Fractastorius

1486-1553. Germ theory of disease; not accepted until years later. Experimental proof non-existant 'til 1800s

Anton van Leeuwenhoek

1685. Used microscopes to find “animalcules”

Redi & spallanzani

1668 (R), 1776 (S). Enclosed meat experiment. “Disproven” because of lack of air

Edward Jenner

Immunisation. Milk maids immune to small pox (they have cow pox)

Louis Pasteur

Swan-neck flask experiment. Substance + air, but no spontaneous generation. 1897: Cholera bacteria lost virulence e/ time (attenuated). Important for immunization. Theory (1857) microorganisms cause disease by producing specific molecues.

Holmes and Semmelweis

Mid 1800s. Handwashing prevents transmission of infectious disease Puerperal fever

Lister

Spray air w/ phenol to protect open wounds from being infected

Robert Koch

Relationship between micro-organisms and disease

Erlich

Certain chemicals selectively destroy bacteria and do not affect the body cells (chemotherapy)

Flemming

(1942) penicillin. Penicillium notatum

Domgak

Prontosil --> sulfanilamide

Robert Whittaker

5 kingdoms. Animal, plant, myceteae/fungu, protista, prokaryotes/monera

Carl Woese

3 kingdom system. Bacteria, archaeabacteria, eukaryotes

Carl von Linne

Formal system of organizing, classifying and naming

Hans Christian Gram

1886. gram stain. Differential stain

Griffith

Transformation experiments in 1920s

Spontaneous generation theory

Life only arises from dead or organic matter

Bacteriology

Simplest, smallest, single-celled

Virology

Non-cellular, parasitic, living organisms

Mycology

Microscopic (molds and yeasts), macroscopic (mushrooms and puff balls)

Germ theory of disease

Disease transmitted by “invisible animals” or in this case germs

Swan neck flask

Capable of keeping bacterial spores from colonizing the organic material, but still providing air for “spontaneous generation”

Koch's postulates

1. Same microbe always associated w/ a particular disease

2. the microbe can be recovered and grown in pure culture

3. the pure culture must cause disease in experimental animals

4. the original microbe must be recovered from the experimental animal

problems: mycobacterium leprae requires animal host, Neisseria gonorrhoeae only human hosts and opportunistic pathogens only in immunocompromised hosts

Chemotherapy

The use of chemical agents that can selectively destroy pathogenic agent while leaving body cells unaffected

Salvarsan

A chemotherapeutic agent used against syphilis

Taxonomy

Kingdom, phylum, class, order, family, genus, species

Eukaryote properties

5-10um, algae/fungi have cell walls, hav nuclear membranes, have nuceolus, > 1 chromosome, chromosome associated proteins, large 80S ribosome, mitochondria for respirations, sexual/asexual repro, almost exclusively aerobic

Prokaryote properties

1-3um; mycoplasma have no cell wall, all others do; no nucleus or nucleolus; no chromosome associated proteins; small 70S ribosome; respiration in cytoplasmic membrane; asexual repro; aerobic, facultative or anaerobic

Candida albicans

Part of normal human flora

Fungi properties

Eukaryotic. Aerobic or facultative. Will grow axenically. Can be easily isolated by their colony. Sacrophetic, heterotrophic, non-photosynthetic. Haplophase is dominant, transient diplophase. Have hyphae. True branching. ~10X the size of bacterium

Axenical growth

Growth w/o others (non-parasitic)

Fungi cell wall

Made of chitin (homo-poly N-acetylglucoseamine). Interlaced w/ glucans (glucosyl polymers). Peptidomannans

Peptidomannans

In fungi, serve in place of LPS (which is bacterial)

Saprophytic

Recylce decomposed matter

Hyphae

A row of fungal cells. Can be septate or non-septate

Septate hyphae

Cells are divided with membrane between them, although communications between the cells may exist

Non-septate hyphae

No cell membrane diving septa into seperate cells

Fungal branching

Fungi have true branching w/ Y-shaped cell at fork. Bacteria have false branching w/ bent and partial cells at fork.

Fungal dimorphism

Same organism can exhibit two different forms. Mycelial or hyphal form and yeast form

Mycelial/hyphal forms

Usually @ sub-physiologic temperatures, reproduction may be asexual or sexual, distinct sexual forms are displayed

Yeast formed

Due mainly to physiologic temperature. Strictly asexual reproduction (budding). Oval morphology. Nothing distinct

Aspergillus sp.

Non-dimorphic. Always found in mycelial phase, even when in deep tissue infections

Torula sp.

Exist only as yeast. Most will at low temperature form pseudo-hyphae

Pseudo-hyphae

Not permanent growing structures w/ regularly spaced nuclei. Can not differentiate furthar to form structures such as aerial hyphae/mycelia, fruiting bodies, and/or rhizoids. Branching does not occur and arthrospores and chlamydiospores are not found

Candida sp.

Thought to be monomorphic (only yeast), but will have mycelial stage at sub-physiologic temperatures. Grows in mycelial form in biofilms

Fungi staining

All fungi are strongly gram+, all fungi are non-acid fast

KOH preparation

Works because warm KOH hydrolyses proteins and fungi are protected by a carbohydrate cell wall. Background cells will lyse as integral membrane proteins. Procedure: take scraping from margins of lesion (not center), add 2-3 drops of 10% KOH, warm slide over flame, optionaly add 1 drop lactophenyl cotton blue stain, put cover slip over liquid and examine immediately under high dry microscope objective

Alkali stain

Alternative to KOH/lactophenyl cotton blue. Make stain w/ Use “Super Quink” permanent black-blue int for fountain pens. Add solid KOH, 10 grams/100ml of ink. Centrifuge to remove precipitates and store in plastic bottle. Use mixture as stain.

Fungus culture

Primary step: isolation of culture: sabouraud's agar.

Secondary step: culture and species identification: Corn meal agar incubated at 25 celcius.

Sabourand's agar

Made from simple peptone (protein hydrolysate) and agar. pH is adjusted to 5.6 to kill bacteria. Bacteria grow faster and would thus over take the fungi on the plate

Corn mean agar

When incubated at 25 degrees celsius, allows for the growth of characteristic sexual structures for the differentiation of fungi via visual techniques (morphology v. biochemical)

Polyenes

Antifungal drugs from streptomyces sp. Binds to sterols (ergosterol) in the fungal cell membrane. This will form channels through the membrane causing leakage and eventual cell death. Toxic because they can weakly bind cholesterol. Also nephrotoxic.

Nystatin

A topical insoluble polyene

Amphotercin B

Parenteral use only. Administered as a colloidal suspension

Griseofulvin

Antifungal drug from Penicillium griseus. Acts on microtubules and mechanism of the mitotic spindle. Poorly absorbed so can not reach therapeutic levels in blood, but is deposited in keratinous tissue and builds effective concentration there. Only effective against dermatophytes and superficial mycoses

Flucytosine

Synthetic analog of cytosine. Gets incorporated into RNA after conversion to 5-flucouracil. Interferes w/ RNA formation and inhibits thymidylate synthetase. Toxic to bone marrow. Effective against Candida sp. Or Cryptococcus sp. No effect against molds. Oral administration

Synthetic azoles

Inhibit cytochrome enzymes. Also inhibit formtation of ergosterol from lanosterol precursor. Results in defective cell membrane. Fungistatic, not fungicidal. Used orally and parenterally. Effective against most systemic fungal infections. Some toxicity. Examples: ketoconazole, fluconazole, miconazole, itraconazole

Patassium iodide

Oral. Effective against Sporothrix schenkii

Tolnaftate

A napthiomate derivative. Topical: used only for dermatphytes

Undecalinic acid

A long chain fatty acid. Topical: used only for dermatphytes. Desenex

Allyamines

Contain napthalene ring

Terbinafine

Oral: used only for dermatophytes

Naftiline

Topical: used only for dermatphytes

Penlac nail lacquer

Prescription nail polish. Active ingredient is ciclopirox. Used to treat onychomycosis and / or perinychia. Does not have side effects of terinafine or itraconazole. Limited effectiveness in clinical trials. Less effective than oral medication

Class Ascomycetes

Class Basidiomycetes

Class Deuteromycetes

(Fungi imperfecti)

Asexual spores

Exogenous at ends or side of hypha

Exogenous at ends or side of hypha

Exogenous at ends or side of hypha

Sexual spores

Ascospores within sacs or Asci

Basidiospores on surface of basidium

Not yet found

mycelia

septate

Septate

septate

examples

Neurospora sp

Penicillium sp

Aspergillus

Filobasidiella neoformans (Cryptococcus neoformans)

all mushrooms, Rusts, Smuts

Epidermophyton sp.

Microsporium sp.

Trichophyton sp.

Spherical shape

Coccoid (coccus, cocci)

Cylindrical shape

Rod (bacillus, bacilli)

Curved shape

Vibrio. vibrates

Square shape

Not infectious

Chain arrangement

Strepto. Does not occur w/ bacilli

Cluster arrangement

Staphylo. Does not occur w/ bacilli

Pair arrangement

Diplo. Occurs w/ streptococcus pneumoniae

Gram stain

Purple/blue for gram positive. Red/pink for gram negative.

Place cells on slide, add primary stain (crystal violet), and mordant (Gram's iodine), add decolourizer (alcohol or acetone), add counterstain (saffranin)

Acid fast stain

Differential stain similar to Gram's. Used to differentiate Gram(-) bacteria. Mycobacterium

Ziehl Neelson staining

Acid-fast staining technique. Hot basic carbolfuchsin; decolourize w/ acid-alkali solutions; counterstain: methylene blue or malachite green. Acid fast red/pink; non acid fast: blue/green

Kinyou stain

Same as ZN but w/o heating

Fluorochrome stain

(auramine-rhodamine). Primary stain fluorescent dyes. Counterstain potassium permanganate. Organisms will fluoresce yellow/green against black background

Flagellum

Outer appendage; Organ of motility; not essential for survival; flexible; never for cocci; possible role in colonization. Compozed of 3 parts. Helical filament, hook and basal body. CW rotation is tumbling, CCW is smooth swimming. Propel at 20-90 um/sec

Monotrichous

flagellum at one pole

Amphitrichous

Multiple Flagella at both poles

Lophotrichous

Multiple flagella at one pole

Peritrichous

Flagella distributed around cell.

Helical filament

Inserted into hook. Composed of proteins (flagellin) (hauch, H antigen) 20nm diameter, 1-7 mm length

Hook

Short curved structure anchors filament into basal body

Basal body

Contains rod and 1 or 2 sets of double plates (rings). Located in cytoplasmic membrane and cell wall. 2 rings in Gram(+) and 4 rings in Gram(-) bacteria

H antigen

Helical filament of flagella.

Taxis

Involuntary movement in response to stimulus. Chemotaxis, aerotaxis, phototaxis, magnetotaxis. + response is towards stimulus (up gradient), - response is away (down gradient). Non-response is random walk. Chemotaxic receptors in cell membrane

Pilin

Protein component of pili and fimbriae

F-pilus

Sex pilus found in gram(-) bacteria only. Allows for entry of genetic material during conjugation

Fimbriae

Attachment pili. Allows for adhesion to surfaces. Predominantly Gram(-) some Gram(+). Found in Corynebacterium renale, and Actinomyces maeslundii

Glycocalyx

AKA Capsule, slime layer or S-layer. External mucilaginous layer. EPS. Bacillus anthracis has a polypeptide instead of a polysaccharide. Surrounds cell and is non-vital. Shows degree of organisation. Has a capsule and slime layer. Functions in adherence to species members and to surfaces. Allows for antiphagocytosis. Neutrophil killing not possible because lysosome contents do not have access to cell interior. Protects anaerobes from oxygen.

Slime layer

Part of glycocalyx w/ poor organization, weak attachment to cell wall

Capsule

Organized w/ adherence to cell wall (K antigen)

K antigen

Capsule. Cell wall antigen.

Streptococcus mutans

Responsible for dental carries via adherence of glycocalyx

EPS

Antigenic (K antigen). Found in S. pneumoniae, Haemophilus influenzae.

Streptococcus pneumoniae

Resists phagocytosis because of glycocalyx. Antiphagocytosis

B. fragilis

Capsule induces abscess formation

Quellung reaction

Swelling reaction that determines capsule presence. Antiserum + bacteria --> swelling. Specific antisera: capsular (K) antigens for typing

Peptidoglycan

Backbone of eubacteria cell walls. Composed of NAM & NAG linked with beta 1-4 glycosidic bonds. Provides rigidity and strength prevents osmotic lysis in dilute environments

Gram- v. gram+ cell wall

L-lysine is replaced w/ D-aminopimelic acid in gram(-) bacteria. Gram(+) has no outer membrane and only in some instances a periplasmic space.

Staphylococcus aureus cell wall

L-alanine branches off of NAM followed by D-glutamate and L-lysine. Gram(+)

Teichoic acids

i.e. Lipoteichoic acid. Phosphate + alcohol (gycerol/ribitol). Binds proteins (maintain low pH), cations (Ca²⁺ and Mg²⁺). Act as adhesins, virus receptor sites.

Gram(+) bacteria

(50-60% of dry weight) Composed of thick peptioglycans. Teichoic acids and additional carbohydrates and proteins. M, T and R proteins of Group A streptococci; protein A of Staphylococcus aureus

Lipoteichoic acid role in disease

Dermal necrosis (Schwartzmann reaction); induction of cell mitosis at the site of infection; stimulation of specific immunity; stimulation of non-specific immunity; adhesion to the human cell; Complement activation; induction of hypersensitivity (anaphylaxis)

Gram(-) cell wall

Thin peptidoglycan (5-10% of dry weight). Outer membrane contians porins (protein channels) for nutrient transport. Contain lipopolysaccharide (LPS) and lipoproteins. Gaps in cell wall allow acetone to seap out. 2 major layers, 8-11nm thick, always have periplasmic space, and is less penetrable than gram(+)

Gram(-) outer membrane

Prominent outer layer peripheral to periplasmic & peptidoglycan sacculus. Similar to cytoplasmic membrane (bilayer). External layer (LPS), inner layer – phospholipids. Outer membrane proteins

LPS

Inner most lipid anchors LPS to outer membrane. Toxic. O-polysaccharide long repeating sequence of sugars (O-antigen). An endotoxin

O antigen

Surface antigen from outer membrane. Polysaccharide in LPS. endotoxins

Endotoxin effects

Fever, haemorrhagic necrosis (Schwartzman reaction), disseminated intravascular coagulation, production of TNF, activation of the alternate complement pathway, stimulation of bone marrow cell proliferation, and enhancement of the immune and limulus lysate reaction (clotting of horseshoe crab amoebocyte lysates)

Acid-fast bacteria

Genera Mycobacterium & Nocardia. Peptidoglycan + arabinose & galactose polymers. Arabinogalactan esterification --> mycolic acids (waxy)

Lysozyme

Breaks beta 1-4 bonds between NAM & NAG. Present in body secretions (tear & saliva). Destroys all or part of cell. Leaves cells vulnerable to being lysed by osomotic pressure. Cell wall protects cells from swelling

Spheroplast

Portion of cell wall remains after attack by lysozyme

Protoplast

Cell wall is completely removed. Gram(+) more sensitive

Penicillin

Penicillin prevents cell wall formation. Inhibits formation of normal cross-linkages in peptidoglycan (brick wall w/o cement). Binds irreversibly to penicilin binding proteins

Penicillin binding proteins

Enzymes of peptidoglycan synthesis

Periplasmic space

Found in gram(-) bacteria. Space between inner and outer membranes. Gel like area containing a loose network of peptidoglycan. Contains: nutrient transport proteins, nutrient acquisition enzymes (proteases), detoxifying enzymes (beta-lactamases), membrane derived oligosaccharides (MDO), osmoprotectants

Axial filaments

Found in mobile bacteria that lack flagella. e.g. Spirochetes – Leptospira. Flagella-like filaments (chemically and structurally). Long thin microfibril inserted into a hook. Entire structure enclosed in periplasmic space. Endoflagellum

Cytoplasmic membrane physical properties

Inner membrane. General structure: 2 densely stained layers seperated by non staining region. 4-5nm thick. Phospholipid 30-40% and protein 60-70%. semipermeable barrier

Plasma membrane function

Active transport of metabolites, oxidataive phosphorylation (ETC and ATP productions), biosynthesis and export cell wall components, phospholipid biosynthesis, secretion of extracellular enzymes and toxins, and anchoring DNA during cell division (mesosome), chemotactic receptors are also in membrane

Protoplasm appearance

Granular appearance due to ribosomes. Site of biochemical activity, 70-80% water acts as solvent (sugars, salts and aa's)

Ribosomes

RNA/protein bodies (60% RNA, 40% protein). Composed of a 50S and 30S subunit. 70S in size. Sites of protein synthesis

Mesosomes

Extensive invaginations of cytoplasmic membrane continuous w/ cytoplasmic membrane. Function is unknown. Mainly seen in Gram(+) bacteria. Corynebacterium parvum

Chromatin area

No distinct membrane enclosed nucleus and no mitotic apparatus.

Bacterial chromosome

Single circular DNA (chromatin body). Exception: Streptomyces & Borrelia sp. have linear DNA. Rhodobacter sphaeroides (2 seperate chromosomes). DNA aggregated in one area (nucleoid). All genes are linked

Plasmids

Extrachromosomal DNA. Circular DNA smaller than chromosome. Self-replicating. Antibiotic resistance, tolerance to toxic metals, production of toxins, mating capabilities.

Inclusion bodies

Storage granules. (seen under light microscope). Poly-beta-hydroxybutyrate (PHB) has role in carbon & energy store. Membrane bound. mw 1000-256000 and up to 50% cell dry wt Bacillus subtilis. Polymetaphosphate granules. Glycogen granules

Endospores

Specialized structures produced in environmental stress. Resistant to UV, irradiation, chemical disinfection, drying. Requires specialized stains to see in light microscopy. Found in Bacillus and Clostridium spp. Contains complete nucleus, protein synthesis apparatus, energy-generating system (glycolysis), Ca-dipicolinic acid (10% dry wt, characteristic). Spore wall consists of peptidoglycan layer and cell wall germinating vegetative cell. The cortex consists of peptidoglycan w/ fewer cross-links. Coat: keratin-like protein. Impermeable layer (resistance to antibacterials)

Sporulation

Vegetative cell -> DNA condenses -> Transverse wall begins to form -> spore material seperated; formation of forespore -> vegetative cell grows around spore -> spore forms multilayered coating -> cell lysis frees spore

Germination

Outgrowth from spore gives rise to vegetative cell

Growth

Continuous macromolecular synthesis

Lag phase

The part of the growth curve in which there is no actual population change. Cells are preparing to begin divisions.

Exponential phase

Period of exponential growth w/ geometric increase in population due to abundance of resources

Stationary phase

Population plateus with multiplication equalling cell deaths. Can induce formation of endospores

Death phase

Decline in population (reverse log phase). Death is in geometric fashion.

Temperature

Minimum, optimum and maximum. Refering to temperatures allowing growth.

Psychrophile

Optimimum growth at below 15 degrees celsius. Capable of growing at 0 degrees and no growth at 20

Faculatative psychrophile

Can grow at below 20, but that is not there optimal temperature. Contaminants of food/dairy products

Mesophile

Optimal temperature between 20 and 40. includes human pathogens.

Thermophile

Optimum temperature greater than 45. not involved in infection.

Catalase

Converts hydrogen peroxide to water and oxygen

Peroxidase

H₂O₂ + NADH + H⁺ --> 2H₂O + NAD⁺

Superoxide dismutase

2O₂^- + 2H⁺ --> H₂O₂ + O₂

Obligate aerobes

Totally dependant on O₂ for growth. Require 20% oxygen. Possess catalase and superoxide dismutase.

Microaerophiles

Tolerate only 4% O₂. Possess SOD, but enzyme system can be overloaded inhibiting growth

Obligate anaerobes

Grow in absence of oxygen only. O₂ is lethal. Found in lower GI tract

Facultative anaerobes

Aerobic in the presence of oxygen and anaerobic only when oxygen is not available

Water activity

Index of amount of water. Same as relative humidity (i.e. 50% r.h. = .5 Aw). Most bacteria require Aw > .9 and grow optimally at Aw = 1.0

Xerotolerant

Survive at lower Aw. Fungi able to grow at Aw 0.60. salt tolerant bacteria (high solute, low water)

Trace elements

Mn, Zn, Co, Ni, Cu, Mo

Minerals

K+, Ca2+, Mg2+, Fe2+, Fe3+

Macronutrients

C, H, N, O, P, S. components of carbohydrates, lipids, nucleic acids and proteins

Autotroph

CO2 and soil primary C source

Heterotroph

Reduced/pre-formed organic molecules or other organisms. pathogens

Phototrophs

Light is used as energy source

Chemotrophs

Oxidation provides energy

Lithotrophs

Reduces inorganic molecules for H/e^-.

Organotrophs

Orgranic molecules are reduced

Complex medium

AKA non-synthetic medium. Composition unknown

Defined medium

Aka Synthetic medium. Chemical contents are known

All purpose medium

Supports the growth of most microorganisms.

Enriched medium

Basal support growth media + nutritive supplements added

Reduced medium

Addition of a reducing agent

Transport medium

Preserve microorganisms in transit following isolation from patient until cultivated

Selective medium

Allows one species to grow and suppresses others

Differential medium

Causes changes in medium that allow one to distinguish between species

Bactericidal

Killing of bacteria

Bacteristatic

Inhibition of growth of bacteria

Sterilization

All living cells, viable spores, viruses are destroyed or removed from object of environment

Sterilant

Chemical agent causeing sterilization

Disinfectant

Killing, inhibition or removal of microbes that may cause disease

Disinfectant

Agent that disinfects. Inanimate objects only. Chlorine, hypochlorites, chlorine compounds, copper sulphate, quaternary ammonium compounds.

Sanitization

Reduction of microbial population to that deemed acceptable

Antisepsis

Prevention of infection or sepsis

Antiseptic

Chemical applied to prevent sepsis. Not toxic, applied to living organism. Mercurials, silver nitrate, iodine solution, alcohols, detergents

Germicide

Kills pathogens and non-pathogens, but not endospores

Bactericide

Disinfectant/antiseptic effective against specific species. Also fungicide, algicide, viricide

Incineration

Burns/physically destroys. Needles, inoculating wires, glassware, etc.Vaporizes organic material, but can destroy substances

Boiliing

100 degrees. Kills everthing but endospores

Autoclaving

Everything will die! Steam under pressure at 121 degrees for 15 mins. 15Lbs/in² but heat labile substances will be denatured or destroyed (plastics). Must do full time for sterilization

Dry heat

160 degrees for 2hrs. Used for glassware or metal. Usefull for materials that must remain dry

Intermittent boiling

3x30 min intervals will kill off endospores

Pasteurization

72 degrees/15 secs. Similar to batch method. For milk conductive to industry. Fewer undesirable effects on taste and quality

Irradiation

Destroyes/distorts nucleic acids. UV common object surfaces. X-rays and microwaves

Filtration

Physical removal from liquid or gas. Sterilize solutions denatured by heat. i.e. Antibiotics, injectable drugs, amino acids, vitamins, etc.

Gas

Formaldehyde, glutaraldehyde, ethylene oxide. Toxic chemicals (require gas chamber)

Ethanol

Denatures proteins and solubilizes lipids. Antiseptic used on skin

Isopropanol

Denatures proteins and solubilizes lipids. Antiseptic used on skin

Formaldehyde

Reacts with NH2, SH and COOH groups. Disinfectant, kills endospores

Tincture of iodine

Inactivates proteins. Antiseptic used on skin

Chlorine gas

Forms hypochlorous acid (HCLO) – strong oxidizing agent. Disinfectant, drinking water, general disinfectant

Silver nitrate

Precipitates proteins. General antiseptic. Used in eyes of new borns

Mercuric chloride

Inactivates proteins by reacting w/ sulphide groups. Disinfectant, occasionally used as antiseptic on skin endospores

Detergents

Inactivates proteins by reacting w/ sulphide groups. Skin antiseptic and disinfectant

Phenolic compounds

Denature proteins and disrupts cell membranes. Antiseptic at low concentrations and disinfectant at high concentrations

Ethylene oxide gas

Alkylating agent. Disinfectant used to sterilize heat-sensitive objects

Chemotherapeutic agents

Synthetic agents that treat microbial or viral disease

Antibiotics

Chemical of natural origin that kills or inhibits growth of other cell types

Mycoplasma

Smallest known free-living organisms. 0.15-.03um. No cell wall. Shape varries from coccoid to long filaments. No peptidoglycans. Resistant to drugs that attack the cell wall. Cell wall contains sterols. Membrane proteins are structural, catalytic and immunological. Cytoplasm only contains ribosomes. Genome is 0.5-1x10⁹ Daltons. Smallest capable of self reproduction. Binary fission or filamentous process of reproduction. Looks like fried eggs under microscope (except M. pneumoniae). Colonies are small 600um in diameter. Require a rich growth medium w/ sterols and serum proteins. Has a unique attachment organelle

Filamentous reproduction process

Process in Mycoplasma sp in which genomic reproduction occurs at a pace exceeding cytoplasmic replication. Cell elongates and eventually fragments into many cells.

Primary atypical pneumonia

M. pneumoniae

Non-gonococcal urethritis

M. genitatlium

NGU

U. urealyticum

M. hominis

Stillbirth, Spontaneous abortion, infertility

L-form

Cell that has lost ability to produce cell wall, but that had a cell wall in at least one stage of life. NOT MYCOPLASMA. No sterols are present.

Ricketsiae

Obligate intracellular pathogens. Zoonotic except for Coxiella burnetli. 0.3-.05um in diameter. 0.8-2um long. Closely related to Gram(-). Have two membranes (CM and OM). Have D-aminopimelic acid. Part of arthropod intestinal flora. Not all have O-antigen (no LPS). Can not be cultivated on agar since they need host cells. Multiplication is slow. Binary fission, growth leads to host cell lysis.

Ricketsiae diagnosis

Macchiavello stain and Castaneda stain both stain organism against background, Giemsa stain just stains organism. Confirmative test is serological Weil-Felix reaction. Agglutinins in serum against proteus strains. Shared antigens: alkali stable polysacc haptens. Complement fixation test gives positive results 14 days into infection. Indirect fluorescent antibody test (Ehrlichiosis) detect IgM and IgG against Rickettsia

Chlamydiaceae

0.2-0.7um in diameter. Non-motile, coccoid. Originally thought to be viruses. Obligate intracellular pathogens. Can not generate ATP. Zoonotic infections between birds and men. Acquired via direct contact or via respiratory tract. Have two membranes, but no muramic acid/peptidoglycan

Chlamydia trachomatis transmission

Diseaase: trachoma, inclusion conjunctivitis, urethritis, cervicitis, ophtalmia neonatorum, Myocarditis, Lymphogranuloma venereum, Atherosclerosis, Neonatal pneumonia

C. penumoniae

Bronchitis/pneumonia/sinusitis via bird to human transmission. Can also cause atherosclerosis

C. psittaci

Meningopneumonitis, hepatic and renal dysfunction, conjunctivitis, abortion, and endocarditis. Transmitted from birds to humans

Chlamydia developmental forms

2 forms: elementary bodies and reticulate body/initial body. Dormant phase (EB)--> elementary body enter cell and metabolize --> reticulate body formation (8 hrs) --> reticulate bodies mature --> form EB in 24-48 hrs --> release from host cell as EB

Lab diagnosis

Isolation from infected tissue: cytoplasmic inclusion bodies in infected cells. Serological: microimmunofluorescent tests (anti-chlamydia Antibodies). Direct immnofluorescence: conjugated monoclonal Ab, complement fixation/fluorescent antibody test: rising titer Ab. Frei test: delayed type skin reactiojn (type IV hypersensitivity)

Louse-borne

European epidermic typhus

R. Prowazekii

OX-19

Brill's disease

R. Prowazekii

Negative

Trench fever

Bartonella quintana

Negative

Flea-borne

Endemic murine typhus

R. typhi

Wild rodents

OX-19

Cat scratch fever/Bacilliary angiomatosis

Bartonella henselae

Domestic cat

Unknown

Mite borne

Scrub typhus

R. tsutsugamushi

Wild rodents

OX-K

Rickettsial pox

R. akari

House mice

Negative

Fly borne

Oroyo fever/Verruga peruana

B. bacilliformis

Unknown

Tick borne

Rocky mountain spotted fever

R. rickettsii

Dog, rodents

OX-19, OX-2

North asian tick typhus

R. siberica

OX-19, OX-2

Fievre boutonneuse

R. conorii

Dog, rodents

OX-19, OX-2

Queensland tick fever

R. australi

Marsupials, rodents

OX-19, OX-2

Q-fever

Coxiella burnetii

Cattle, sheep, goats

negative

Spotted fever

R. rhipicephali

Dogs

Unknown

Ehrlichiosis

E. canis

E. chaffeensis

Dogs

dogs

Negative

negative

DNA/RNA

+

-*

+

+

+

Obligate intracellular pathogen

-

+

-*

+

+

Peptidoglycan in cell wall

+

-

-

+

?

Growth on agar plate

+

-

+

-*

-*

Contain ribosomes

+

-*

+

+

+

Sensitivity to antiB/interferon

+/-

-/+

+/-

+/-

+/*+

Binary fission

+

-

+

+

+

Bacterial chromosomal replication

Initiation, elongation and termination. Bi-directional and semi-conservative. Helicase unzips DNA, RNA primer synthesized, RNA primer gives initiation site of synthesis, formation of replication fork, DNA Polymerase III attaches at origin, DNA synthesized 5'->3', now have 2 strands, DNA Polymerase I replaces primer w/ DNA

Okazaki fragments

Short fragments made on lagging strand

Non-chromosomal replication

1 strand nicked and it forms a unidirectional point of origin for replication

Operon

A set of genes grouped together for regulation purposes. IPOABC where I=initiator, P=promoter, O=operator and ABC are genes. Regulate genes include diphteria toxin, cholera toxin, fimbriae of uropathogenic E. coli

Chromosomal CtxR

Controls operon for diphtheria toxin (beta-phage encoded)

Lac operon

Lactose binds to repressor causing it to fall off. Repressor bound to operator region otherwise. Low cAMP levels no binding with CAP, so no transcription. High cAMP will bind w/ CAP leading to transcription.

Trp operon

Low level of trp, no binding to repressor, gene transcribed.

Mutation

Permanent, heritable change in genetic information. Can be natural (mistakes in replication) or chemical (chemical acting to force change)

Wild type

Non-mutated form of a gene

Missense mutation

Mutation changes AA sequence.

Nonsense mutation

Mutation causes AA gene to be changed to stop codon

Silent mutation

Mutation has no effect on AA sequence

Back mutation

A mutant form reverts back to original wild-type

DNA polymerase III

Responsible for DNA replication. Can remove and replace defective genes.

Acquisition of genes

Plasmids via conjugation, loose DNA via transformation, bacteriophage via transduction, jumping genes

Conjugative plasmid transfer

F-factor encodes F-pilus needed for conjugation. F-factor gene is encoded for on a plasmid. This plasmid also contains transfer genes.

F+ cells

Cells possessing f-factor gene

Hfr cell

High frequency of recombination cell. F factor is on chromosome.

Transformation

Can be discriminatory (species specific) or indiscriminatory. Haemophilus is discriminatory and pneumococcus is not. Uptake by DNA binding proteins on cell wall. Cells w/ binding protein are considered competent

Prophage

Bacteriophage genes integrated into host cell DNA. Phage encorporates the wrong part of host DNA into phage head. Generalized if any part of host chromosome is packaged. Specialized if a certain area is selected for (those around prophage genes).

Transposon

Jumping genes. Contain sequences for excision and reinsertion into the chromosome. If inserted into other gene, inactivate that gene.

Recombination

Homologous (between similar DNA sequences), can result in drug resistance, virulence factors. Can occur w/ transposons.

Pathogenicity island

Virulence genes usually localized on chromosome

Beta phage

Gives virulence to C. diphtheria

Antisense DNA

Binds specific sites on mRNA that are therapy targets and block translation. Can not be used for non-functional genes (CF, sickle-cell)

Triplex DNA

Insert third strand to prevent transcription. Early stages of technology

Quarternary ammonium compounds

Found in mouth wash. Cetylpridinium chloride. Antiseptic

Resistance mechanisms

Drug inactivation, altered uptake, altered target

Krby-bauer method

Disk diffusion method. Plate is incubated and zone of inhibition measured. Inhibition zone is compared against a standard.

Inhibition zone

Area of no bacterial growth

Broth dilution method

Dilution of drug in liquid medium and inoculated w/ organism. Determine minimum concentration (MIC) of drug needed to suppress growth and minimum bactericidal concentration (MBC). Agent is bactericidal if MBC < 4MIC

Amphenicols

e.g. Chloramphenicol. Block attachment of amino acids to 50S subunit. Bacteriostatic. Resistance by modifying drug via enzymes. Limited applications.

macrolides

e.g. Erythromycin. Prevent peptide elongation by binding 23S subunit of 50S subunit. Bacteriostatic. Good intracellular penetration. Resistance by rRNA methylases

Aminoglycosides

Inhibit 30S subunit to make ribosome unavailable. Bactericidal. Useful against Gram(-) infections. Resistance by modifying enzymes and altered uptake.

Tetracyclines

Block access of tRNA to mRNA-ribosome complex. Bacteriostatic. Treatment of choice for Rickettsial infections because it can enter cells. Resistance to drug by rapid drug efflux, altered target and modifying enzymes

Lincosamides

Bacteriostatic. Binds 50S subunit to interfere w/ peptidyl transfer. Lincomycin, clindamycin (chlorinated derivative of lincomycin). useful in treating severe anaerobic infections.

Rifamycins

e.g. Rifampicin (sweat and saliva turns orange). Binds to RNA polymerase and blocks mRNA synthesis. Broad spectrum including M. tuberculosis. Bactericidal. Restricted use to mycobacterial infections. High affinity for bacterial polymerases v. human polymerase. Affinity for plastics. Useful in treatment of infections involving prostheses. Resistance via altered RNA polymerase

Nitroimidazoles

Treat anaerobic bacteria and some protozoa (Giardia lamblia, Entaemoeba coli). Bactericidal. Forms toxic metabolite w/ anaerobic metabolism. Resistance rare: altered uptake or decreased cellular uptake

Polymyxins

Colistin (polymyxin E), polymyxin B. limited spectrum (gram(-) bacteria); bactericidal. Free aa act as cationic detergents to destroy integrity of phospholipid bilayer. Nephro and neuron toxic. Applications include wound irrigation and bladder wash-out. Resistance via altered uptake/membrane structure

Cycloserine

Structural analog of D-alanine. Blocks D-alanyl D-alanine peptide synthesis. Inhibits peptidoglycan subunit synthesis. Active against all mycobacteria. Second drug for TB

Bacitracin

Prevents dephosphorylation of phospholipid carrier (bactoprenol): no regeneration of carrier. Active against Gram(+), Staphylococci, Streptococci. Only topical use

Glycopeptides

Vancomycin and teicoplanin. Large molecules; have difficulty penertraing Gram(-) cell wall. Narrow spectrum bactericidal. Complex w/ D-alanyl-D-alanine residues of cell wall precursor; inhibit transglycosylation. Incorporation into peptidoglycan precented. Will not work againt G- or mycobacteria. Use against G+ and rods resistant to beta-lactams. Resistance in staphylococci is rare. Applications restricted to severe life-threatening infections

Beta-lactams

Contain beta-lactam ring in structure. Penicllins, cephalosporins, monobactams, carbapenems. Active only on growing cells. Bactericidal. Do not work on intracellular species or on species w/o cell wall. Less active against G- bacteria. Resistance via altered target, altered uptake and drug inactivation.

Penicillins

Structurally similar to D-alanine D-alanine. Inhibits activity of transpeptidases (penicillin binding protein) preventing the formation of cross-links. Cell wall can not hold cells and cell will burst

Cephalosporins

Cephalxin, cefaclor. A Beta-lactam. Similar to penicillin but resistant to penicillinases. More effective against G- organisms. Different generations w/ each subsequent generation more resistant to bacterial resistance and more active against G- bacteria

Beta-lactamase

Destroys beta-lactams thus protecting bacteria from drug activity. Staphylococci and other G+ bac. Excrete them extra-cellularly. More drug, more B-lactamase produced. G- bacteria have constitutive production of B-lactamase thus enough drugs will overwhelm B-lactamase

Beta-lactamase inhibitor

Clavulanic acid, sulbactam, tazobactam. Synergizes w/ beta-lactams to kill bacteria

Monobactams

Aztreonam. Synthetic. Single ring. Inhibits transpeptidase. Bactericidal. Only useful in G- bacteria. Pseudomonads and E. coli. Low toxicity

Carbapenems

Primaxin. Penicillin-like. Inhibits transpeptidase. Bactericidal. Resistant to most beta-lactamases. Causes cell elongation and lysis. Most potent beta-lactam against anaerobes.

Sulfonamides

Sulfa drugs. Completely synthetic. Sulfamethizole. Sulfamethoxazole. Structure mimics PABA. Used by bacteria to synthesis folic acid. Faulty folic acid made. Competes for active spot of THFA which is needed to make purines and pyramidines. High affinity for bacterial enzymes. P. aeruginosa, enterococci, anaerobes are resistant. Plasma encoded gene transfers resistance.

Trimethoprim

Acts synergistically w/ sulfonamides. Bacteriostatic. Pyramidine analogue. Active against UTI and Salmonella typhi

Quinolones

Analog of nalidixic acid. Inhibits gyrase activity. 3 generations. Specific to bacteria. Mammalian topoisomerases unaffected. Can cause toxic effects on cartilage decelopment, so can not be used on children. Resistance is chromosomally-mediated. Altered DNA gyrase subunit structure. Can permeate intracellularly.

Isonaizid

Isonicotinic acid hydrazide. Only effective against mycobacteria. Inhibts mycolic acid synthesis. Usually used in combination w/ other antimycobacterials

Ethambutol

Used against Mycobacterium tuberculosis. Interferes w/ RNA synthesis. Mycostatic. Resistance develops quickly, so used w/ other drugs.

Acute infection

Symptoms develop rapidly, but last only for a short time

Adhesin

Molecule present on a microbial cell that is responsible for enabling adhesion of organism to a host cell or to a surface

Antigenic variation

Alteration of the antigen surface components in order to evade the immune responses of the host.

Chronic infection

Symproms develop slowly and illness is likely to reoccur or continue for long periods. Symphilis, tuberculosis

Colonization

The multiplication of an organism following adhesion to a tissue or a surface

Compromised individual

Individual w/ one or more defects in there natural defenses

Neutropenic patients

Highly susceptible to aspergillosis

Aspergillus fumigatus

Oppurtunistic parasite. Infects immunocompromised individuals

Exogenous infection

An infection due to an organism acquired from an external source such as food, water, animals or sexual contact.

Endogenous infection

An infection due to a member of the normally non-pathogenic microflora. E. coli cystitis and Candidiasis

Infection

Invasion/colonization by pathogenic microorganisms

Microflora

Those organisms present at a particular anatomical site

Nosocomial

Acquired in a hospital

Pathogen

A disease causeing organism

Pathogenicity

Ability of a microorganism to cause disease by overcoming the defenses of the host

Primary infection

Acute infection that causes the initial illness

Secondary infection

Caused by opportunistic pathogen after primary infection has weakened defenses. Influenza followed by Streptococcal pneumonia

Systemic infection

Infection that spreads throughout the body of the individual

Virulence

Degree of pathogenicity of an organism.

Sterile locations

Blood, spinal fluid, organs

Acquisition of normal flora

Exposure at birth (changes w/ diet); environment (air, dust, food, water, human contact)

Survival of flora

Receptor availability; existing flora; evasion/survival of extreme unfavorable conditions

Normal flora pathogenicity

Microflora spreads to other body site (intestinal perforation, tooth extraction)

Non-normal flora pathogenicity

Changes in normal flora, changes in local environment, or deficiencies in immunity can lead to infection w/ non-normal flora pathogens

Ininfectious process

Entry, adhesion, invasion, dissemination, growth/multiplication, dissemination, release/transmission

GI tract infections

Faecal oral transmission; localised (diarrheal disease) or systemic (Hepatitis A)

Genital tract

Local lesions (HSV) or may spread e.g. Meningitis due to HHV

2ndary sites of infection

Delayed symptoms, incubation period, viral tropism for specific cell types and tissues

Viremia

Rash due to infection of epithelial cells (contains infectious virus)

N. meningitidis

Blood borne organism that infects edothelial cells fo cerebral vessels and crosses blood brain barrier. Can be released from endothelial cells into CSF at choroid plexus

Rabies

Axonal migration from peripheral nerve endings to CNS

Fetal infections

Virus from maternal circulation can infect placental cells, fetal circulation and tissues. This can lead to death or developmental abnormalities

Adhesion

Highly specific molecular interactions. Causes changes in bacterial phenotypes and host cell behaviour. Can adhere to skin, blood vessels and artifical surfaces such as titanium hip joints. Can occur via hydrophobic interactions, cation bridging, receptor-ligand binding. Can be directly to bilayer or surface receptors, or indirect via host molecules bound to cell. Receptors and ligands can be composed of proteins, polysaccharides, glycoproteins, glycolipids.

Ligands

Bacterial structure involved in adhesion. All bacterial cell surface molecules can be involved in adhesion, but some molecules may exist specifically for that purpose

Fimbriae

Multisubunit appendage involved in adhesion. Pili are composed of protein and carbohydrate

Diptheria

Infection of oral epithelium caused by C. diphteriae. Tissue specific

Gonotthoea

Urogenital epithelium. N. gonorrhoeae. Tissue specific

E. coli

Type I pili interact w/ mannose receptors on epithelial cells

Streptococcus pyogenes

M protein aa sequence overlaps w/ host components. Mediates attachment to host epithelial cells and resistance against phagocytosis (important in pathogenesis). M protein binds to C4BP (a regulatory of complement activation) w/ RCA still active. Bacteria is covered by compliment inhibitor thus blocking phagocytosis. Produces hyaluronic acid capsule that is antigenically identical to ground substance

Vibrio cholerae

Specific adhesion pilus (toxin coregulated pilus TcpA). Enables colonization of intestinal mucosa. Synthesis controlled by same regulatory system as for cholera toxin. Mutants lacking TcpA are avirulent

Viral adhesion

Receptor specificity narrowing target organs (increased specificity)

Hepatitis B

Increased tropism for liver. Chronic infection w/ virus continually detectable at low levels. Mild or no clinical symptoms

Influenza

Adhesin: Haemagglutinin; receptor neuramic acid. Tropism for upper respiratory tract. Antigenic switching occurs with haemagglutinin and neuraminidase

HIV

Adhesin: envelope of gp120 proteins. Receptor CD4 proteins

Rhinovirus

Adhesin: Capsid protein; receptor intercellular adhesion molecules (ICAM-1)

Auto-immune disorders

Immune system is unable to distinguish clearly between self and non-self. Loss of tolerance.

Reiter's syndrome

Complication of shigella infection that leads to joint inflammation

Post-streptococcal rheumatic fever

Caused by certain strains of Group A Streptococci (GAS). Streptococcal pharyngitis can be followed by acute rheumatic fever. Streptococcal antigens cross react with heart muscle and valvular connective tissue. Evoke cross reactive T cells

Post-streptococcal glomerulonephritis

Can occur following pharyngitis, impetigo, and some other streptococcal infections. Characterized by hypoalbuminemia and salt retention. If antigen is in excess, formation of antibody-antigen complexes. Cross reaction between complexes and glomerular tissue. Results in inflammation and tissue damage

Systemic inflammatory response syndrome

The cross-reaction between antibody-antigen complexes and glomerular tissue

Systemic inflammatory response syndrome

Endotoxic shock, septic shock, sepsis. Infectious and non-infectious causes. In response to G- bacteria endotoxin or in response to peptidoglycan, teichoic acids, exotoxins, e.g. TSST-1, fungal cell wall components

Invasion

Invasive organisms usually have longer incubation period. Invasion facilitated by enzymes (collagenase and hyaluronidase). Invasins induce endocytosis by host cells

M. Tuberculosis

Survives within phagocytic cells

S. typhimurium

Causes gastroenteritis. Can survive in phagocytic cells

B. burgdorferi

Causes lyme disease. Can invade epithelial cells

Poliovirus

Produces lytic infection. Virus overruns cells and kills them off. Crosses blood-CSF junction (meninges or choroid plexus)

Transformation

Oncogenesis. Irreversible. Stable intergration of viral DNA into host DNA. Host cells exhibit altered cell surface, metabolic functions and growth and replication patterns.

Cell fusion

Results in large multinucleate cells. Herpes viruses and paramyxoviruses.

Salmonella typhi

GI tract epithelia is site of epithelial invasion

Treponema pallidum

Urogenital tract is site of epithelial invasion

Mycobacterium tuberculosis

Respiratory tract is site of epithelial invasion. Forms granuloma that is immunosuppressive

Staphylococcus aureus

Skin is site of epithelial invasion. Protein A binds antibodies for evasion of acquired immunity.

sIgA evasion

By production of glycosidases or sialidases. Proteases. IgA-binding proteins

Lactoferrin-binding protein

Binds antibacterial protein allowing for evsion.

Efflux pumps

Removes antibacterial peptides from bacterium.

Cytokine

Protein or glycoprotein acting as an intercellular signal. Overproduction can overwhelm system with multiple signals.

Modulins

Molecules capable of stimulating cytokine production. LPS, PG, LTA, lipoproteins of mycobacteria

Virokines

Cytokine-like proteins. Affect IL-10 (imp. In controlling inflammatory response)

viroreceptors

Viroreceptors = receptors for cytokines

Cholera toxin

Inhibits cytokines. Inhibits IL-12 secretion by APCs

capsules

Protein or polysaccharide that impairs phagocytosis. Adhesion by phagocytes is prevented. Capsule produces are Streptococcus pneumoniae and Haemophilus influenzae

Leukocidins

An exotoxin that kills neutrophils and macrophages. Produced by Staphylococci and Group A streptococci (including beta-hemolytic strep). Can be released into surrounding environment or into phagocyte

Leukotoxins

exotoxins that acts to kill neutrophils and macrophages

Proteases

Degrade sIgA. May also inhibit/inactivate complement

Psuedomona aeuruginosa

Produces an elastase that inactivates C3b and C5a

Herpesvirus

Capable of blocking MHC Class I/II-dependent antigen processing

Listeria monocytogenes

Listeriolysin can impair antigen processing

Superantigens

Highly potent protein exotoxins. Toxic shock syndrome toxin

HBV

Long term infection of cells (persistant, latent infections). No adverse effects on cell viability.

Pseudomembranous colitis

Results by the colonization of pathogenic organisms when the normal microflora has been disrupted

Neutropenia

Granulocyte abnormalities that leads to an innate immune deficiency

Specific immune deficiency

Cell mediated immunity abnormalities as with AIDS

Hyaluronidase

A toxin that allows for the spread of a pathogen

HSV

Spreads via nerves. Occult persistence. Intermittent flare-ups

Haemophilus influenzae

Spreads via CSF. Crosses blood-CSF barrier through meninges or choroid plexus

Blood dissemination

Hepatitis B and B. anthracis spread via plasma. HSV, listeria spread via mononuclear cells

Lymphatic dissemination

Spread from tissue fluid into lymphatic capillaries. Yersinia pestis, measles, polio and HIV

Neiseria

Pilin subunits undergo antigenic switching

Carrier

Someone who can harbor and transmit a pathogen. May be asymptomatic. i.e. Women w/ Gonorrhea and early HIV

Francisella tularensis

10 to 50 cells is enough to establish infection --> tularemia

Salmonella

Need 10⁶ cells to establish foodborne infectious disease

Host factors influencing infection

Age, sex, nutritional status, immune status, receptor sites (genetic)

Sites for shedding

Skin: from lesions such as warts, vesicle fluid (impetigo). Respiratory tract: infected droplets (influenza, tuberculosis). GI tract: faecally (salmonellosis, Norwalk virus). Body fluids: blood, milk (HIV, listeriosis)

Transformed cell

Viral DNA is integrated into host cell

Fungaemia

Sepsis due to fungal infection

Angioinvasive aspergillus

Causes necrosis of the lung walls and bleeding

Fungal infection consequences

Mild to asymptomatic. Limited by immune responses. Delayed type hypersensitivity reaction. Chronic infection more common than acute. Often difficult to treat

Proteases

Capsules

Toxins (e.g.) aflatoxin

Keratin-digesting enzymes

Ability to grow at > 37 degrees

Candida albicans

Cryptococcus neoformans

Aspergillus flavus

Dermatophytes

Systemic fungi

Cholera toxin

A:5B subunit toxin. Regulated by pH, temperature and osmolarity. Binds G-protein of adenylate cyclase complex causing stimulation block --> unregulated cAMP. Stimulates secretion of Cl^- and H₂O while inhibiting NaCl absorption --> severe fluid loss and electrolyte imbalance.

Toxin producing organisms

Bacillus anthracis, Bordetella pertussis, Clostridium botulinum, Clostridium tetani, Corynebacterium diphteriae, Escherichia Coli, Listeria monocytogenes, Pseudomonas aeurginosa, Shigella dysenteriae, Staphylococcus aureus, Streptococcus pyogenes, Vibrio cholerae

LPS toxins

Only act as toxins under certain circumstances. Endotoxins. LPS component of the outer membrane of G- bacteria. Released following bacterial cell death and lysis. Capable of activating almost every immune mechanism. One of the most effective immune stimuli known. Action of endotoxin is concentration dependent. Low concentrations canlead to fever, inflammation, vasodilation, increased antibody synthesis. Effect at high concentrations include shock and intravascular coagulation. Activation of complement, macrophages, and B-cells (via IL-1).

Protein toxins

Secreted into extracellular environment. Specificity varies. Exotoxins. Very potent

Vibrio cholerae

G- that produces an exotoxin.

Class I exotoxin

Superantigen toxins. Binds membrane of host cell surface. (TSST-1). Interact non-conventionally w/ immune cells. Results in direct stimulation of immune response (VERY POTENT). Can activate up to 20% of T-cells (2000X as many). Produced by staphylococcal and streptococcal species. Responsible for much of pathogenesis/toxicity

Class II exotoxin

Membrane damaging. (phospholipases, pore-formers).

Class III exotoxins

Intracellular (diphtheria toxin, cholera toxin). Entry by receptor binding, receptor mediated endocytosis (RME), and internalization. Composed of Active and Binding subunits. Common mode of action: ADP-ribosyltransferase.

Phospholipases

Class II exotoxin. e.g. Lecithinase (clostridia). Causes enzymatic damage by utilization of phosphatidylcholine. Eliminates host defences and creates a nutrionally rich environment

Pore formers

Alpha-toxin of S. aureus. Pores are highly fortified protein structures. Resistant to protease and detergents. Cell death by osmotic lysis. Also called channel forming toxins (CFTs).

Diphteria toxin

Encoded by beta-phage. A:B subunit toxin. Must be proteolytically be cleaved to become activated. Single molecule sufficient for cell death. Inhibits protein synthesis by converting NAD⁺ + EF-2 --> ADPR-EF-2 + nicotinamide + H^-.

Neurotoxins

Tetanus and botulinum toxins. Act intracellularly. Single polypeptide. Proteolysis and disulfide bond reduction. Binds to ganglioside receptors. Peptidases block release of neurotransmitters and inhibitory mediators.

Tetanus toxin

Clostridium tetani. Bacteria remains localized, but toxin spreadss. Binds presynaptic membranes of motor neurons. Migrates to spinal cord and brain stem --> degrades synaptobrevins. Inhibits release of inhibitory neurotransmitters such as GABA and glycine. Incubation of ~ 1 week prior to symptoms.

Botulinum toxin

Clostridium botulinum. Activated by intestinal proteases. Toxin carried in blood to neuromuscular junctions at peripheral nerve endings. Blocks acetylcholine relaxing muscles irreversibly. Can result in respiratory arrest. Symptoms include diplopia, dry mouth, pupillary abnormalities, ptosis, dysphagia, dysarthria. Usually occurs 4-36 hours after ingesting toxin

Streptokinase

Produced by many group A beta-hemolytic streptococci. Plasminogen-->plasmin-->fibrin-->fibrin breakdown. Useful for treatment of pulmonary emboli and coronary thromoses

Indogenous pyrogens

IL-1 and TNF. Release can be caused by endotoxin.

High endotoxin concentrations

Systemic inflammatory response syndrome (SIRS). Hypotension, disseminated intravascular coagulation (DIC).

Limus test

Use amoebocytes from horseshoe crab. Endotocin --> degranulation and lysis of amoebocytes. Degree of reaction measured spectrophotometrically

Toxoid

Chemically modified toxin. Retains immunogenicity while losing toxicity

Antitoxin

Antibody produced against toxin. Must be administered rapidly or will be ineffective

Serum sickness

Body producing antigens against forein antibodies (i.e. horse antibodies for tetanus)

Biofilm

Bacteria adhesed to a surface w/ a protective mucus layer. Resistant to antibiotics and WBC attack.

Planktonic

Free floating bacteria

Sessile

Bacteria on biofilm. Act as reservoir for planktonic form

Sessile killing dose

1000X planktonic killing dose

Colonization

Refers to the formation and growth of bacteria on a surface. All synthetic implants can be colonized. Middle ear is normally colonized. Prostate by age 50 is colonized in 100% of males (in a trial),

Implants

Must be removed to resolve infection

Nosocomial sites

ICU pneumonia, sutures, exit sites, arteriovenous shunts, schleral buckles, contact lenses, urinary catheter crystitis, peritoneal dialysis peritonitis, IUDs, endotracheal tubes, Hickman catheters, mechanical heart valvles, vascular grafts, biliary stent blockage, orthopedic devices

Cystic fibrosis

Provides ground for biofilm growth in lungs

Natural biofilm infections

Dental carries/peridontits, necrotizing fasciitis, osteomyelitis, endocarditis, pneumonia Cystic fibrosis

Furanones

Trials suggest that it may be effective in clearing biofilm infections

Acute infection

Brief/severe infection

Anchorage dependent

Can not grow in suspension. Tumor cells are anchorage independent

Bacteriophage

Virus that infects a bacterium

Budding

Branching off of cell. Slowly leaves cell taking part of cell membrane (envelope).

Capsid

Protein coat or shell surrounding nucelic acid. Coded for by protemers

Capsomere

Noncovalent aggregations of protomers; usually visible by electron microscopy

Cell culture

The maintenance or growth of dispersed cells after removal from the body, commonly on a glass surface immersed in nutrient fluid. Primary cell line, directly from the animal. Secondary cells are adapted to gorwth medium (may be different).

Chronic infection

Long term low grade infection

Complementation

Complex virus

Conditional lethal mutant

Deletion mutant

Mutation in which amino acids (nucleic acids) are lost. Can be used for attenuation

Disseminated infection

Eclipse phase

Infectious virus cannot be recovered from infected cells; uncoating has occurred and viral macromolecular synthesis is underway. Time from viral entry to production of mature virus in cytoplasm.

Ectomelia

Envelope

Substance surrounding a virus. Not naked (proteins/nucleic acid).

Extra cellular virus

Has no metabolism.

Filterability

Things that will pass through bacterial filters

Genome

Complete set of genes for an organism

HeLa cell

Cervicle cancer cells isolated from a patient. Continuous immortalized cell line

Hexon

Group of protomers grouped into 6 sided figure

ID50

A quantal assay. Infectious dose 50. What dilution will kill 50% of population.

TCID50

LD50

Icosahedral

Type of viral structure. 5-fold axis of symmetry through corners; 3-fold through center of each face; 2-fold through middle of edge (5:3:2 = pentagon:triangle:line)

Inclusion

Interferon

Warning system for surrounding cell saying: “I'm infected”. Other cells will then be protected. Successful viri must have a way to overcome interferon.

Interference assay

Intracellular virus

Iwanowski

LCM model infection

Latent infection

Viral genome can be detected but infectious virions are not produced except in certain conditions (Herpes, adenovirus). Herpes stays as DNA only

Latent phase

Progeny virus accumulates intracellularly or extracellularly. Can see free virus being released; different families have different time periods. Time from viral entry (mature virus) to production of mature virus

Local infection

Marker rescue

Mosaic envelope

Multiplicity reactivation

Nucleic acid

RNA/DNA. Genetic material

Nucleocapsid

Enveloped virus. Capsid in a lipid bilayer

Nucleocore

Reserved for structures found within complex: virion & typically is not used to describe helical nucleocapsid; (shell/capsid containing nucleic acid). Capsid in a protein coat

Oncogenic virus

Virus capable of transforming a cell

One step growth cycle

Penton

5 protomers grouped together.

Penton fibre

Long viral glycoproteins found in the adenovirus. Attachment protein. Specific to the virus (i.e. Coded for by the virus)

Plaque

An area of clearing in a flat confluent growth of tissue cells. Plaque assay find regions of wholes in cell monolayer after virus has been added. (Virus particle enters and kills cells and neighboring cells). Non-permissive cells will not form plaques

Peplomer (spike)

Viral glycoproteins that produce or project from the envelope. Attachment protein. Can be used for viral identification. Can be used for diagnosis. H5/N2 strains are differentiated by peplomer structure

Pock

Embryonated agges. Used to distinguish pox. Chicken pocks will give many small hemorhages.

Prion

Infectious protein

Promotor

Protomer

Basic unit of viral capsid. Capsomeres are made of protomers. 3 protein subunits. Asymmetric.

Pseudo-tolerance

Recombination

Mostly occurs w/ DNA viruses. Retroviruses w/ proviral DNA

Reassortment

Like recombination, but in RNA. Segments assembled in incorrect order.

Scanning Electron-microscope

Able to visualize characteristics of viri. Does not distuinguish between virus and virion. Gives total number of particles not all of which are infective.

Target tissue

Cells w/ receptors for virus (cells that will be infected by virus) and will result in clinical disease upon infection

Topoinhibition

Transformation

Expression of certain viral genes in animal cells which alters morphological and biochemical properties characteristic of neoplastic cells or tumor cells. Transformed cells do not necessarilly produce tumors. NON-PERMISSIVE cell w/ DNA virus or RNA retrovirus

Transformation assay

detects “altered,” non-permissive cells. Morphology of transformed cells can change.

Transcapsidation

Genes from one virus, capsule from another virus

Viral hemagglutination

Allows u to get the viral concentration using adhesion to RBCs. Virus will cause RBCs to stick together. Virus must intrinsically be able to bind to RBCs. NON-Serological test.

Viral neutralization

Antibody binds to virus. Antibody is detected by attachment to the cell. Neutralization test tests only antibodies against a given species not the presence of that species. Serological test

Virus

Obligate intercellular parasites “filterable aents” which on their own are inert biochemical complexes. DO NOT GROW

Virion

Infective part of a virus. All parts needed to infect: protein/nucleic acid

Viroid

Infectious agents composed exclusively of circular single stranded RNA w/ regions of double strandedness. Causes disease in plants

Von Magnus phenomenon

No proof reading of viral nucleic acid leading to production of large quantities of defective and modified viri and also antigenic shifting.

Vector borne

Carried by a “vector” such as an arthropod. Has a transmitting agent

Replication

Particles produced from assembly of preformed components. Process leading to synthesis of progeny viral genomes

Adenovirus

dsDNA Naked, icosahedral virus. Penton fibers at vertices

Herpes virus

dsDNA enveloped icosaheddral virus. Projections or knobs on envelope

Paramyxoviruses

Class V. Has envelope and peplomer. Activity on one peplomer.. ssRNA, enveloped helical. Causes infections mainly in children

Orthomyxovirus

Segmented ssRNA, enveloped helical virus with peplomers (spikes)

Productive outcome

Infectious progeny are produced by permissive cells. 17 day old embryonic rat liver cell is susceptible to polio virus, but no 19 day old cell. 17 day old leads to productive outcome

Abortive outcome

No infectious progeny are produced; non-permissive cells may be susceptibile to infection but may not allow virion formation.

Retrovirus

The only RNA viruses with demonstrated oncogenicity

Cis activating retrovirus

Have no oncogenes but activate cellular oncogene in situ

Trans acting retrovirus

Have no oncogene but carry a viral transactivating protein

Pseudo-virion

Empty protein shell (not infectious)

Pox virus

Has thick protein coat.

Rotavirus

Most common viral infection uder age of 5 (childrens infection). Double capsid. Characteristic capsid can be used for identification

Tropism

Tissue affinity. Defines the capacity of a virus to infect a discrete type of cell. Used as classification until it was learned that viri can infect different tissues.

Hepatitis viruses

All infect liver and have same pathology

Viderae

Family of viruses. e.g. Herpesviderae.

Viriniiae

Sub-family. e.g. Lentiviriniae

Classification

Nucleic acid is the most important criteria for classifying bacteria. Enveloped/nonenveloped, size, shape, symmetry, capsid morphology

Hepatitis A

Is not destroyed by boiling water.

Small pox

Stable to radiation, thermal, pH.

Salmonella

Can cause eggs to smell by producing H₂S. Black deposit in air sac of boiled egg

Cytopathic effects

Things you look for when trying to determine type of infection, pocks, plaques, and transformation assays. Lysis, necrosis (cell death but no lysis), syncytium formation (multinucleated giant cells), vacuolation or inclusion body formation.

Neuraminidase

Digests peplomer subunit. Can then detect digested components.

Serological test

Much more sensitive. Other tests may not detect virus. Primary highly specific, but may not be detected. Immunofluorescence can improve detection.

Hemagglutination inhibition test

Antibody test. Add antibody to virus, add RBCs. If no agglutination, antibody is for added virus. 4X increase in serological titier to serologically confirm a disease. Serological test

Host range

Defines the types of cells, tissues species that can be infected and in which the virus can multiply

Portal of entry

Cells initially infected where a virus enters a host

Target cells

Cells which, when infected results in clinical disease. May not be portal of entry

Syncytium formation

Herpes virus, HIV can cause this. Giant cell formation

Restrictive

Cell may become permissive, but virus must wait

Cytocidal infection

Infection that leads in cell death (lytic infection)

Persistent infection

Non-lytic. Host immune response must be avoided. Hepatitis B, Measles, HIV

Parvoviridae

DNA virus that do not transform cells

Papillomaviridae

Do not need to integrate into host cell genome

Reverse transcriptase

Used by retro viruses to produce DNA. Necessary for transforming RNA viruses

Transduction

Transfer of genetic material from one host to another by a virus.

v-oncogenes

Cellular sequences acquired by a retrovirus and can be transferred to host cells (the source gene)

Adsorption

(attachment) Specific binding of a host virion protein to a host cell surface (receptor). Can take 6 steps before penetration can occur.

Penetration

Energy dependent stage that occurs rapidly after attachment leading to the introduction of viral genetic material, usually accompanied by at elast some viral proteins, into the interior of the cell

Membrane-envelope fusion

Viral envelope fuses w/ host cell membrane

Viropexis

Used by a naked virus

Receptor-mediated endocytosis

Method of viral entry. Used by a virus with a capsid

Uncoating

Term applied to events that occur after penetration and that set the stage for the viral genome to express its functions. Usually involves removal of certain viral proteins

Viral locations

RNA viruses stay in cytoplasm, DNA viruses go into nucleus

Pox virdaes

DNA virus that stays in cytplasm

RNA virus that goes into nucleus

Assembly/maturation

Assembly of virion components into virions; maturation events involve structural changes that occur during or following assembly.

Egress

Release of virus from cell

Baltimore classification

Based on relationship between the viral genome and the mRNAs used for translation of viral proteins.

Positive sense

Positive polarity. mRNA sense of RNA. RNA that is transcribed directly

Negative sense

The complimentary strand of positive sense RNA. No enzymes exist to turn negative sense RNA in cell. Virus must bring RNA-dependent RNA polymerase w/ it.

Virus associated enzyme

Virus brings pre-made enzyme with it

Class I virus

DNA virus used to synthesize mRNA to make immediate early proteins, then early proteins which can make progeny DNA which can then make late proteins which will make the progeny VIRUS.

Papovaviridae

Class I ds, circular DNA

Adenoviridae

Class I ds, linear DNA + 55S protein

Herpesviridae

Class I ds, linear DNA

Poxviridae

Class I ds, linear DNA w/ closed ends. Does NOT go into the nucleus. Brings its own enzymes.

Paroviridae

Class II ss, linear DNA. 50% of viral progeny are positive strand and 50% are negative strand

Circinoviridae

Class II ss, circular DNA. Can cause tt hepatitis.

Class II virus

Single stranded DNA. Virus DNA (+strand) --cellular proteins--> double stranded DNA --> mRNA --> virus proteins. dsDNA + virus proteins --> progeny virus.

Class III

Double stranded RNA. Double capsid virus. Virus RNA –virion enzyme--> mRNA --> virus proteins. viral RNA --> progeny RNA. Viral protein + progeny RNA --> progeny virus

Reoviridae

Class III, linear RNA. Induces interferon.

Reovirus

10 segments.

Rotavirus

11 segments. Most common viral diarrhea under the age of 5.

Class - IVa

Virus RNA --> poly-protein --> protein cleaved --> structural and enzymatic components. Virus Enzymatic proteins duplicate RNA. Only positive strand is encapsulated. Must become double stranded to replicated; therefore, interferon can be triggered.

Picornaviridae

Class IVa, +, ss, linear RNA

Caliciviridae

Class IVa, +, ss, linear RNA. Hepatitis E

Flaviviridae

Class IVa, +, ss, linear RNA. Yellow fever, dengae, hepatitis C

RNA dependent RNA polymerase

Makes complement strand which can then make more original strands.

Class IV b

Original virus RNA codes for enzymes to make complement strand which can then make mRNA to make viral structural proteins to make progeny virus.

Togaviridae

+, ss, linear RNA

Coronaviridae

+, ss, linear RNA

Class V

Negative polarity RNA. Virion enzymes make mRNA which codes for viral proteins that can then make more -pol RNA to be packed.

Orthomyxoviridae

-, ss, linear, 8 segments. influenza

paramyxoviridae

-, ss, linear, Vaccination possible

rhabdoviridae

-, ss, linear Rabies

Filoviridae

-, ss, Ebola, marberh, ambisense

Bunyaviridae

-, ss, 3 segs. Hanta virus

arenavirivae

-, ss, 2 segs, ambisense

Class VI

Retro-viri. Positive polarity. Reverse transcriptase converts RNA to ddDNA --> mRNA --> viral proteins --> mRNA --> progeny virus (contains viral proteins, reverse transcriptase and mRNA).

IF U PURIFY HIV RNA AND EJECT IT INTO A HOST CELL? NO, IT IS REQUIRED TO MAKE DNA AND GO INTO THE CELL NUCLEUS.

Class VII

Virus DNA partially ds circular DNA. Becomes supercoiled DNA upon entry into cell. Makes pregenomic mRNA and mRNA. Pregenomic mRNA makes progeny virus. Normal mRNA codes viral proteins that assist in making the pregenomic mRNA and put it into the capsid. Hepatitis B. reverse transcriptase activity makes progeny DNA.

Retroviridae

Class VI, ss RNA, diploid

Hepadnaviridae

Class VII

DNA virus evolution

Low rate of mutation. DNA polymerase has proof reading

RNA virus evolution

High rate of mutation, highest variablility, instability of RNA polymerase and lack of proof reading, reassortment of segmented RNA viruses. Antigenic shift and drift

Antigenic shift

A sudden change in antigenic type. RNA-reassortment. RNA polymerase may shift segments, so order of RNA is different. Known to occur in influenza Type A. change occurs in one generation.

Antigenic drift

Gradual accumulation of mutations. Usually a one point mutation. Known to occur in influenza viruses. Over many generations, virus is of a different type.

Attenuation

A mutant virus w/o virulence. Danger of back mutation. All live virus vaccines are based on attenuated viruses. ***Stimulated IgM, IgM and IgA***. Limited need for boosters. danger of reversion to “wild type”. Less stable (labile), risky in compromised host, contraindicated in pregnancy. Long term immunity, local immunity (IgA). Cost

Conditional lethal mutants

Select for viruses that dies under certain condition

Phenotypic mixing

Transcapidation, mosaic envelopes. Same genotype of virus, but phenotype is changed.

Polyploidy

Takes more than one copy of a given segment is put into a capsule. HIV requires polyploidy. 2 positive strands must be put into the capsule

Mosaic envelopes

Complementation

Both viruses are put into capsule

Defective interfering genomes

A defective virus requires a homologous helper virus in order to replicate. The defective virus then suppresses the original virus. Coxaki, parovirus. Adenovirus needs to be there for some parovirus to replicate. Class IVa can be problem with RNA polymerase. Can contain multiple origins of replication. May attenuate virulence, cause persistent infections, cause chronic disease. May be used in vaccines

fomites

Vectors

Carriers that inocculate people with viri. Mosquitoes, arthropds, rats. Most hemorrhagic fevers transmitted by vectors (mainly rats). Control of vectors --> control of disease

Public education/awareness

Useless.

Immunological therapy

Usually high effacacy, narrow spectrum, relatively long duration

Chemotherapy

Moderate efficacy, narrow spectrum, very short duration

Interferon therapy

Moderate to high efficacy, broad spectrum, short duration

Inactivated/killed vaccines

May not get complete inactivation, may not confer complete immunity. Works mainly against peplomers. Safe, stable, can be used in compromised hosts. DO NOT PRODUCE IgA. Produces IgM, IgG. Needs boosters. Limited epitope recognition. No local response.

DNA genetic vaccines

Non-replicative in vivo. Easy to prepare. Low level and long term expression of antigens. Ability to modify vectors. Inherent adjuvant activity. foreign DNA may integrate into host DNA disruptine normal genes, causing malignant transformation. Immunologic tolerance may be lost --> Autoimmune disease may be triggered.

Passive immunization

Immune globulin prepared from donors recently recovered from the disease. Used in the immunocompromised or with another vaccine. Used for rabies and tetanus.

Antiviral chemotherapy

Should be specific, nontoxic and selective. Protease inhibitors. Glycosidase inhibitors. Bacteriostatic. Reverse transcriptase is unique to viri, so a good target.

Combination therapy

Synegisic effects. May decrease development of mutants. Acts at multiple points along line of viral replication.

Herpes virus

Shows resistance to chemotherapy

Interferon

Small glycoproteins. Can be released in response to viruses (dsRNA), bacteria, cytokines, mitogens, tumor promoters. Non-specific defence mechanism. Non-toxic, short acting

Interferon Type I

Human type I specific to humans. General acting against viri. IFN alpha: leucocytes; IFN beta: fibroblast; IFN omega: trophoblast

Interferon Type II

Viral specific. IFN gamma: effector T-cells.

2,5-oligoA system

RNase L

IFN gamma

Used against hepatitis C. triggers inflammation

Nucleoside analogues

Defective nucleoside inserted into viral genome preventing the spread of the disease

IFN alpha

Activates natural killer cells

MacConkey agar

Enterobacteriaceae. Differential agar.

Eosin-methylene blue (EMB)

E. coli and Enterobacter aerogenes. Differential agar

Salmonella-Shigella agar

Selective media

Manitol salt agar

Selective media

Transformed cell

Integration of DNA into the host cell. Permissive cell produces virus, non-permissive cells get transformed in DNA viri. RNA viruses can transform permissive cells.

RNA oncogenic virus

Retroviridae. Can transform permissive cells. May not transform permissive cells. Retroviruses carry transduced cellular oncogenes. These oncogenes have NO role in viral replication.

DNA oncogenic virus

Papova, adeno, herpes, hepadna, poxviridae can cause transformation. Can replicate in certain cells of the natural host w/o producing a tumor. Simian virus-40 can live in monkey kidneys w/o any problems, but cause tumors in hamster neonates.

Cell growth patterns

High cell density. Increased rate of growth. Decreased requirement for serum growth factors. Enhanced ability to grow in semisolid medium. Anchorage independent *. Loss of contact inhibition

Cell surface alteration

Some viral proteins will be moved to cell membrane. Surface antigen

Tumorigenicity

Production of tumor when transformed cells are injected into animals. A transformed cell is not necessarily oncogenic. NO in vitro growth characteristic can succedssfully predict tumorigenicity

Highly oncogenic

Carry cellular oncogenes

Weakly oncogenic

Do not carry oncogenes, but modify cell to become oncogenic

Cellular transformation

Introducing new transforming genes into the cell. Induction or alteration of gene expression from a pre-existing cellular gene

Transduction by a retrovirus

Recombination between cellular protooncogene w/ viral genome. Captured cell gene gets mutated and transcribed under strong viral signals

Insertional mutagenesis

Retroviral promoter inserted before a cellular proto-oncogene. Results in enhanced expression of the cellular proto-oncogene. Under influence of viral enhancer sequence

Proto-oncogene

Genes that can become oncogenic under the influence of the proper signals.

Oncogene activation by translocation

Chromosomal translocation of a proto-oncogene from its normal location to near a strong promotor which activates a proto-oncogene

Cis activation

Activation gene is next to gene that is activated. Viral gene is next to oncogene

Trans activation

The activator is not near the gene that is activated

Gene amplification

An increase in number of copies of a certain gene will result in increassed amount of gene product

Ocnogne activation by Mutations

Alteration in proto-oncogene due to mutations or deletions will alter the product

HTLV-1

RNA tumor virus. Human T-cell lymphotropic virus causes cutaneous T-cell leukemia. Expresses large quantities of IL-2 membrane receptors. Is expressed at very low levels. Detected by presence of viral DNA and proteins in malignant cells. Transmission unknown

Tax genes

Carried by transregulating retrovirus. Neceassary for viral replication and may be oncogenic. Proviral sequences found in the DNA of the T-cell and not in the normal cells. In endemic areas (S. Japan, Caribbean and SE USA), upto 10% of the people carry antibodies to HTLV-1 v. 1% in the rest of the world.

Rb and P53

Can form complexes w/ viral gene products that cause transformation. Except for parvoviridae, all DNA containing viruses can cause transformation

Polyomaviruses

Along w/ SV40, the best characterized DNA containing tumor virus. Code for large T, middle T and small t antigens. Large T complexes w/ P53 and Rb genes. Middle t antigen is membrane bound and complexes w/ c-src protein and activates tyrosine kinase

SV40

Codes for Large “T” and small “t” antigens. T-Ag is found tightly complexed w/ cellular tumor suppressor gene product P53 and Rb. Small portion of t-antigen is bound to the cell membrane

BK virus

Not known to cause human disease

JC virus

Virus is regularly isolated from PML patients. Not associated w/ human disease. Found in tumors

PML

Progrssive multifocal luco

Papillomavirus

Majority of vulvar, carvical, and penile cancers. Carry HPV-DNA (HPV-16 and HPV-18) and some other cases exhibit DNA from HPV-11, 31, 33 and 35. tobacco smoke and coinfection w/ herpesvirus have been involved in the progression of HPV lesions to carcinomas

Adenovirus

Rodent cells and induce specific early antigenic proteins localized in the nucleus and the cytoplasm of the transformed cells

E1A

Early protein complexes iw/ the Rb protein

E1B

Protein binds to the cellular protein P53

HHV-1,2 and 5

Can transform hamster cells w/ low frequency.

HHV 2

Associated w/ carcinoma of cervix. No herpesvirus-induced transforming genes has yet been found

???HHV-4

Infects B-lymphocytes and in immuno-deficient individuals, the infection may progress to B-cell lymphomas. Linked to Burkitt's lymphoma.

Poxviruses

Molluscum contagiosum virus produces small benign growth in humans. Very little is known about the proliferative disease. A poxvirus-coded growth factor that is related to epidermal growth factor and to transforming growth factor may be involved.

Nasal terbinate

Foster removal of large particles

Nose-alveoli temperature dif

4 degrees centigrade. Most viruses stay in the upper cooler area

Ciliated epithelia

Clear material upwards out of respiratory tract

Goblet cells

Secretes mucins. IgA will also be secreted

Clara cells

Secrete a protease which activate the viral fusion factor required for entry of some virus particles

Macrophages

Found in alveoli. Clear alveoli of debris because they do not have mucous or ciliated cells. Also found through the rest of the respiratory system

Granular cells

Produce surfactants

Nasal response to virus

Epithelium becomes swollen and edematous producing congestion and fluid accumulation.

Gingival, buccal cavity and nasopharynx

Sights of viral localization

IgG and IgA

Predominant antibodies in the lower and upper RT. IgA dominates upper tract. IgG dominates lower tract. Both found everywhere.

IL-6

Reverts IgA producing plasma cells to B-cells. Produced in response to influenze

Receptor sites

Ubiquitous throughout the host

Budding

Apical or basal budding decides the course for the spread of the virus through the body. Restricted to surface or spread through the body.

Environmental factors

Temperature, humidity, crowding and size of infecting dose

RSV

Respiratory synctial virus. Infection of young people. Enveloped virus (less stable than naked virus). MOST COMMON LRT in pediatrics. 3 antigenic types. Usually acquired from adults w/ subclinical URT infection w/ RST. Main protection from IgA in upper respiratory tract. In infants under 6 months, the virus rapidly moves to LRT producing profuse inflammation, monocyte infiltration, and interstitial pneumonia w/ syncitium formation. Diagnosis by IF (immunoflourescence) or ELISA. Reinfection occurs and immunity increases. Occurs largely in winter. Ribavirin, given in aerosol in severe cases. Vaccine in development

Direct contact

Method of RSV spread.

Aerosol

Measles virus. Sneezing and coughing

Sneeze

100 to 2000um particles at 100 ft/sec to 2-5ft

Cough

850 ft/sec

Normal flora

Micro-organisms living in the upper RT w/o disease production. Herpes virus

Professional invaders

Those that will attack healthy tissue. Influenzae and rahbda virus??. Adhere to normal mucosa. Interfere with ciliary action. Resist destruction by macrophages. Damage mucosal and submucosal tissue

Secondary invaders

Attack hosts that have impaired defenses. Staph aureus and strep pneumoneiae. Damaged respiratory cells, local impairment of defenses due to chronic respiratory illness, chronic irritants (bronchitis, foreign bodies, tumors), reduced resistance resulting from old age, alcoholism, renal impairment, and reduce immune response

Acute

Replication only in respiratory mucosa (influenza, corona-, rhino, parainfluenza viruses

Persistent

Spread to lymphoid tissue and tonsils (adenovirus)

Systemic

RT infection spreads to other organs (mumps, measles, herpersvirus)

CPE??

Common cold

Rhinoviruses and coronoviruses are the cause of more than 50% of the cases. Coxsakie A-, echo-, adeno-, influenza, parainfluenze respiratory syncycia. Diagnosed by clinical picture. Identification of causative agent for epidemiology is by ELISA.

Picronaviridae

Class IVa. Binds to ICAM-1 and is endocytosed. One particle can establish infection. Upper RT infection. Human to human transmission. Incumbation 2-3 days. Symptoms last 3-7 days. Asymptomatic carriers. No known reservoirs

Corona virus

25-30nm. Upper RT. Class IVb. Enveloped virus w/ helical nucleocapsid. Envelope is made of ER and golgi. Secreted by cellular secretory mechanism and by cell destruction. Isolated to humans, no cross infections w/ animals. Patchy destruction of ciliated epithelium. Restricted to URT. Incubation is longer than rhinovirus. Low-grade fever, rhinorrhea, cough, sneezing and runny eyes. World wide infection of all ages. 87-100% of healthy individuals have antibodies to the identified serotypes. Reinfection of the same serotype possible because neutralizing antibodies are short lived. Peak incidence in winter and spring.

Pharyngitis/Tonsilitis

Usually caused by either damage to the respiratory mucosa or by inflammatory response in the lymphoid tissue.

Adenoviruses

Class I, w/ penton fibers. Icosahedral, naked virus w/ fibres attached to each penton. Immediate early proteins push cell to S phase. More than 100 serotypes. Neutralizing antibodies against the fibres. Causes broad range of disease.

Endemic adenovirus

Transimission by respiratory and feco-oral route. Symptoms include fever, pharygitis, tonsilitis and cough. Zoryza, vomiting, diarrhea, meningeal signs and pulmonary infiltrate in 50% of patients. Pediatric respiratory infection 2-7% by age 2 and 50-70% have neutralizeing antibodies against serotypes 1 and 2.

Sporadic adenovirus infection

Pharyngo-conjunctival fever (PCF). In swimming pools w/o adequate chlorination. Swimming pool only leads to conjunctivitis w/o pharyngitis. Caused by serotypes 3, 7. fever lasts for 3 to 4 days after 5 to 7 days incubation. Headache, fever (103 degrees), malaise, anorexia, sore throat.

Epidemic adenovirus infection

Serotypes 8 and 19. ocular morbidity, chronic w/ permanent visual impairment. Incubation 3 to 21 days, lasts for ~2 weeks. Unilateral or bilateral conjunctival infections.

ARD

Adenovirus. Upto 80% of military recruits. Civilians have limited occurance. Transmitted by respiratory droplets. Fever, malaise, nasal congestion, sore throat, hoarseness, headache and cough

Adenovirus in immunocompromised

Mostly in lungs but can spread anywhere.

CF most useful

4 fold rise in antibody titer. Isolation of wirus from throat of feces.

Adenovirus vaccines

**Serotypes 3, 4, 7 and 21. oral live attenuated virus. Spread to close contracts is not significant

Adenovirus epidemiology

World wide, temperate zones, unclean environments (feco-oral transmission).

Parainfluenza virus

4 types of antigens. Cross react and elicit heterotypic antibodies. Type 1 and 2 in late summer and fall. Type 3 throughout the year. IgA is short lived. No real treatment or vaccines.

Otitis media

Infection of middle ear, the sinuses and the epiglotis occur by direct extension of infectious agents from the nasopharynx. Mostly caused by a variety of viruses. Can cause dissyness

Laryngitis

Viral infections are the main source. Parainfluenza and RSV

Traneitis

Viral infections are the main source. Parainfluenza and RSV

Acute bronchitis and bronchiolitis

Both bacteria and viruses cause the condition. Damage cilia caused by viruses in the URT allow bacteria to establish. Loss of cellular integrity may allow extension of infection into bronchioles and alveolar spaces

Chronic bronchitis

Caused by a combination of normal flora (secondary invaders) and irritants such as ciggarette smoke and air pollution

Bronchiolitis

Largely in children. Occlusion of narrow bronchioles. 2/3 or more of the cases are due to RSV. Emerging milder disease – metapneumovirus

Paramyxovirus of turkeys

A pneumovirus. Causes bronchiolitis in infants upto 2 years of age. Inflammation of bronchioles but milder disease than RSV. Complications due to CF and chronic lung disease. 38 cases w/ 3 deaths in Brisbane. Baby does not want to eat. IF or RT-PCR

Influenza virus

2 different peplomers w/ different activities. Binds to sialic acid containing glycoproteins. Transcriptional complex is transported to the cell nucleus. Viral polymerase cleaves 10-13 nucleotides from the newly synthesized host mRNA from the 5' end and uses this capped RNA as a primer for the synthesis of viral mRNA (cap stealing). Another mRNA is synthesized that serves as a template for the negative strand RNA.

Influenza internal antigens

Nucleoproteins can be used to classify into groups A, B, and C

Influenza external antigens

Inlfluenza A can be divided into subgroups based off of surface antigens. Hemagglutinin and Neuraminidase

Hemagglutinating antigen

15 different antigenic types have been identified in birds and animals for influenza A. In contrast, influenza B is found only in humans. HAs are responsible for attachment of viirons to cell. Fusion activity, and stimulation of neutralizing antibodies.

Neuraminidase

Enzymatic activity that allows for virus to burst out easier. 9 antigenically distinct surface glycoproteins have been identified for influenza A. All influenza B have cross reaqcting NA

Antigenic drift

Only in influenza A. STILL CROSS REACT

Antigenic shift

Influenza A. mutations or gene reassortment. Animal reservoirs can be a reservoir for new pandemics

Influenza pathogenesis

NO production is inhibited --> No clearance of bacteria. NA destroys mucus allowing HA mediated endocytosis. Kill mucus cells and causes them to desquamate

Influenza manifestations

Influenza complications

Primary viral pneumonia, secondary bacteria infections, Reye syndrome, Guillain-Barr syndrome

Reye's syndrome

??. Caues brains to swell. Aspirin can trigger syndrome in kids w/ influenza virus or chicken pox.

Guillain-Barre syndrome

Can occur from the vaccine for influenza virus as well as from the virus itself.

Influenza diagnosis

IF, ELISA, and HAI (four fold rise in the antibody titer)

Epidemic threshold

Concept provided a method of estimating the number of influenza virus infections in the community without virus isolation and laboratory identification

Vaccination for influenza virus

Not very effective. Strain specific. May not correctly predict the strain that will emerge. Types of vaccines: inactivates whole virus, split virus, attenuated virus. Loss of concentration, insomnia, nervousness, anxiety, confusion, drowsiness.

Amantidine

Block the ion channels formed by influenza A. does not work against influenza B. Resistant mutants arise frequently.

Rimantidine

Block the ion channels formed by influenza A. does not work against influenza B. Resistant mutants arise frequently.

SARS

Severe acute respiratory syndrome. Cause unknown.

Avian influenza

22 cases in humans. 75 out of 1100 had eye problems due to avian influenza virus.

Rhinovirus

Picornaviridae

class IVa

Human->human

year round infection

110 serotypes

Binds ICAM. Endocytosed. Goes to URT and rarely LRT.

Nonspecific PH. No vaccine

coronavirus

Class IVb

Human only. Peak incidence in winter, spring.

Unknown serotypes

URT only. Low grade fever, rhinorrhea, cough, sneezing, runny nose.

Alpha-interferon

vaccination not practical

ELISA, IF

Adenovirus

Adenovirus

Class I

> 100 serotypes

2 antigenic determinants

fibre has a specific HA determinant

respiratory + fecal transmission

worldwide, temperate zones.

ARD transmitted by resp droplets

Pharynx and tonsils. Fever, cough, vomiting, coryza, diarrhea, meningeal signs and pulmonary infiltrates.

Antibodies against Serotypes 1, and 2 by age 2

pharyngo-conjuntival fever (PCF) (serotypes 3, 7)

Topical alpha-interferon

vaccines for serotypes 3,4,7,21

Parainfluenza

Paramyxovirus

class V

Pharynx and tonsils

RSV

Paramyxovirus

Class V

Pharynx and tonsils

URT defenses

Lysozyme, lactoferrin, sIgA. Mucociliary escalator

LRT defenses

IgA and IgG, complement components, macrophages, Mucociliary escalator (not in alveoli)

Uncommon infections

C. diphteriae, K. pnemoniae, Pseudomonas spp., E. coli, C. albicans (is present in URT)

Predisposing factors

Damage to mucociliary cleaning mechanisms, irritants, intubation or other by-passing of normal defenses, general anaesthesia, inherited factors (cystic fibrosis), age

Professional pathogens

Capable of infecting healthy RT, adhere to normal mucosa, interfere w/ action of cilia, evade removal, damage local tissue

Secondary pathogens

Require impaired host defenses. Initial damage to RT, Chronic bronchitis, depressed immune response, or depressed resistance --> impared defenses.

URT infections

Conjunctivits, otitis media, sinusitis, Streptococcal pharyngitis, epiglottitis, diphtheria, bronchitis

LRT infections

Pneumonia, whooping cough, bronchitis?? pg 25-4 and 25-1 conflict

Eye defenses

Washing effect of tears (contain lysozyme)

Eye infection transmission

Poor hygiene, fomites, use of poor contact lens hygiene

Eye infection symptoms

Sore itchy eyes, purulent discharge, reddened conjunctiva

Eye infection pathogens

H. influenzae, S. pneumoniae, S. aureus

Eye infection treatment

Antibiotic drops and ointments

Otitis media

Mostly children 6-36 months. Edema and blockage of eustachian tube w/ impaired drainage of middle war fluid. Caused by S. pneumoniae, H. influenzae, S. aureus, beta-hemolytic streptococci. H. influenzae is MOST COMMON

Otitis media symptoms

Fever, headache, reddened bulging eardrums, if untreated -> drum perforation and purulent discharge.

Chronic otitis media

Fluid persists for weeks to months “glue ear”

Acute otitis media

form Common as a complication of thinovirus infection because normal flora become trapped in middle ear

Otitis media diagnosis

Gram stain & morphology. Catalase production – streps from staphs. Chocolate agar w/ C and V factors (H. influenzae)

Acute sinusitis

Range of secondary bacterial invaders same as for other URTIs. Blockage of eustachian tubes or openings of sinuses --> no mucociliary clearance --> local accumulation of inflammatory bacteria --> more swelling. H. influenzae is the MAJOR CAUSE in CHILDREN. Pneumococci also can cause it

Sinusitis diagnosis

Clinical features, microscopy and culture of aspirated pus (sinus puncture not usually carried out).

Sinusitis treatment

Elevation of head and decongestants

Acute epiglottitis

Most serious. Can be rapidly fatal. Destruction of airways due to swelling of epiglottis and surrounding structures. Most common in young children. Characterized by acute inflammation, edema and neutrophil infiltration. Initial low grade fever --> elevated temperature (39.5), sudden onset of breathing difficulties. H. influenzae is the most common cause. Severe invasive disease particularly associated w/ capsular ype B. Others of the 6 capsules can be present as local flora

Haemophilus influenzae in epiglotittis

Common component of URT microflora. G- coccobacillus. Facultative anaerobe. Polysaccharide capsue, IgA protease, naturally competent (transformation), produces catalase. Vaccine available. Diagnosis by culture on chocolate agar. Detection of capsular antigen (latex agglutination), radioimmunoassay. Can be prevented via vaccine, polyribose-ribitol phosphate coupled to protein carrier, T-cell response, can induce T-cell response in children as young as 2 months

Pharyngitis

Pharyngitis is the most common type of S. pyogenes infection. Can also be caused by C. diphtheriae, H. influenzae, N. gonorrhea. Severe purulent inflammation of oropharynx and tonsils. White exudate; enlarged erythematous tonsils, swollen anterior cervical nodes. Throat discomfort, malaise, fever, and headache. Complications include scarlet fever, rheumatic fever and acute glomerulonephritis, and invasive group A streptococcal diseasse

Scarlet fever

Complication of pharyngitis. Punctuate erythematous rash (sunburn-like) on neck, trunk and extermities. Spread of erythrogenic toxin

Group A Streptococci

S. pyogenes. Lancefield classification according to cell wall carbohydrate. Virulence factors streptokinase, hyaluranidase, hemolysins. Pharyngitis most common infection. Diagnosis on blood agar. Characteristic small opalescent colonies. Beta-hemolytic, bacitracin sensitive, optochin resistant. Antigen detection kits available. Rapid eradication of organism can prevent development of rheumatic fever.

Diphteria

Corynebacterium diphteriae. Vaccination makes this rare. Early diagnosis is critical. Block ADP-ribosylation of EF-2. 1B:1A toxin. Symptoms: swollen “bull” neck, temporary facial and neck paralysis, Greyish pseudomembrane, enlarged cervical lymph nodes. Heart, muscle, kidney, liver and other organ irregularities. Only toxin producing strains are virulent. Foreigners and unvaccinated people susceptible. Presence of a pseudomembrane.

Tinsdale agar

Contains potassium tellurite which inhibits growth of RT flora other than diphteria

Precipitate bands

Elek immunodiffusion test. Sterile filter paper impregnated w/ diptheria antitoxin is imbedded in agar. Isolates of C. diphteria streaked across plate. If toxin present, toxin diffuses away from bacteria and reacts w/ antitoxin --> lines of precipitin

Pertussis

Whooping cough. Caused by Bordetella pertussis. Exclusively human. Highly infectious. Adults provide main reservoir. Highly communicable amongst susceptible infants. Life threatening in infants w/ cardiac or pulmonary disease. Complications: CNS anoxia, exhaustion, secondary pneumonia. Incubation period of 1 to 3 weeks

Neurologic sequelae

Can be caused by pertussis

B. pertussis

Gram negative rod. Inhaled in respiratory droplets coughed by infected individuals. Bind to cilia of epithelial cells. Mediated by Fha (filamentous haemagglutinin). Number of virulence factors: pertussis toxin (1A:5B). Tracheal cytotoxin (inhibits ciliated epithelial cells). Diagnosed w/ FA test

Bronchitis

Inflammation of the tracheobronchial tree. Increase in mucus-producing goblet cells. May see impairment of mucociliary mechanisms. Can be of bacterial or viral origin. Acute and chronic forms. Acute: cough is most prominent symptom. Chronic: cough and excessive mucous.

Chlamydia pneumoniae

Small, obligate intracellular parasite. Community acquired respiratory tract infections. 50% of adults in US have antibodies to this organism. Infections of both upper and lower RT. Rarely causes invasive disseminated infections. Serologic tests and culturing usually not available. Use giemsa stain, immunofluorescence, FA stain, ELISA and DNA hybridization.

Mycoplasma pneumoniae

Increased incidence in late fall and winter. Virulence factor: P1 cytoadhesion. Culture on supplemented agar: small, “mulberry” shaped colonies (corrected from notes). Diagnosis via culture requires 8-15 days. Serologic test more frequently used. Complement fixation. 4 fold rise in tites. False positives can result from infectious mononucleosis, rubella, influenza, adenovirus, listeria infections

Onset

Prodormal period 1-7 days

Rapid: 4-12 hours

Seasonal occurance

Late autumn and early winter

None

Typical age

3 months to 3 years

1 to 6 years

Clinical manifestations

Barking, seal like cough, coryza, low-grade fever, insipiratory and expiratory stridor

Dysphagia, drooling, muffled voice, high fever, inspiratory stridor

Pharyngitis

Penicillin G

Resistance not yet observed in S. pyogenes

Epiglottitis

Ampicillin

Rifampcin for close contacts. prevention = Hib vaccine

Diphteria

Erythromycin, penicillin G

Antitoxin. Vaccine = DPT vaccine

Otitis media

Amoxycillin

Sinusitis

Ampicillin, amoxycillin

Pertussis

erythromycin

C. pneumoniae (bronchitis)

Doxycycline or azithromycin

M. pneumoniae (bronchitis)

Doxycycline or erythromycin

Protracted paroxysmal coughing (worse at night)

100

100

SOB during coughing

86***

0

Tingling sensation in throat

86***

0

Sleep disturbed by cough

57

100***

Whoop soung with cough

7

40

Cyanosis with cough

0

40

Pneumonia

Infection of the lung paranchyma. Most common cause of infection related death. Overwhelming inflammatory response (which gives pathology). Influx of fluid into the lung alveoli. Interferes w/ gas exchange.

Signs/Symptoms

Fever, general feeling of sickness, chest pain – frequently pleuritic, cough (productive/non-productive), SOB, rapid respiration, poor colour, cyanosis, rales, shadowy infiltrate on CXR.

CXR

Chest X-ray

Systemic effects

Fever, shock, wasting

Local effects

Interference of lung function

Pneumococcal pneumonia

Can heal w/ no scar formation.

G- rods

Permanent lung tisse destruction

Anaerobic bacteria

Permanent lung tisse destruction

Anatomical involvement

Lobar v. bronchopneumonia

Lobar pneumonia

Most commonly pneumococci than with Staphylococci

Epidemiological markers

Hospital/nursing home, chronic lung disease, elevated neutrophil count = bacterial infection, age, onset and course, anatomical involvement (lobar or bronchiole)

Streptococcus pneumoniae

CAP. Follows URTI. Occasional cause of pneumonia. Normal flora in 5-40% of healthy individuals. Causes lobar pneumonia. Spreads between the alveoli until contained by anatomical barriers. Highest incidence in children < 5 years of age and adults > 40. high incidence in African Americans and native americans. Penicillin resistant (altered target).

Mycoplasma pneumoniae

CAP, young adults, summer & fall. Gradual onset, nonspecific symptoms. Flu like symptoms progessing to Dry/scantily productive cough. Earache, CXR: patchy, diffuse bronchopneumonia (involves > 1 lobe). No gram stain (no cell wall). Nucleic acid hybridization test. Culture may require 7-10 days. **ELISA is prefered choice. Complement fixation also possible. Does not have “Fried egg” colonies, but mulberry shaped colonies. Probably won't be sick enough to require hospitalization.

Haemophilus influenzae

G- bacilli (is actually pleiomorphic). CAP, Follows URTI. Part of normal flora. Also causes epiglotittis, otitis media, and meningitis. DOES NOT CAUSE INFLUENZA. Type b (capsule) most virulent. Median age of infection is 1 year. False-negatives and false-positives common. Component of normal flora. Diagnosis via chocolate agar w/ X and V factors. IF detection of capsular antigens.

Chlamydia pneumoniae

CAP. Lobar pneumonia. Small gram -. obligate intracellular parasite. General symptoms: Headache, fever, cough (non-productive), mialgia. Chronic infections associated w/ cystic fibrosis, lung cancer, and asthma. Can not gram stain. Giemsa stain for intracytoplasmic inclusions. **Complement Fixation (CF) test is most widely used. ELIA and Fluorescent antibodies also available.

Staphylococcus aureus

CAP & NAP. Associated w/ influenza. Part of normal flora. Necrotizing pneumonia

Klebsiella pneumoniae

CAP & NAP. Chronic alcoholics, diabetes, COPD. Necrotizing pneumonia. Carried by 5% of healthy individuals. Has a large capsule. See a lot of damage to lung tisse. Most damage due to endotoxin. Positive to V-P reaction and citrate reaction. Culture is pink, very viscous, muccoid colonies.

Moraxella catarrhalis

CAP & NAP. Pre-existing lung disease

Escherichia coli

NAP

Legionella pneumophila

CAP & NAP. Exposure to contaminated source. Multi-system symptoms. Develops in 1-5% of people exposed to common source. Early symptoms non-specific: fever, myalgia, malaise, anorexia. System ic effects: Watery diarrhea (25-50% of cases), nausea, vomiting. Severity and range of associated symptoms varies widely. Much of local damage due to host inflammatory response. Virulence factors:intracellular growth, possibly endotoxin , and possibly extracellular protease. Can be picked up from water fountains or from tap water, showers, air conditioners. Predisposing factors: men, immunocompromised, age, heavy alcohol consumption, debilitation, exposure to contaminated source.

Pathogenesis of pneumococcal pneumonia

S. pneumoniae infection --> outpouring of fibrinous edema fluid into alveoli, early (red) consolidation (red cells and leukocytes) (good growth medium for bacteria) --> late (grey) consolidation (consolidation of portions of lung (alveolar walls remain intact) macrophages and cell debris) --> resolution.

S. pneumoniae virulence factors

Capsular polysaccharide (85 serotypes... now 90). IgA protease, or no toxin

Pneumococcal pneumonia diagnosis

Initially dry cough --> purulent, blood-streaked or rusty sputum. Diagnosis by nasopharyngeal swab: culture on blood agar: G+; pairs. Alpha-hemolytic, growth inhibited by optochin, Quellung test, coagulase negative

Vaccination against pneumococcal pneumonia

“polyvalent” capsular polysaccharide vaccine. Immunizes against 23 (85-90% of infections) of the most common serotypes. Heptavalent conjugate vaccine: 7 pneumococcal antigens conjugated to CRM197.

CRM197

Mutant non-toxic diphteria toxin. Can be bound to pneumococcal antigens for vaccination

Chlamydia psittaci

Causes pneumonia following contact w/ sick birds. Can get pneumonia from this organism. Bird handlers.

Differentiating L. pneumophila

Gram stain to demonstrate neutrophils. Gimenez stain (intracellular). Culture from RT. Buffered charcoal yeast extract agar (BYCE). Supplement w/ L-cysteine; low sodium. Detection: all approaches have limited sensitivity. DFA test. Radioimmunoassay (antigen in urine)

Necrotizing pneumonia

>1 area of lung parenchyma replaced by cavities filled with debris. Large % of cases involve anaerobic bacteria and can be polymicrobial (grow in the center of biofilm). Aspiration of oropharyngeal contents into lungs (occurs w/ seizure, drug overdose, and excessive alcohol intake). Breathe has putrid smell. Fever of several weeks duration. Cough.

Pseudomonas aeruginosa

Gram – rod. Common oppurtunistic pathogen widely distributed. Culture in simple media: produces pyocyanin (yellow-green pigment). Oxidase positive.

S. pneumoniae

Penicillin

H. influenzae

TMP-SMX

M. pneumoniae

Erythromycin or tetracycline

C. pneumoniae

Tetracycline

L. pneumophila

Macrolide or fluoroquine

K. pneumoniae

Cephalosporin

P. aeruginosa

Aminoglycoside + antipseudomonal penicillin. Resistant to many antibiotics.

Onset

Sudden

Insidious

General appearance

Toxic

Malaise, fatigue

Fever

Yes, > 39 degrees

Low < 39 degrees

Chills

Common

Rare

Cough

Productive

Rare

Sputum

Purulent

Scant/none

Gram stain

Bactera + WBC

Mixed oral flora

WBC

Elevated, left shift

Normal +/- lymphocytes

CXR

Lobar consolidation

Brochiopneumonia (patchy)

Organism invovled

S. peumoniae, H. influenzae, S. aureus

M. pneumoniae, C. pneumoniae, L. pneumoniae

Ajellomycces dermatidis

Formerly Blastomyces dermatidis. North american blastomycosis. True dimorphic fungi. Largely sourtheastern United States. Spread by droplets. Usually comes from breathing spores from ground living animals. Primary walking pneumonia (infectious). Secondary: Cutaneous granulomatous lesions (often on the face and extremities). Slow growing, lesions take years to get as bad as the pictures. Cross reactivity w/ histoplasmosis. Delayed hypersensitivity skin test. Immunodiffusion test. Identify organism in tissue. Treatment: systemic (topical is useless); use amphotericin B for pulmonary diseases or immunosuppressed patients. Normally FLUCANOZOLE

Paracoccidioides dermatidis

Formerly Blastomyces brasilensis. South american blastomycosis. Loosely located in central and South America. Rare. Primary walking pneumonia. Secondary: disfiguring granulomatous lesions in oral cavity. Often discovered by dentists and oral surgeons.

Ajellomyces capsulatum

Formerly Histoplasma capsulatum. Histoplasmosis. Common. Found in the missouri and mississippi valleys. Occasional cases found in Greater Antilles (Cuba, peurto rico, Hispaniola). Walking pneumonia. Usually disappears in 3-6 weeks. Occasionally develop mediastinal fibrosis as a result of over-active immune response. In immunosuppressed, disease may metstasize to anywhere. Caseated lung nodule. Similar to tuberculosis, often indistinguishable. Yeasts observed in WBC. Tuberculate macroconidia grow in Sabouraud's . amphitericin B for severe cases. Life-long suppressive therapy.

Coccidioidiomycosis

Coccidiodes immitis. Desert fever. Found in high desert dust. Walking pneumonia. 1-2 week course. If it gets to secondary state usually goes to meningitis. See spherules on slide. Serodiagnosis: delayed hypersensitive skin test. Laboratory acquired infections. Specific exoantigen test.

Cryptococcosis

Cryptococcus neoformans. Birds are not vectors, but there droppings make fertile growth areas. Walking pneumonia. Secondary usually meningitis. Most common fungal infection of AIDS patients. Backwards serodiagnosis. India ink negative stain (stains everything but the yeast). Culture is definitive diagnosis. Treatment: Combination of amphotericin B and 5-flurocytosine. Urease positive, encapsulated and inhibited by cycloheximide

Pneumocystosis

Formally Pneumocystis carnii. Reproduces like a sporozoan parasite. New name is Pneumocystis jiroveci. PCP: pneumocystis pneumonia. No ergosterol in cell wall. Difficult to grow in culture.

Aspergillus sp.

Aspergillus fumigatus. Opportunistic infection. Different organ systems may be infected. Usually immunocompromised URT and LRT infections, sometimes brain or eye. Fungus balls. Gummatus lesion.

Mucor sp.

Rhizopus sp.

Pneumonic aspergillosis

Requires predisposing factors: neutropenia. Large amounts of amphotericin B. Usually lethal (immunocompromised patients). Worldwide distribution. Progressive diffuse pneumonitis. Direct FA stain of organism in sputum for diagnosis. Treat w/ trimethoprim-sulfamethoxazole. Prognosis is poor.

Mycobacterium

Fungus-like bacteria. Aerobic, gram+ (if stained), large rods. No true branching. Strongly acid fast. Not penicllin usceptible. Resists drying but sensitive to heat. Do not form spores. Grow slowly (12-24 hour generation time) (6 weeks to culture and claim negative). Like egg media (Lowenstein-Jensen agar) (oleic acid -albumin broth).

M. smegmatis

Will grow anywhere (faucets, walls....)

M. leprae

Will not grow in artificial culture or tissue culture at all

Muramic acid

Component of mycobacterium cell wall. Polymer consists of N-glycolylmuramic acid (instead of N-acetylmuramic acid) alternating w/ N-acetylglucosamine.

Mycolic acid

Component of cell wall. Lipid. ~84 carbons

Wax D

15-20 molecules of mycolic acid esterified to a large polysaccharide. Allows resistance to drying. Heat is not impeded. Slow growth because nutrients are impeded as well. Allows for acid fast properties. Wax holds acid dye in place.

Arabinogalactin

In a thin layer to outer surface of the muramimc acid layer

Trehalose dimicolate

Complex lipid on outer surface. Responsible for the aggregation of cells in parallel bundles or “Cords”

Cord factor

Trehalose dimicolate. Only found in virulent strains. Inhibits migration of neutrophils. Binds to mitochondrial membrane, damages respiration and oxidative phosphorylation, induces synthesis of cachectin --> cachexia

Cachectin

Tumor necrosis factor

Cachexia

Wait loss resulting from the presence of cachectin

M. tuberculosis

Causes TB.

M. bovis

Causes TB in cattle and humans

A. avium

TB in birds and humans (more highly drug resistant)

M. marinum

TB in fish. Leads to cutaneous lesions in humans

M. ulcerans

Leads to skin ulcers in humans

M. kansasii

TB-like disease in humans. Same pathologenesis and symptoms

M. inracellulare

TB-like disease in humans. Same pathologenesis and symptoms

M. scrofulaceum

Lymph node infection in humans

M. fortuitum

Various human diseases

M. leprae

Leprosy

Scotochromagens

Runyan group II. Scrofulaceum, szulgai

Photochromagens

Need light. Runyan group I. Kansani, marinum, simii

Nonchromogens

Don't need light. Runyan group III. Avium, intracellulare, ulcerans

Fortuitum

Rapid growers. Runyan group IV. Fortuitum

Reservoirs

Men (and women). M. bovix and M. avium have animal reservoirs

Spread

Density dependent. 1/3 to ¼ of world population carries the latent type of infection. Minimum infectious dose is relatively small. High level of immunity. People w/o long exposure to TB have higher incidence and death rates

Pathogenesis

Coughed TB --> inhaled by close contacts (usually aborted but if not)--> bacilli are ingested by macrophages(usually killed, but if not) --> latent infection (bacteria lives in granuloma --> 10% active disease (weight loss, fever, coughing) infective

Primary tuberculosis

Inhaled bacilli reach the bronchi. Bacilli outlive macrophage and are released unharmed. Granuloma forms eventually becoming caseated. Self limiting

Reactivation tuberculosis

The most active clinical disease. Areas of high oxygen tension and low drainage (apex of lungs). Spreads w/ frequent coalescing. Bronchules and small blood vessels are frequently eroded. Can occur in other organs: brain, kidney, bone marrow, meninges. Major symptoms don't occur until disease is fairly well progressed: coughing up blood (haemoptysis), cachexia (wasting away), loss of vitality, death to wasting, respiratory insufficiency

Syncitium

Cells w/ no seperating membranes (giant cells)

Ghon complex

Granuloma (multinucleated giant cells w/ caseating necrosis)+ enlarged regional lymph nodes

Tuberculosis in AIDS

~10% of HIV pop has TB. CNS invasion in up to 10%. CD4 cells important in immune response

Coin lesion

Presumptive diagnosis

Definitive

Ziehl Neelsen staining. Culture from sputum sample

Antimicrobial resistance testing

Must be done on culture since resistance to vairous antibiotics is wide spread

Tuberculin

Cell-free culture. Used in PPD test. Originally developed to develop immunity

Streptomycin

Isoniazid

Rifampin

Pyrazinamide

Ethambutol

BVG

Vaccine. Live attenuated strain derived from M. bovis. Varying reports of effectiveness, ranging from useless to 80%

Bronx box

Determines antibiotic resistance in TB.

Hepatitis A virus (HAV)

Structure: icohahedral, naked, 27nm diameter. Picornaviridae. Enterovirus -72. withstands heating (boiling) and disinfectants. Spreads via oro-fecal route and uncooked shellfish (clams and oysters). (For the exam – only oro-fecal transmission). Incubation period 15-40 days. Abrupt symptoms: fever, nasuea, vomiting and jaundice due to necrosis of liver cells. Recovery complete in 8-12 weeks. Pediatric cases mild and undiagnosed.

Picornaviridae

Class IVa. Makes long single strand of mRNA

Hepatitis B virus (HBV)

Serum hepatitis, long term hepatitis. Hepadnaviridae (class VII). Viral coded DNA polymerase serves as reverse transcriptase. Danes particles in serum and viral surface antigen (most useful indicator). Danes particles, 42nm in diameter, found in patients serum. Incubation is 50-180 days. Blood bourne. Transdusion or contaminated needles. Oral and sexual transmission. Chronic carriers and IVDA are main source of infection. During later half of infection. Body fluids contain virus. Black fly has transmitted hep B (odd route, on an exam WRONG ANSWER). Symptoms: fever, rash, arthtitis) rare cases anicteric. Overall mortality ranges from 1-2%. 5-10% have HBsAG for life. 8-10% have high concentrations of Dane's particles. All carriers have anti-HBcAg and some have anti-HBeAg. Correlation w/ hepatocellular cecinoma

Class VII replication

Pregenomic RNA is in capsid w/ RNA polymerase that makes DNA. Once first DNA strand is made, the RNA is spliced and serves as a primer for the second strand. First strand is incomplete because of polymerase and the second because of the primer.

HBV Surface antigen

HBsAg. Non-soluble antigen. Most useful marker. Several subtypes have been identified. Detected in large quantities in infected serum, pleomorphic in shape under EM.

HBeAg

Indicator of serum infection. Virus can be transmitted. Part of core antigen. Cleavage product of viral core protein.

HBcAg

Observed in infected hepatocytes. Core antigen. Core protein has protein kinase activity. no free HBcAg in serum

Dane's particle

Whole HBV.

HBV oncogenesis

Tumor cells obtained from liver contain HBV-DNA. HBV carries no oncogenes, mechanism of oncogenesis unknown. Maybe insertional or transactivating mechanis.

Anti-core antibody

Surface antigen is the first to appear in large quantities. Anti-core antibody appears next in high quantitiy. Completely obsorbed by virus antigens, so not all antigens can be attacked (very high quantitiy). Eventually all HBsAg will be cleared, so anti-core antibody must also be detected because of this clearing.

Chronic HBV

Balance between surface antigen and antibody because body gives up. Windo period is early in infection. HBsAg falls for only a short period of time. Pg 30-7A. Anti-HBs and HBsAg.

HBV control

Screening of all blood for HBV (and HCV). Vaccines: inactivated (heptavax) and recombinant HBsAg (recombivax).

HBV vaccine

Only Anti-HBs antibodies. NO anti-HBc and NO antigens. Available for high risk individuals.

HBV cleared infection

Anti-HBs and anti-HBc.

Retro v. hepadnavirididae (not imp)

Reverese transcriptase activity. chronic infection of cells w/ destruction. Order of functional genes retro: gag-pol-env. Hepadna: C-P-S. Both can cause some cancers.

Hepatitis C virus (HCV)

Flaviviridae (class IVa) virus. Icosadedral w/ nucleocapsid. Sexual and IVDA transmission. Incubation 40 to 120 days. High liver enzymes used for prediction (ALT). 50% develop chronic liver disease and many develop cirrhosis and hepatocellular carcinoma

Alanine amino transferase

Liver enzyme that rises w/ liver damage

HCV treatment

No vaccine available. Prescreening of blood. PEGylated Inferferon Alpha for treatment.

PEG

Polyethylene glycol. Not very immunogenic. When attached to interferon alpha, it slowly detaches releasing interferon alpha slowing down interferon clearance.

Hepatitis D virus (HDV)

Enveloped agent. 35-40nm in diameter. Negative polarity ss negative circular RNA. Only one protein coded: delta antigen. Requires presence of HBV. Virus replication localized to the hepatocyte nuclei that do not contain HBcAg. Spreads through blood products and IVDA. Vertical transmission possible. Simultaneous infection of HBV and HDV results in mild infections. HDV infection subsequent to HBV infection results in rapid and severe hepatitis.

HDV treatment

Just treat HBV since it is a necessary precursor. Diagnosis by detection of anti-delta IgM and/or IgG.

Hepatitis E virus (HEV)

Caliciviridae. Small icosahedral naked virus. Transmitted to non-human primates through human feces (oro-fecal) and recovered from infected animals. Reservoir: pigs, rats, monkeys (all speculative). No vaccine

Hepatitis F virus (HFV)

Togaviridae. Oro-fecal. Icosahedral. No treatment

Hepatitis G virus (HGV)

ss positive RNA.

Hepatitis TT virus

Circoviridae (w/ negative polarity). Isolated in 1997. sexual, breast feeding transmission. No vaccines available.

HHV 4

Human herpes 4. Epstein bar virus. Causes liver infection

Yellow fever virus

Causes liver infections

Other viral infections (dntk)

Cytomegalovirus, HHV 1, varicella virus, rubella (congenital rubella syndrome)

Coxsackie B virus (dntk)

Heart, muscle (pleurodynia)

Cytomegalovirus (dntk)

Kidney, glands

Mumps (dntk)

Glands

HHV-1 (dntk)

Liver, eye

Eye infections (dntk)

HHV 1, adenovirus, measles and rubella, enterovirus 70, coxsackie A24 virus

Betaherpesvirinae***

Long viral replication cycle (48hrs). Infected cells are swollen (cytomegaly), not lysed. Latency in glands, kidney and liver.

Alphaherpesvirinae

Short cycle.

Gammaherpesvirinae

HHV 5

Cytomegalovirus. Mostly subclincial. Breast milk, saliva, urine, semen, genital secretions. Shed virus for long time. Giant cells w/ cowdry type A inclusion bodies. 50% of babies ofund infected when mothers had primary infection during pregnancy. Latent infection life long. Virus shed in saliva and urine for months to years after primary infection (active form).

Congenital CMV

20% symptomatic. Jaundice, microencephly, hepatospleenomegaly and lethargy. Asymptomatic infants develop viruria within 1 week after birth

Perinatal CMV

Vast majority asymptomatic. Pneumonitis may be seen occasionally during first 3 months

Immunocompromised CMV

Leukemia and lymphoma patients at high risk. CMV retinitis, colitis and pneumonia in AIDS patients.

Adenovirus

Resistent to ether. Icosahedreal. 80nm. VA-RNA early RNA that blocks interferon induction. Diagnosis: nuclear inclusion bodies in infected cells. Isolated from tonsils, nasopharynx and intestinal tract of healthy individuals. About 45% of infections result in disease. Oro-fecal and respiratory tract spread during childhood. ***Common group specific CF antigen associated with the HEXON

CMV diagnosis

Virus isolation from saliva and urine. EM observation of virus in urine. RIA and ELISA

Gancylclovir

CMV

Acyclovir

CMV

Refampin

Adenovirus.

Serology test

****4 fold increase in titer. Paired test.

Hemorrhagic fevers

Four families (Flavi, Arena, Bunya and filoviridae). No vaccines

Tetracycline

Increasingly used to treat all hemorrhagic fever

Diagnosis

Serology and virus isolation or genome amplification by PCR

Flaviviruses

Class IVa. Arbovirus (except HCV). All flaviviruses serologically related cross reacting antibodies. Transmitted by insects. Infect macrophages. Cell damage by cell mediators. Tissue destruction by T-cells. Shock syndrome

Shock syndrome

virus-antibody complex enters monocytes via Fic rec. antibody enhances infection. Increased production of cytokines. Severe illness, hemorrhages, shock

Dengue fever

Flaviviridae. Fever, rash, hemorrhagic shock syndrome. Mosquitoes, reservoir unknown. India, SE Asia, Pacific, South America, and the Caribbean, no vaccine available, vector control. Second infection worse than first. Carribean strain is mild; asia strain is bad.

Arenaviridae

Class V. Small positive sense segment to make enzymes. Host ribosomes trapped in viral particle w/ no known function. Looks like sand. Reservoir in rats. Spreads through rat feces and urine

Lassa fever

Arenavirus. Siera Leone. African bush rat. West Africa. 10/21 doctors and nurses died. Diagnosis by CSF and blood. Fever, diarrhea, hemorrhages, hemoconcentration and collapse. Treatment is give saline. Human-human transmission is unknown. 10-50% mortality

Bolivian hemorrhagic fever

Arenavirus. Machupovirus. Bush mouse. NE bolivia. 15% mortality. Fever, myalgia, hemorrhage, shock and neurologic illness. 15% mortality. DDT given to mosqitoes. Mosqitoes eaten by something that is eaten by cats. Cats die, so rats increase.

Argentinean hemorrhagic fever

Arenavirus. Juninvirus. Fever, myalgia, hemorrhages, collapse. Callomys spp. Of mice. 10% mortality

Venezuelan hemorrhagic fever

Arenavirus. Guanaritovirus. Fever, headache, sore throat, pharyngitis, loss of apetite, nausea, comiting, seizures and nose and gum bleeding. 30-40% mortality. No vaccine; rat control. Cane rats and cotton rats

Bunyaviridae

Class V. reservoir in rats, mice, and ticks. Plasma and RBCs leak through vascular epithelium

Korean hemorrhagic fever

Bunyaviridae. Hantaan virus. SW United States. Hemorrhagic fever w/ renal syndrome. No vaccine. Rodent control. Far east, Scandinavia, E. Europe.

Congo-crimean hemorrhagic fever

Bunyaviridae. Niarovirus. Asia, africa. Rodent reservoir, transmitted by ticks. Current epidemic. No vaccine. Rodent and tick control

Filoviridae

Class V. In areas w/ apes and chimpanzes. So far confined to Africa.

Marburg hemorrhagic fever

Filovirus. Marburgvirus. Identified in Germany after Ugandan Monkeys brought in. 20% mortality. Fever, rash, hemorrhage, probably DIC. No known reservoir

Ebola disease

Filovirus. Ebolavirus. Sudan febrile illness, vascular collapse, internal bleeding, death, Sudan and Zaire, no known reservoir or vector. 1976 first case. 90% mortality. Glycoprotein peplomers cause destruction of endothelium of blood vessels resulting massive hemorrhages. 4 recognized strains: Zaire, Sudan, Reston (nonpathogenic), Cote d'Ivoire.

Staphylococcus aureus

Golden yellow colonies on agar. Resistant to drying/heat. Fomites+. Protein A. Exfoliatin. Beta-lastamase plasmid. Tolerance to some antibiotics. Superantigens (enterotoxins) A-F. Folliculitis, boils, cellulitis, SSS, TSS. Catalase positive. coagulase

Protein A

S. aureus cell wall component. Binds to Fc portion of IgG.

Exfoliatin

S. aureus exfoliative toxin

Folliculitis

S. aureus. Minor infection in and around the hair follicles. Surrounding induration and redness. Localized infection.

Furuncle

(boil). S. aureus. Originates as superficial infection (around foreign body or hair follicle. Organisms protected against host defenses. Multpily and spread locally. Fibrin deposited. Site is walled off. Yellow creamy pus formation.

Carbuncle

S. aureus. Clusetered boils -> multifocal infection -> abscesses. Larger and deeper than boils. Can lead to bacteremia. Both boils and carbuncles may require debridement and antibiotic therapy.

Cellulitis

S. aureus. Acute inflammatory process. Infection of cutaneous fat. Originates from trauma, boils or ulcers. S. aureus > 90% of cases. Occasionals GAS. Trauma, burns, surgery...

anaerobic cellulitis

C. perferingens. Bacterial spread along tissue fascia. No muscle invasion

Toxic shock syndrome

30-40% nasal carriage of S. aureus in general population. Organism may be undetectable. TSS: absorption of S. aureus toxin from initial site of infection and transport via blood. TSST-1. Severe shock (<48hours) w/ renal hepatic damage. Surface areas of skin start pealing. 2 forms: menstrual associated w/ super absorbent tampons. Non-menstruals: associated w/ infected surgical wounds, nasal tampons, puerperal sepsis. Fever > 102 degrees, vomitting, sore throat, myalgia, diffuse macular rash, hypotension, diarrha. Age and sex

TSST-1

Pyogenic superantigen

Diagnosis of TSS

Abrupt fever. Take cultures: S. aureus in grape-like clusters, catalase+, coagulase+

Scalded skin syndrome

S. aureus. SSSS. Most common newborns. Children < 5 years of age. Exofliatin. Splits epidermis by cleaving desmosomes present in stratum granulosum. Erythema around mouth that spreads over the whole body. Peel extremely easily.

Nikolsky's sign

Pealing skin in adults. Sign of exfoliatin

Streptococcus pyogenes

Forms chains on agar. Encapsulated (hyaluronic acid). Present on human skin and mucous membranes. Skin infections = typical. Beta hemolytic group A. virulence factor: M protein. Streptococcal pyrogenic exotoxins: A, B, and C. portal of entry determines clinical presentation. Facultative anaerobe

M protein

Component of pili. > 80 types. Binds fibrinogen -> dense coat – blocks complement deposition. Role in pathogenesis of rheumatic fever.

Hyaluranidase

Spreading factor for S. pyogenes.

Streptokinase

Fibrinolysin. Catalyses conversion of plaminogen to plasmin. Degradation of fibrin. Found in GAS.

Hemolysins

Streptolysin O, streptolysin S (responsible for clear zone on BA plates)

Streptococcal pyrogenic exotoxins

A, B, and C antigenically distinct

Erysipelas

Tender, superficial erythematous and edematous lesions especially on face or lower limbs. Pain and lymphadenopathy. Fiery red and rapidly advancing erythema. Unlike cellulitis, clearly delineated margins. Dermis

Impetigo

Intraepidermal vesicles filled with exudate -> weeping and crusting lesions. Acquired through direct contact. Common in children. Peak incidence 2-5 years. S. pyogenes (classic cause) or S. aureus (bullous impetigo. Currently more clinical import.). May occasionally be followed by acute glomerulonephritis. epidemis

Scarlet fever

Erythrogenic toxin. Lysogenic phage encoded. Erythematous rash on neck trunk and extremities that fades and is followed by extensive desquamation. Strawberry tongue.

Streptococcal TSS

Fulminant infection; shock and multi-organ failure. Begin at site of trivial trauma. 30% mortality even w/ antibiotic treatment. Associated w/ shock, necrotizing fasiitis, myonecrosis, bacteremia. “flesh-eating bacteria”

Infective endocarditis

Primarily due to oral streptococci (prev: viridans and streptococci). Account for ~70% of cases Strep and 50% of those are S. viridans. Other causes: Enterococcus faecalis, S aureus (IV drug users). Infection usually occurs on abnormal valves. Fatal w/o treatment

Subacute bacterial endocarditis

Microorganism enters blood --> heart --> lodge on heat tissue; multiply --> become trapped in blood clots. Fever --> heart murmur. Non-specific symptoms: anorexia, malaise, chills, nausea, vomitting, night sweats

Necrotizing fasciitis

Deep local invasion of tissues and tissue necrosis. Acute infection: rapid patient deteriation. Symptoms: toxic shock-like syndrome, fever, hypotension, multi-organ involvement high mortality. Local and systemic antibiotics and surgery. Polymicrobial, Streptococcal, Clostridial myonecrosis. Dark blue-red fluid filled blisteres. Pseudomonas aeruginosa.

Gas gangrene

Clostridium perfringens. Obligate anaerobe. Infection develops in areas w/ poor blood supply. Buttocks, perineum. Exogenous or endogenous (from faecal flora). Accumulation of CO₂ and H₂ in tissues. Less likely than localized cellulitis. Dead and dying tissue further compromise circulation. Fever, sweats, hypotension. Death from shock and renal failure. ~12 soluble antigens. Degradative enzymes. Alpha-toxins = lechithinase.

Naglar reaction

Clearing zone around microorganism if toxin is present.

Diagnosis of gas gangrene

Necrosis. G- organisms. Recent injury/surgery. Crepitis upon palpitation

Acne

Propionibacterium acnes. Gram + bacillus. Anaerobic. Member of normal skin flora. Found in sebaceous glands. Virulence factor: lipases hydrolyze sebum triglycerides --> fatty acids --> inflammation. Tetracycline, erytrhomycine

Leprosy

Myobacterium leprae

Cutaneous anthrax

Bacillus anthracis