip-like action; these mechanically move mucus (with trapped bacteria and dust particles, et al.) up the throat; coughing and sneezing sppeed up upward movement. Urinary tract - Urination has a clensing action of the uretha. Vagina - Secretion move organisms out of the female body.
Chemical factors Skin - Sebum, the oily substance that prevents hair from drying, contains unsaturated fatty acids that inhibit pathogenic bacteria and fungi; skin has a pH of between 3 and 5 because of fatty acids and lactic acid; perspiration conatins lysozyme. Intestinal tract - Gastric juices provide an adverse environment because of pH (1 to 3) HCl, enzymes, mucus. Other - Many other examples.
Phagocytosis - In Greek eat, cell; Injestion of microbes or particulate matter by cells Phagocytes - Cells in the body the phagocytose. Blood - Composed of fluid and formed elements and flows through the blood stream. Anticoagulants - Prevent blood from clotting; e.g. EDTA, heparin, citrate, other; Withdraw blood from an animal with a syringe containing anticoagulant will allow separation of blood into fluid called plasma and the formed elements. Plasma - Fluid of blood collected with an anticoagulant; contains proteins including albumin, antibodies, complement, the blood clotting proteins, such as prothrombin and fibrinogen; plasma also contains water and dissolved salts and buffers and other materials.
Formed elements - Red blood cells, white blood cells, and thrombocytes (platelets); can be differentiated using Wright's stain. Red blood cells - 4.8 to 5.4 X 106/mm3 ; transport of O2 and CO2. Thrombocytes (platelets) - 250,000 to 400,000/mm3. White blood cells - 5000 to 9000/mm3; phagocytosis, production of antibodies, other; includes granulocytes and agranulocytes. Granulocytes - White blood cells containing granules in their cytoplasm; includes neutophils, basophils and eosinophils. Neutrophiles - Make up 60 to 70% of the blood WBC; phagocytosis is their principle function; lobulated nucleus. Basophils - Make up 0.5 to 1% of the blood WBC; poorly phagocytic; contain dark purple staining granules when stained with Wright's; cells containing pharmocological agents such as histamine, which are important in inflammation and hypersensitivity reactions. Eosinophils - Make up 2 to 4% of the blood WBC; poorly phagocytic; important in inflammation esp., control; important in parasitic infections with worms. Agranulocytes - White blood cells lacking granules in their cytoplasm; include the lymphocytes and the monocytes. Lymphocytes - Make up 20 to 25% of the blood WBC; includes B cells and Tcells; important in the acquired or specific immune response. Monocytes - Make up 3 to 8% of the blood WBC; differentiate into tissue macrophages; important phagocytic cells; derived from the bone marrow from a stem cell; the stem cell differentiates into a monoblast which becomes a promonocyte; then enters the blood stream as a monocyte; the monocyte circulates in the blood stream for 12 hrs, then leaves the blood stream taking up residence in a tissue as a macrophage. Phagocytic activity - Neutrophils are much, much better than eosinophils which are better than basophils at phagocytosis. Macrophages - Tissue phagocytes that are extremely efficient phagocytic cells; derived from monocytes; their morphology and function changes significantly after leaving the blood stream as monocytes; macrophages are named according to the tissue in which they take up residence. Histiocyte - A fixed macrophage in the tissues. Kupffer's cells - Macrophages that line the sinusoids of the liver. Alveolar macrophages - Macrophages that line the alveoli of the lungs. Microglial cells - Macrophages that line the nervous system. Splenic macrophages - Macrophages in the spleen. Peritoneal macrophages - Macrophages present in the peritoneal membrane surrounding the peritoneal cavity. Phagocytosis or phagocytic process - Chemotaxis--> adherence----> injestion--> killing and digestion. Chemotaxis - Chemical attraction to site of infection; chemtaxins (chemoattractants) include such substances as bacterial breakdown products and complement component C5a. Adherence - Particles (bacteria, viruses, et al.) must adhere to the phagocyte if phagocytosis is to take place. The zeta potential (bacterial cells have an overall negative charge as do the phagocytes) must be neutralized; Opsonins are important in neutralizing the zeta potential. Opsonins - Molecules that neutralize the zeta potential between bacterial and phagocyte; opsonins enhance phagocytosis; opsonins include fibronectin (the universal opsonin), antibodies, C3b of complement. Injestion - The plasma membrane surrounds the opsonized particle and fuses around it; the particle is now within a vacoule called a phagosome; the phagosome makes contact with a lysosome (granules containing enzymes in the cytoplasma of phagocytes) and fuse forming a phagolysosome; the enzymes in the lysosome are released into the vacuole containing the particle. Digestion and Killing - Lysosomal enzymes include proteases, DNases, lipases, glycosidases which are digestive; the phagocyte undergoes anaerobic glycolysis producing lactic acid and a pH of about 4.0 (kills); myeloperoxidase, singlet oxygen, H2O2, and other factors are produced which are toxic to bacteria.
Inflammation - A physiological response by the body to injury, i.e. microbial infection, physical agents, chemical agents). Signs of inflammation - Redness (capillary dilation); pain (pressure on nerve endings); heat (increased blood flow); swelling (edema due to vascular permeability and cellular and fluid infiltration; loss of function. Benefit of inflammation - Destroy the injurous agent and remove; limit the effects by confining or walling off the agent; repairs or replaces damaged tissues.
Complement - Defense proteins in the blood stream that work in concert; two pathways, the classical and the alternative (alternate). Classical complement pathway - AgAbC1C4C2C3C5C6C7C8C9----> lysis; An antigen-antibody complex forms which activates C1; two IgG molecules or one IgM are required for activation; AgAb complex formation causes a conformational change on the Fc portion of the antibodies allowing interaction with C1q of the C1 complex (composed of C1q, C1r, and C1s; held together by Ca2+ ); conformational change on C1q causes a conformational change on C1r which then becomes an enzyme that attacks C1s; C1s cleavage make it an enzyme and it attacks first C4 and then C2; C4 is split into C4a and C4b and C2 is split into C2a and C2b; C4b and C2b attach to the membrane (bacterial cell wall, etc) and the C4bC2b complex becomes an enzyme that attacks C3; many C3's are attacked by each C4bC2b complex making this an amplification step; C3b attaches to the membrane at different sites becoming an opsonin, or interacts with C4bC2b to form C4bC2bC3b an enzyme that cleaves C5; C5 is split into C5a and C5b; C5b attaches to the membrane and interacts with C6, C7, C8, C9 forming the MAC (membrane attack complex); the MAC make holes (lesions) on the cell membrane allowing water and ions to flow into the cell causing an osmotic imbalance resulting in lysis.
Anaphylotoxins - C3a and C5a; degranulate mast cells and basophils allowing pharmocological agents such as histamine to leave the cell. Alternate Complement Pathway - Activation does not require antibodies; can be activated by LPS (gram neagtive bacteria) and petidoglycan (gram positive bacteria); uses C3b complexed to Factor B (C3bBb) to cleave C5 followed by the MAC to lyse cells.
Chapter 17 Antibodies - Glycoproteins in the blood stream that specifically interact with the foreign agents that induced them; can be separated into four classes in man called IgG, IgM, IgA, IgD, and IgE. Serum - Blood obtained without an anticoagulant will clot; if rimmed with a wood applicator stick, the clot will retract; the fluid is called serum; serum contains antibodies, complement, albumin and other proteins except the proteins that went into forming the clot (prothrombin, fibrinogen etc.). Electrophoresis - Movement of molecules when exposed to an electric field in an electrolyte buffer; the proteins will migrate in four or more groups; from + to - poles, albumin, a, b, and g globulins in that order; the g globulin fraction contains the antibodies. IgG - Composed of two light chains and two heavy chains connected by interchain disulfide bonds; has two reactive sites for antigen; cross the placents; seen in highest concentration in the 2o response; it takes two to activate complement. IgM - Composed of ten light chains and ten heavy chains in which five basic antibody structures are bonded to each other by disulfide bonds; has ten antigen reactive sites, but behaves as if it only had five; it takes one IgM to activate complement; seen as the primary antibody in the primary response. IgA- Composed of two antibody basic units (4 light chains and 4 heavy chains); possess a peptide called secretory piece; seen in secretions such as in mucus and in colostrum. IgD - Composed of two light chains and two heavy chains; present on B cells membranes. IgE - Composed of two light chains and two heavy chains; attached to basophils and mast cells by the Fc portion of the antbody allowing the antigen reactive sites to protrude from the cell and interact with allergen; important in the generation of inflammation and allergic responses.
Valence - The number of reactive sites on antigens and antibodies; IgG has a valence of two; bovine serum albumin has a valence of six. Antigens - Molecules that are foreign to an animal and react specifically with antibodies that they induce. Properties of antigens - Foreign to the host (BSA is foreign to goat but not to cow), complex (proteins are complex, but not sugars, nucleic acids, lipids, synthetic polymers such as nylon); high molecular weight (must be 5000 or greater to be effective generally); soluble in tissues (gold , coal are not soluble in tissues); stable (add tyrosin to geletin and antibodies can be produced). Epitope - Antigenic determinants; the number of epitopes = the valence of an antigen.
Antibody - antigen reactions - Antibodies and soluble antigens precipitate in solution forming a lattice; particulate antigens agglutinate when reacted with specific antibodies e.g. blood typing. Naturally acquired active immunity - Immunity acquired by virtue of exposure to a microbe, foreign cell or toxin; the host produces the antibodies. Naturally acquired passive immunity - Immunity passed from mother to fetus across the placenta (IgG) or with the colostrum (IgA); the host gets preformed antibodies. Artificially acquired active immunity - Immunity acquired after a deliberate injection of a foreign antigen (vaccine); the host produces the antibodies. Artificially acquired passive immunity - Immunity after receiving antibodies that are preformed in another animal (antibodies from a horse immunized with tetanus toxoid). Immune response - First exposure to a specific antigen will result in a response called the 1o immune response; IgM is the priciple antibody; it is of short duration; Second and future exposures will result in a secondary response which is long lasting; IgG is produced primarily. Lymphocytes - B cells have Ig (immunoglobulin, i.e. antibodies) on their surface; B cells produce antibodies; T cells (in general) may be either CD4+ or CD8+; CD4+ cells (in general) are the helper cells; CD8+ (in general) are the killer cells. The HIV infects CD4+ cells because its attachment is via the CD4+ molecule. Antibody production (humoral immunity) - Antigen is processed by the macrophages and the epitope transported to the surface where it is presented to specific B cells (these cells have antibodies on their membranes that interact with the presented epitope) and specific CD4+ (helper) T cells (these cells have the T cells receptor (TcR) on their membranes that interact with the epitope); the macrophages secrete IL-1 which activates the T helper cells inducing them to produce IL-2; IL-2 activates the B cells causing them to proliferate (undergo mitosis) and differentiate (change into plasma cells and memory cells); the plasma cells produce specific antibodies; the memory cells circulate until, at a later date, they are stimulated to become plasma cells and produce more antibodies. Cell-mediated immunity - Antigen is presented by the infected or foreign cell to CD4+ (T helper cells) and to CD8+; the CD4+ T cells secrete IL-2 which activates the CD8+ T cells into becoming cytotoxic T cells (Tc) and now kill the target cell (virus-infected, cancer cell, transplanted cell). Vaccines - Immunogenic molecules that confer immunity without causing the full-fledged disease; molecules or microbes must be made impotent; inactivated or attenuated (lessening of virulence; vaccinia virus is attenuated form of smallpox virus; tetanus toxoid is tetanus toxin that has been treated with formaldehyde. DPT - Vaccine for diphtheria-pertussis-tetanus. Type IV Hypersensitivity - PPD is injected into the dermis (intradermis injection); if the subject has had a previous experience with M. tuburculosis he will experience a slowly evolving erythema (redness) and induration (hardened) reaction at the site of injection. This is a cell-mediated immune reaction in which T cells (and macrophages) infiltrate the injected site. The peak of reaction is in about 48 hrs and then gradually subsides.
Chapter 19 Type I Hypersensitivity - Anaphylactic reaction; mast cells and basophils absorb IgE antibodies because these cells have an Fc receptor for IgE; therefore the antigen reactive site (Fab) projects away from the cell leaving it free to react with antigen. When the person comes in contact with antigen, interaction takes place with antibodies at the cell surface, causing the cell to degranulate; degranulation results in release of histamine and other pharmacological agents; histamine causes contraction of smooth muscles (bronchi, intestines); may result in death. Desensitization - A allergen sensitive person is given increasing doses of allergen in hopes that the person will produce IgG (blocking) antibodies. These newly produced blocking antibodies will compete with IgE for the antigen (allergen). In this way the allergen is neutralized before it interacts with IgE on the mast cell surface. Type II Hypersensitivity - Cytotoxic reactions, such as in destruction of red blood cells by antibodies in mismatched blood transfusions; destruction of Rh+ red blood cells by the mother; destruction of antibody coated cells by a process known as ADCC. Complement may be involved in the cytolytic reaction, or may me effected by ADCC. Erythroblastosis fetalis - An example of Type II hypersensitivity. In erythroblastosis fetalis, an Rh- mother produces immunity in response to Rh+ red blood cells from an Rh+ fetus. Nothing happens to this first child, but because the mother has previously been stimulated by Rh+ cells, she has developed immunity to Rh+ red blood cells. The second child is at risk, because the mother's immune system destroys his Rh+ cells. Type III Hypersensitivity - Immune complex reactions. Antigen (serum for passive immunity) is introduced into a person who produces antibodies to this (these) antigen(s). The antigen and antibodies form large AbAg complexes which may be phagocytosed with release of enzymes that destroy host cells, or the complexes may clog blood vessels. Complement may be activated; mast may be degranulated with release of histamine.
Chapter 20 Chemotherapy - Drugs used for treatment of disease. Selective toxicity - Drug must act on the microbe and leave the cells of the host intact. Synthetic drugs - Drugs synthesized by chemical means in the laboratory. Antibiotics - Agents produced by bacteria or fungi that inhibit growth of microbes. Antibiosis - Inhibition of growth of microbes. Paul Ehrlich - Coined the term chemotherapy. Produced the drug Salvarson, an arsenic derivative, active against syphilis. Searched for the "magic bullet". Quinine - First chemotherapeutic drug; drug for treatment of malaria. Sulfa drugs - Synthetic drugs discovered in the 1930's. The first was Prontosil, an aniline dye metabolized in the animal with production of the active ingredient, a sulfanilamide. Related drugs are the sulfaniamides or sulfa drugs. Alexander Fleming - In 1928, discovered that the fungus, Penicillum notatum, inhibited the growth of Staphylococcus aureus, a gram + bacterium. Later the active antimicrobial agent produced by P. notatum was called penicillin. Antibiotics - Many different microorganism produce antibiotics. Not used because they are too toxic to humans or have no advantage over other drugs currently in use. Some of these antibiotics are used commercially, for example to treat feed for lifestock and preserving their shelf life. Selman Waksman - Discovered that Streptomyces, a soil, filamentous bacterium, produced an antibiotic, which he called steptomycin. Streptomycin is effective against M. tuberculosis. More than half of the antibiotics in use come from soil microorganisms.
See Streptomyces (Go to "Microbes and Disease" at the middle of the site and click on Streptomyces)
Source of antibiotics
Bacitracin - Bacillus subtilis, a gram positive rod. Polymyxin - Bacillus polymyxa, a gram positive rod. Amphotericin B - Streptomyces nodosus, an actinomycetes. Chloramphenicol - Streptomyces venezuelae, an actinomycetes. Tetracyclin - Streptomyces aureofaciens, an actinomycetes. Erythromycin - Streptomyces erythraeus, an actinomycetes. Neomycin - Streptomyces fradiae, an actinomycetes. Nystatin - Streptomyces noursei, an actinomycetes. Streptomycin - Streptomyces griseus, an actinomycetes. Gentamicin - Micromonospora purpurea, an actinomycetes. Cephalothin - Cephalosporium, a fungus. Griseofulvin - Penicillum griseofulvum, a fungus. Penicillin - Penicillum notatum, a fungus.
Development of chemotherapeutic agents - For bacteria, easy to develop because of their differences with eucaryotic cells, e.g. cell wall vs. plasma membrane, ribosome differences, metabolism differences. For eucaryotic pathogens, (fungi, protozoa, helminths (worms)), it is more difficult because resemble human cells more closely. For viruses, it is more difficult because viruses use host cell DNA for own structures. Attack virus may easily result in an attack of the host cells.
Spectrum of activity - Penicillin for e.g. will attack gram +, but only a few gram- bacteria. Therefore its range or spectrum of activity is somewhat narrow. Penicillin interferes with peptidoglycan synthesis. Broad spectrum antibiotics - affect a large number of gram+ and gram- bacteria. Chloramphenicol interferes with translation of mRNA, i.e. affects all cells producing protein. Broad spectrum drugs save time and is an advantage. Disadvantage is that they also attack normal flora and can allow opportunistic microbes to grow (superinfection). Superinfection - Infection, over and above the infection that is being , treated such as growth by opportunistic microorganisms. Growth of drug resistant microbes may also result in a superinfection.
Action of Antimicrobial drugs Cell wall - Penicillin prevents cell wall synthesis because it interferes with peptidoglycan (PG) synthesis. Affects gram+ bacteria. LPS and other material in the cell wall protect the little PG in gram- bacteria from penicillin. Bacitracin and vancomycin interfere with synthesis of linear strands of PG. Penicillin and Cephlosporin prevent cross-linking of PG. Inhibition of Protein Synthesis - All cells synthesize protein. DNA ---> mRNA ---> Ribosome --> Protein. Some antibiotics can attack selectively because of differences in ribosomes. Eucaryotic cells - 80s ribosomes Procaryotic cells - 70s ribosomes i.e. structural differences. Caution: mitochondria have 70s ribosomes similar to bacteria. Attack bacteria, attack mitochondria. Chloramphenicol inhibits formation of peptide bonds. Erytromycin reacts with 50s portion of ribosome. Tetracyclines interfer with attachment of tRNA carrying amino acids to the ribosomes. These drugs are selective because they do not penetrate mammalian cells very well. Streptomycin changes the shape of the 30s portion of the ribosome. mRNA misreads. Gentamicin same as Streptomycin.
Plasma Membrane Injury - Polypeptide antibiotics change the permeability of the plasma membrane. Results in loss of metabolites from the microbial cell. Polymyxin B attacks phospholipids of the membrane. Nystatin and Amphotericin B combine with sterols in fungal plasm a membrane. Disrupts the membrane. Bacteria - no sterols, no effect. Animal cells - sterols, can have an effect. Sterol is cholesterol. Fungal cells - sterols, can have an effect. Sterol is ergosterol. Nystatin and Amphotericin B have a greater effect on ergosterol than on cholesterol and with balance can attack fungus better than animal cells.
Inhibition of Nucleic Acid Replication - Drugs that inhibit DNA or RNA replication have a high chance of attacking host cells also because host cells also have DNA and RNA that replicates. This is why making specific antiviral drugs is more difficult.