Glossary of micro joint 1
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- What are the characteristics of bacterial chromosomes?
-Borellia spp linear
Organized into ~ 50 domains
~1 mm long (500x length of the bacterium)
Domains are supercoiled (implications for gene expression, esp. virulence genes)
- Extrachromosomal genetic elements
Capable of autonomous replication
- lysogenic conversion
- refers to when a nonvirulent strain of bacteria acquires a prophage encoding a virulence factor and therby converts to a virulent strain
- What is the defining factor about transposons?
- cannot replicate autonomously-Must be integrated into a replicating molecule (chromosome, plasmid or virus) to be maintained
- IS element transposon
- major cause of bacterial mutation
catalyze DNA rearrangments(deletions, inversions, and replicon fusion)
- What is necessary for a stable genetic exchange?
- integration of the DNA fragment into the bacterial chromosome or plasmid via recombination
- Uptake of DNA from the environment!!!
DNA bound by specific receptors and transported into the cytoplasm, one strand being degraded (Haemophilus, Bacillus)
May require specific DNA recognition sequences (Neisseria)
- Transfer of DNA from donor to recipient requiring cell-cell contact!!!
Usually involves participation of a conjugal plasmid
- Conjugal plasmids
- Carry a set of genes necessary for conjugal transfer of DNA
Transfer begins at a specific site on the plasmid, the origin of transfer, and proceeds by rolling circle replication
- Forming mating pairs in Gram NEGATIVE(Ecoli)
- Sex pilus contacts recipient
Pilus retracts bringing donor and recipient into close contact
Formation of mating pore allowing transfer of DNA
- Forming mating pairs in Gram Positive(E.faecalis)
- Recipient secretes peptide pheromone to attract donors
Mating aggregates form
- Hfr transfer
- Conjugal plasmid integrates into chromosome
Transfer begins within integrated plasmid
Chromosomal DNA transferred to recipient
- F prime plasmid formation
- Occasionally an integrated plasmid excises carrying a fragment of chromosomal DNA
This F’ plasmid can transfer to recipient cells
The chromosomal fragment is maintained as part of the plasmid
No recombination with the recipient chromosome is required
- Packaging of bacterial DNA into a viral particle
- Conjugative transposons
- Move from one site in the DNA to another – transposition
Move from donor to recipient during transposition – conjugation
- What is diauxic growth?
- ability of bacteria to preferentially use feul in an enviornment of multiple feuls
- How does inducer exclusion work?
- when glucose enters cell it is phosphorylate leaving a lot of IIeGLU that inhibits lactose permease
- What happens in the absence of glucose?
- Phosphorylated IIeP activates adenylate cyclase which produces cAMP which activate the lac operon via CAP
- Describe global regulation of CAP
- CAP works on many operons when activated but specific signals causes requisite catabolic genes.
- Nitrogen uptake
- glutamine synthetase converts NH3 and glutamate into glutamine in an ATP dependent reaction
- How is glutamine synthetase transcription activated?
- When there is a high ration of a-ketoglutarate/glutamine ration, NtrC is phosphorylated and activates transcription via sigma54
- heat shock
- sigma 32 activates genes which either refold of degrade unfolded proteins
- how do bacteria monitor its population and environment?
- through a general signal AI-2 and a species specific signal AI-1.
- single stranded DNA virus
- double stranded DNA virus
- RNA + virus
- RNA - virus
- Double stranded RNA virus
- Course of disease
- Acute-common cold
- Parvovirus examples
- Papovirus examples
- Herpesvirus examples
- Poxvirus examples
- What are the features of virus used in classification
- virus genome structure
presence/absence of envelope
- Which viruses are enveloped?
- DNA-pox, herpes, hepadna
- Which viruses are not enveloped?
- DNA-parvo, papova (polyoma, papilloma), adeno
- Characteristics of parvoviridiae
- -replicate autonomously
-require cell to enter S phase of cell cycle for virus replication
-Only single strand DNA virus with + or - strand polarity
-B19 is the known only disease causing infectious family member in humans
- B19 replication
- -repilicates in RBC precursor
-genome has hairpin that act as primers for DNAP
-duplicated and transcribed in nucleus
-CAP and genome form caspid which is released upon lysis
- Pathogenesis of B19
- -mainly erythema infectiosum (“slapped cheek”, “fifth disease”)
-associated with arthritis
-Primary infection in 2nd trimester may manifest as fetal hydrops – severe fetal anemia causing cardiac failure with associated edema
- What patients can B19 cause aplastic crisis and chronic anemia?
- aplastic-sickle cell, thalassemia
- What is the treatment for B19 induced fetal hydrops?
- watchful waiting
high dose IG
intrauterine fetal transfusion
*no prophylaxis available
- -polyomaviruses are able to manipulate host cell cycle to facilitate virus replication
-encode large T antigen, that is able through inactivation of pRB and p53.
- T antigen
- -helicase activity
-inactivates tumor suppressors
-tricks cells into entering S phase to aid viral replication
- Human Polyoma Virus
- -BK, JC
Epidemiology -aquired during childhood
Pathogenesis-reactivated or primary infection during renal transplants can cause severe infection
- Progressive multifocal leukoencephalopathy (PML)
- Demyelinating disease, associated with 2-4% of AIDS patients
caused by polyoma virus
- Transmission - direct contact
Primary infection - infects basal layer of epithelial cells
Latency - remains in basal epithelium
Reactivation - normally causes warts(virus forces warts to divide--tumor possible)
- Tumor transformation in HPV
- -viral genome disrupts E2 upon insertion which control E7-pRB binding
-E7-pRB binding helps release control of cell cycle
- Common Wart
- Members: HPV 1,2,4
Transmission: direct contact
Penetration: break in dead cell layer
Organ affected: skin
Clinical significance: common and superficial
- Flat (planar) Warts
- Members: HPV 1,3,4,9,10
Transmission: direct contact
Penetration: break in dead cell layer
Organ affected: skin - usually hands and feet
Clinical significance: nuisance and difficult to remove
- Laryngeal HPV
Transmission: during birth
Penetration: none required
Organ affected: exposed epithelial cells of larynx
Clinical significance: grow rapidly, may affect speech, can be life threatening if airway becomes blocked
- Epidermodysplasia Verruciformis
- rare disease that is thought to involve an underlying dysfunction in cell mediated immunity (autosomal recessive)
warty papules and plaques
- Gentital Warts
- Members: HPV 6,11,16,18
Penetration: break in dead cell layer
Organ affected: skin - genital area
Clinical significance: nuisance with occasional malignant conversion (HPV16,18)
- What percentage of cervical cancer is associated with HPV?
- HPV Tumor associations
- 5,8-skin carcinomas in EV pts
16,18,31,33-genital tract cancer
6,11-malignant prog. of respiratory carcinomas
- Adenovirus replication
- drives infected cell's cycle via E1A which binds to inactivate pRB and E1B which binds to inactivate p53
- What is important about adenovirus' complicated replication?
- many levels to target therapies
- Transmission - aerosol, close contact, possibly oral-fecal
Primary infection- epithelial cells of mucous membranes of respiratory tract, gastrointestinal tract, or cornea/conjuctiva
Persistent (latent?) infection in lymphoid tissues (tonsils, adenoids)
- epidemic keratoconjunctivitis (shipyard eye)--adenovirus
- Virus serotypes: Ad8
Symptoms: tearing, inflammation, corneal infiltrates (can cause lasting visual impairment)
- conjunctivitis, pharyngo-conjunctival fever--adenovirus
- serotypes: Ad3, Ad7
Symptoms: mild pharyngitis, sore throat, mild inflammation of conjunctiva
Inadequate chlorination of swimming pools
- infant respiratory disease--adenovirus
- serotypes: Ad1, Ad2, Ad5, Ad6
Symptoms: fever, aches, sore throat, cough
- acute respiratory disease (ARD)--adenovirus
- serotypes: Ad4 and Ad7
Symptoms: headaches, cough, pharyngitis, fever
Treatment: oral live virus vaccine
Only available to the military
- Waht are the three classes of herpes virus?
- Alpha-herpesviruses (neurotropic)
- HSV 1
- How long do herpesvirus infect their host?
- Herpesvirus latency
- -limited viral gene expression
-Viral genome exists as an episome in the nucleus of infected cell
-upon stimulation virus undergoes reactivation
- Distinctive characteristics of alpha herpes
- -acute disease of epithelial tissues
-latency in sensory ganglia
-recurrent infections of epithelial tissues result in lesions
- -high prevalence
-transmitted by close contact
-causes mild epithelial lesions
-can cause encepalitis, neonatal herpes
-leading cause of blindness in US
- HSV-1 primary infection
- -Usually cold sores
Sore throat, fever, and -encephalitis (rare) are also seen
-Less frequently found as a genital infection
- HSV-1 Latent infection
- -Asymptomatic – little or no virus or virion proteins produced
-Viral DNA resides in sensory neurons of (usually) trigeminal ganglion
- HSV-1 Recurrent infection
- Virus replicates and travels down sensory nerve fiber to infect epithelial cells around the nose and mouth
Symptoms are usually a milder form of primary infection
- -typically transmitted by sex
-usually causes relatively mild epithelial lesions
-can cause encephalitis
-major cause of neonatal herpes
- HSV-2 primary infection
- Usually vesicular eruptions on the genetalia
Spread by sexual contact
Affects both sexes
Less frequently found as herpes labialis (cold sores)
- HSV-2 Latent infection
- Little or no virus or virion proteins produced
Viral DNA resides in sensory neurons of (usually) sacral ganglia
- HSV-2 Recurrent infection
- Milder outbreak, usually in same location in genital area
- Varicella Zoster virus (VZV)
- Transmission is by close contact with vesicle fluid, and probably by an aerosol/respiratory route
- Varicella Zoster primary infection
- Infection occurs in seasonal epidemics as chicken pox (Varicella)
Contracted from another infected individual, usually a child
Systemic infection resulting in a generalized, vesicular rash
- Varicella Zoster Latent infection
- Asymptomatic with no virus or virion proteins produced
Viral DNA resides in cells of sensory ganglia
- Varicella Zoster Recurrent infection
- Virus travels down sensory nerve fibers and infects epithelial cells enervated by the fiber
Infections are unilateral, painful vesicular eruptions localized to the dermatome, usually in the head or upper trunk
Severe systemic infections are observed in immunocompromised individuals
- Herpes B virus
- Herpes simplex of old world monkeys
Transmitted by bites; seen in animal handlers
80% fatality rate, causes encephalitis
- Distinctive characteristics of beta herpesvirus
- -Primary infection is usually asymptomatic
-Latency in lymphoid tissues ?
-Recurrent infection is usually asymptomatic (?)
-CMV can cross placenta and cause congenital birth defects
- Infection ages 0-5 or >18
US seroprevalence 50%, worldwide >90%
Transmission by contact with virus in secretions, particularly breast milk
- CMV pathogenesis
- -when infected by breast milk, asymptomatic
-can be transmitted transplacentally during primary or recurrent infection of mother
-leading infectious cause of congenital birth defects in US
-primary infection of adults can cause infectious mononucleosis (EBV is most common cause of IM)
-AIDS: disseminated infections, including pneumonia, gastroenteritis, encephalitis, and retinitis
- CMV primary, latent, and recurrent infection
- Primary infection: epithelial tissues of oral mucosa, possibly STD
Latency: site unknown, probably macrophages
Recurrent infection: virus shed from saliva, urine, vaginal secretions, semen, breast milk, and feces
- -Infection-children 0-2 years
-primary infection causes exanthem subitum (roseola)
-site of latency unknown; reactivation not associated with any known disease
-recent association with non-HSV viral encephalitis
- Infection 2-10 years
US seroprevalence >70%
Pathogenesis-recent association with non-HHV6 rash in children
- Distinctive characteristics of gamma herpes virus
- Latent infection of B cells + other cell types??
-EBV: infectious mononucleosis
Recurrent disease asymptomatic
Associated with several cancers
- Infection-early childhood or late teens/early 20s
Transmission-contact of oral mucosa with saliva containing virus
- EBV Pathogenesis
- primary infection usually asymptomatic in children; causes infectious mononucleosis in ~50% of adults
associated with several cancers in immunocompetent hosts
major problem in transplant patients, cause of malignant B cell lymphomas
AIDS: oral hairy leukoplakia
- EBV primary, latent, and recurrent infections
- -Primary infection in epithelial cells of oral mucosa, followed by infection of B lymphocytes?
-Latency in B lymphocytes
-Reactivation results in virus shedding in saliva
- EBV associated tumors
- Endemic Burkitt’s lymphoma (100%)
Nasopharyngeal carcinoma (100%)
Hodgkin’s lymphoma (30-50%)
Lymphoma in immunosuppressed patients (~50%)
Breast cancer ???
- KSHV (HHV-8)
- gamma Herpesvirus, found in Kaposi’s sarcoma of AIDS and non-AIDs patients
tightly associated with a rare B cell lymphoma, peritoneal effusion lymphoma (PEL), that occurs in AIDS patients
- -Largest and most complex viruses known
-Oval or “brick-shaped” particles 200-400 nm in length
-Extracellular virus contains 2 membranes (EEV – extracellular enveloped virions)
-Intracellular particles only have an inner membrane (IMV – intracellular mature virions)
- Poxvirus replication
- -poxviruses replicate in the cytoplasm(unique for DNA virus
-Encodes all the necessary replication and transcription enzymes to autonomously replicate
-early and late gene expression
- human infections of the poxvirus
Molluscum contagiosum-warty papule
- Small pox (variola virus)
- Epidemiology: last natural case of smallpox was diagnosed in 1977
Source: only from close contact with infected persons
No animal reservoir or vector
No latency in humans
Spread: via droplet infection of pharyngeal secretions (ulcers in pharynx)
Incubation: 10-12 days
- Major illness caused by small pox
- rather similar to severe chicken pox
Abrubt onset of fever and prostration with macular rash on the third day
Progresses to vesicles which become pustular, ulcerated, scabbed, healed with scarring (“pock marked”)
- what are the two varieties of small pox?
- Variola minor 1% mortality
Variola major 5- 30% mortality
- Small pox vs. chicken pox
- fever 3 days before rash, slow development, centrifugal distribution, common on palms and soles
- What is severe small pox like?
- In severe disease patients became very toxemic and
- massive inflammatory response (cytokine release)
- capillary leak -> intravascular depletion
-multisystem organ failure
- which has the most serotypes and what does this mean?
- rhinoviruses have so many serotypes that it is hard to create a vaccine for it
- what are the different types of enteroviruses?
- Host range-Human viruses, no natural reserviors
-Asymptomatic infection common
-Primarily fecal-oral route of transmission, but examples of respiratory route exist
Pathology-Cause a wide range of syndromes
- Poliovirus infection
- 90% asymptomatic
5% abortive - febrile illness - headache, sore throat, fever, malaise, vomiting
1-2% Non-paralytic poliomyelitis
- Salk polio vaccine advantages
- dead virus
good systemic immunity
- Salk polio vaccine disadvantages
- multiple IM injections
*less intestinal immunity
- Sabin polio vaccine advantages
both systemic and intestinal immunity
- Sabin polio vaccine disadvantages
- neurovirulent revertion
- OBSTACLES FOR POLIO ERADICATION
-Long-term shedding of live vaccine viruses in immunocompromized individuals
- -Major cause of mild upper respiratory tract infection
-Temperature sensitive - 33°c
-Affects all age groups
-No vaccine - >100 serotypes
-No effective treatment
- -Second most prevalent cause of the common cold
- -Epidemic gastroenteritis
-Most important cause of diarrhea in adults
-Short duration, self-limiting
- How fast do you see symptoms after ingestion of Norwalk virus?
- 24 hours
- Negative sense RNA genome
RNA replication in nucleus
- What are the three types of Influenza?
- -Influenza A - 8 segments - humans, birds, pigs, horses, and aquatic mammals can all act as hosts
-Influenza B - 8 segments - humans
-Influenza C - 7 segments - humans
- Influenza A
- viruses generally cause greatest disease problems
- Influenza B
- causes similar disease symptoms and during occasional years are the most prevalent
- Influenza C
- causes mild disease symptoms by comparison
- hemiagglutin (HA)
- -responsible for initial interaction and plays role in uncoating the virus
-change in structure required to bind to membrane-due to fusion pH
- Neuraminidase (NA)
- occurs at the end of cycle and plays a role in release of the newly formed virus
- protein channel that allows H+ in cell that lowers the pH and activates HA
- who dies from the flu?
- old and young
- da FLU illness
Secondary bacterial infection and pneumonia can seriously increase consequences
- when do you see the flu and how many people are affected?
- winter months
10% of the population
- What is the incubation time for the flu?
- Brief incubation period, ~2 days abrupt onset
2 - 5 days of maximum illness
- What types of immune response does the flu trigger?
- What are some serious complications of the flu?
- secondary bacterial infection
primary viral pneumonia
CNS, muscle involvement
- What are the major contributors to pathogenesis of flu?
- 1. aerosol inoculation
2. replication in respiratory tract
3. desquamation of mucus secreting cells
- How do you detect flu early?
- lab methods that detect virus in respiratory secretions
- Why is it advantageous for the flu to occur in aquatic waterfowl?
- Continuously circulate, many of the birds are migratory
Do not cause disease
Perfect natural reservoir
- What flu subtypes have caused pandemics in humans?
- H1 subtype - 1918 pandemic (h1n1)
H2 subtype - 1957 pandemic (h2n2)
H3 subtype - 1968 pandemic (h3n2
- Antigenic drift
- Mutation in surface proteins that enables virus to escape from currently circulating antibodies
- Antigenic shift
- Reassortment of segments of the viral genome
- What is the mechanism of reassortment in flu?
- duck and human virus combine in flu to make new strains in pigs that are transmitted to humans
- 1997 AVIAN INFLUENZA
- Limited outbreak in hong kong
18 confirmed cases
All required hospitalization
- 2004 H5N1 outbreak in southeast Asia
- Highly pathogenic
238 human cases confirmed - vietnam, thailand, china - 139 fatalities
Direct transmission from birds
Killed wild birds as well as chickens
Human incidence decreased recently
- Why did the human incidence of H5N1 decrease recently?
- Decrease in host population? - >100 million birds died due to natural exposure or slaughter
Normal decline due to seasonal variation
- Defining Characteristics of Retroviruses
- -2 enveloped RNA virus
-virion associated RT
-DNA Provirus integrated
-rapid evolution via error prone RT
- what are the three main genome segments of HIV?
- Which genome segment is a target for therapy?
- pol- contians the top 3 targets for therapy RT, integrase, and protease
- What genes do the env segment give rise to?
- gp120-glycoprotein on the envelope
these would be primary targets for a vaccine
- Flow of Genetic Information in Retroviruses
- virion rna is reverse transcibed into provirus which is subsequently integrated into the genome. From here, everything is transcribed and such.
- Simple Retroviruses
- Contain only gag, pol, (pro) & env protein coding regions
e.g. Avian Leukosis Virus (ALV)
- Complex Retroviruses
- Contain additional accessory genes
Multiple mRNA splice sites
*ALL human retroviruses are complex
- which retroviruses are responsble for human t cell leukemia?
- HTLV-I, II (complex)
- What genus is the HIV virus?
- What types of disease can retrovirueses cause?
wasting and auto-immune diseases
immunodeficiency syndromes aplastic & haemolytic anaemias
- what are the four human retroviruses known?
- HIV I-AIDS
HTLV-1-T cell leukemia, tropical spastic paraparesis
HTLV 2-no known pathology
- what triggered the discovery of human retrovirus?
- ability to culture t cells in vitro-1980
- What do all human retroviruses infect?
- CD4 T cells
- T-cell leukaemia/lymphoma
- -Aggressive tumour of CD4 -cells infiltrates skin & brain
-only produced after a prolonged latent period. -Malignant change is the result of viral genome insertion changeing gene reg.
-Less than 1% develop this malignancy.
- Tropical spastic paraparesis
- Aggressive non-demyelinating spastic paraparesis.
- Epedemiology of HTLV-1?
- -Japan,Caribbean, West Africa
-prevalence increases with age
-spread via blood transfusion & sexual intercourse, breast feeding
- How do you diagnose HTLV-1?
- HTLV-1 specific antibody, ELISA
- Lentiviruses & Persistence
- ability of these viruses to evolve in response to biological, immunological & pharmacological selective pressures with a remarkable array of genetic & antigenic variations
- How does the HIV envelope allow it to escape from effective antibody response?
- sequence evolution
sheilding of receptor binding sites
- Gp120/ CD4/ Co-Receptor Interactions
- gp120 binding sites are block for both CD$ and chemokine
- Which viruses are responsible for the HIV epidemics?
- HIV-1-SIV Chimp
HIV-2-SIV sooty mangabey
- HIV Transmission
- Inoculation in blood
Perinatal transmission (intrauterine and brestfeeding)
- What is the main predictor of risk of transmission?
- HIV load
- When is infectivity highest?
- primary infection - high viremia
- What factors enhance transmission?
- Ulcerative STDs & lack of male circumcision
- What are the stages of HIV infection?
- What cells does HIV target?
- Th cells
dendritic cells-capture and present HIV
chemokine receptors CCR5 and CXCR-4
- CCR5 ligands
- RANTES, MIP-1a, MIP-1b
Homozygous mutants of CCR5 are resistant to infection
- CXCR4 ligands
- what are the main sites of HIV replication?
- Primary Lymphoid Organs
Secondary Lymphoid Organs
- What are circumstances of immune activation that faciltate HIV replication?
- proliferation of CD4 cells is a requirement for RT and nuclear transport
upregulation of CCR5 and enhanced expression of provirus in activated t cells
- What things can you use to test for HIV
- how can you test for antibodies?
Confirmation by Western Blot
Traditionally done with serum; may be done with saliva
- how can you test for antigens?
- ELISA based assay for p24 which is detected in blood before antibodies
used with ELISA to screen lood supply
- how can you test for virus?
- Quantitative RT-PCR(standard)
Qualitative PCR for DNA
Virus isolation by culture used infrequently
- How would you recognize a primary HIV infection?
- symptoms of influenza infection or acute mononucleosis
high transient viremia
- What resolves the primary peak in the primary infection and how long does it last?
- peak is resolve by CD8 cells
antibody response in 3-5 weeks
Quasi-steady state set-points in viral load are reached in 3-12 months
- After seroconversion, what predicts variable progression to AIDS?
- set point HIV RNA values
- What is the relationship between CD4 count and HIV replication?
- What is the clinical importance of viral load measures?
- strongly predictive of disease progression
standard of care for decisions regarding initiation of therapy
essential for monitoring therapy
- Clinical ‘Latency’ Period
- Approximately constant viral loads
CD4+ T cells decline slowly
No apparent symptoms
highly dynamic state with high levels of turnover
- How long does is take on average for people to progress to AIDS?
- about 10 years
- when do you see onset of symptoms and what are they?
- What do you see with full blown AIDS?
- Protozoal indicators of AIDS
- Toxoplasmosis of the brain
Cryptosporidiosis with diarrhea
Isoporiasis wih diarrhea
- Fungal indicators of AIDS
- Candidiasis of the esophagus, trachea, and lungs
Pneumocystis carinii pneumonia
- Viral indicators of AIDS
Progressive multifocal leukoencephalopathy
Hairy oral leukoplakia caused by EBV
- Bacterial indiators of AIDS
- Mycobacterium avium (MAC) Tuberculosis
Pyrogenic bacterial infections
- OPPORTUNISTIC NEOPLASIAS indicators of AIDS
- Kaposi’s sarcoma
Primary lymphoma of the brain
Other non-Hodgkin’s lymphomas
- Other indicators of AIDS
- HIV wasting syndrome
Lymphoid interstitial pneumonia
- What are the most likely indicator conditions in AIDS?
- Severe HIV-related immunosuppression-85
HIV wasting syndrome-8
M. Tuberculosis infection-3
- How does HIV directly cause AIDS?
- Lysis of infected cells(virus effect)
- How does HIV indirectly cause AIDS
- Host response-
-Apoptosis of bystander cells
-Impaired T cell regeneration
-Disruption of lymph nodes
-CTL killing of infected cells
- How much is virus turnover in the clinical latency period?
- 10^10 virions produced each day
- Besides CD4, what are the other immune perturbations in HIV?
- CD8 T cell activation: inc. CD38, dec. CD28
Apoptosis of CD4 and CD8 T cells
Naïve T cell loss, effector memory T cell increase
Altered lymph node, thymus and bone marrow
Altered T cell kinetics: inc destruction, dec. production
- What is the exception to CD4 count and viral load being inversely related?
- SIV infection in sooty mangabeys the CD4 count stays high regardless of high viremia
- What leads to increased destruction of CD4?
- direct effect of virus and increased bystander cell death as a result of inappropriate apoptosis
- Anti-HIV immune responses
- Total antibody
Inhibition of viral entry by b-chemokines
Pro-inflammatory cytokines (IFN-g, TNF-a)
- Basic Principle 1
- Infectious diseases are caused by microorganisms that differ from us both structurally and functionally
- Basic Principal 2
- Structural and functional differences of microbes provide targets for antimicrobial chemotherapy
- Koch’s postulates
- Isolate the pathogen in pure culture
Introduce the pathogen into a susceptible animal host and observe the disease
Isolate the pathogen in pure culture from experimentally infected animal
Always isolate the pathogen from humans with the disease
- Koch’s molecular postulates
- Phenotype should be more often associated with pathogenic strains of a species
Specific inactivation of the gene should decrease virulence or result in loss of a property in a cell or animal model system
Restoration of the wild-type gene restores virulence
- What is the leading cause of bacterial meningitis in the United States ?
- Streptococcus pneumoniae
- Which form of bacterial meningitis shows the highest mortality in the US?
- Streptococcus pneumoniae
- How do we identify bacteria?
-streptococci-division in one plane and grows in chains
-staphylococci-division in multiple planes
-bacillus anthracis-appear as single rods
-listeria monocytogenes-oval coccobacilli
- Gram Stain
- 1.crystal violet
3. alcohol wash
+ dark blue
- Acid fast stain
- Red dye carbol fuchsin applied to fixed smear
-Acid fast organisms retain dye because it is more soluble in the cell wall lipids than in the acid/alcohol mixture
- Acid fast stain is used to identify which bacteria?
- mycobacteria spp.
- What are hemolysis reactions?
- performed by doing a liquid or solid culture onto a petri dish and checking for a response.
- “alpha” hemolysis
- Green due to the production of biliverdin from heme. S. pneumonia will give this result
- “beta” hemolysis
- The complete lysis of RBCs around the colony
- “gamma” hemolysis
- absence of any hemolytic activity
- selection test
- selects for particular bacteria of interest and selects against those that we don’t care about (ex: antibiotics in the media that kill sensitive bacteria while resistant bacteria grow)
- Differential/selection for S. aureus
- Mannitol salt agar has a very high concentration of NaCl so that only Staphylcocci grow.
To distinguish S. aureus from all of the other Staphylococcal species add mannitol (a sugar) and a pH indicator. S. aureus will ferment mannitol while secreting lactic acid causing the pH to become acidic and the indicator will change color (from red to yellow). On the left is S. aureus and on the right is some other type of Staphylococcal bacteria.
- MacConkey agar
- Bile salts select for growth of enteric bacteria, lactose plus pH indicator identify lactose fermentation (red) indicating Escherichia coli
- Polymerase chain reaction
- rapid and sensitive identification of bacteria without having to do a culture.
Can be done for speices or strain
Also can be used to compare sequences
- DNA – DNA hybridization
- defines bacterial species
If DNA preparations from two bacteria show 70% hybridization and half the hybridizing DNA melts within a 5°C increase in temperature, the bacteria belong to the same species
- virus definition
- -Sub-microscopic, obligate intracellular parasite
- small (200-400 nucleotides) circular RNAs with a rod-like secondary structure which possess no capsid or envelope and are associated with certain plant diseases
- satellite viroid-like molecules, slightly larger, which are dependent on the presence of virus replication for multiplication, which allow them to be packaged into virus capsids as passengers
- infectious agents believed to consist of a single type of protein molecule with no nucleic acid component (e.g., Creutzfeldt-Jakob disease)
- viral capsid
- encloses viral genome
protects genome from physical(shear), chemical(UV), and enzymatic damge(nuceases or antiviral).
protein subunits are redundant
- outer envelope
- lipid bilayer containing viral glycoproteins (and in some cases cellular glycoproteins – e.g., HIV) – however, many viruses lack an envelope
- outer surface
- involved in binding/recognition of the host cell
- viral structure is icosahedral
- naked viruses tend to be stable and to resist dessication, acid, and detergent
Geometry determines the size of the genome that can be packaged inside the capsid
- What determines viral classification?
- morphology including size, shape, capsid symmetry, envelope, and viron properties
- What are the top two factors to classify a virus?
- what is the difference between positive and negative RNA?
- negative contains the complement RNA and must be copied by a viral RNA plymerase in order to produce mRNA
- Which DNA viruses have an envelope?
- Which DNA viruses are NAKED?
- Which RNA viruses have an envelope?
- Which RNA viruses are NAKED?
- Which RNA virus has a double capsid?
- What are the stages of viral growth?
- Why would catheterization predispose to infection?
- Provide access to defended site, introduce infecting organisms, block defenses
- Where did the infecting microorganisms come from?
- Normal flora, nosocomial infection
- What is sepsis and what is its cause?
- Clinical condition due to systemic effects of inflammatory responses, bacterial toxin esp. endotoxic products
- How does sepsis cause death?
- Vasodilation, DIC, organ failure
- How did the pope die?
- Organ failure due to sepsis following urinary tract infection
- Virulent bacteria
- Have the capacity to grow at the expense of the host
- Opportunistic bacteria
- Exploit preexisting conditions in the host
- Virulence factors
- Enhance the ability of the bacteria to cause disease
Not all strains of a particular species express the same virulence factors
- what factors prevent entry and spread of bacteria?
- Integrity of skin
Secretions (lysozyme, bile)
- What factors affect colonization, adhesion, and invasion?
Invasins/manipulation of actin cytoskeleton
- what determines the disease a bacteria causes?
- how the bacteria gained entry and where it ended up
- How does bacteria cause tissue destruction?
- Hemolysins, lipases (membranes)
Collagenase, protease, hyaluronidase (CT)
Provision of nutrients?
- Is LPS an endotoxin or exotoxin?
- Is diptheria toxin an endo or exotoxin?
- How does diptheria toxin cause disease?
- b unit allow translocation where the catalytic subunit A causes cell death by inactivatiing EF-2
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