USMLE STEP 1 Microbiology

Terms in this set (1048)

Generalized: Lytic virus life cycle (also temperate virus life cycle)
- produced when the phage with a lytic life cycle puts a piece of bacterial DNA into its head (packaging error; all bacterial genes are susceptible)
- all bacterial genes have an equal chance of being transduced
- "mistake-packaging" phage then infects another bacteria cell and "transduces" the unintentional pickup of the original bacterial DNA into the new bacteria cell; string of DNA requires homologous recombination and exchanges can occur
- new combinations of genes made possible through phage vector


Specialized: Temperate virus life cycle
- occur when an error is made in the life cycle of a temperate (lysogenic) phage; excision defect
- temperate phage introduce their genomic DNA into the bacterial chromosome at a specific site (lambda DNA inserts ONLy between E. coli genes gal and bio); normally excised later when ready to finish lytic cell cycle
- Excision error can occur and the bacteria next to the specific site of insertion (gal or bio; not all bacterial genes like generalized transduction) can be excised by error and encoded into the phage; lytic cycle ensues
- when this phage infects a new bacteria, previous bacterial DNA can be stabilized into the new bacterial chromosome through homologous recombination


Repressor: LYSOGENY (EDC like-Stole my Brain SOn)
- Temperate phage infects a bacteria and inserts DNA at specific site on the bacterial chromosome
- A "race" for regulatory rights occurs right when a temperate phage inserts foreign DNA into bacteria; if repressor is made quick enough then the bacterial-DNA will not go into lytic life cycle
- repressor is made and the DNA stably stays as a prophage; gets inherited through infinite generations as long as repressor is intact
- if repressor is damaged (UV, cold, alkylating agents) during reproduction then the temperate phage will finish life cycle and usually lyse bacteria = induction
- At this point the excision defect can still occur and specialized transduction can follow (as above)
Herpesvirus
Characteristics:
- Large dsDNA
- Enveloped, icosahedral
- Derives envelope from nuclear membrane
- Intranuclear inclusion bodies (due to assembly in the nucleus; diagnostic finding)
- Establishes latency

Herpes Simplex Virus 1 & 2

Reservoir: human mucosa and ganglia

Transmission
- close personal contact
- kissing, sexual contact

Pathogenesis:
- HSV establishes infection in mucosal epithelial cells
- formation of vesicles in epithelial cells
- virus travels up the ganglion to establish lifelong latent infection (CNV for HSV-1)
- Stress triggers reactivation of virus in nerve and recurrence of vesicles

Diseases: rule of thumb is HSV-1 infections generally occur above waist and HSV-2 infections generally occur below the waist
1. Gingivostomatitis and cold sores (HSV-1)
- blister-like lesions on the oral mucosa
- latent in trigeminal ganglion (CN V)
- the tingling sensation felt before blister first appear is the feeling of the latent viruses traveling anterograde in the CN-V

2. Keratoconjunctivits (rubbing cold sores then touch eye)
- generally with lid swelling and vesicles
- dendritic ulcers may be seen (fluorescent staining)
- untreated and repeat attacks may result in blindness

3. Meningoencephalitis
- HSV-1 is #1 viral encephalitis in US
- fever, headache, and confusion
- focal temporal lesions and perivascular cuffing
- untreated, 70% mortality rate (use acyclovir)
- HSV-1 high fatality
- HSV-2 usually mild

4. Genital infections (HSV-2)
- Painful genital vesicles
- Systemic effects can include fever, malaise , and myalgia
- latency in the sacral nerve ganglia

5. Neonatal herpes
- infection during passage through infected birth canal
- infections are usually severe:
a. disseminated with liver involvement and high mortality
b. meningeal encephalitis (high mortality)
c. skin, eyes, or mouth


Diagnosis:
- Oral lesions - clinical
- Encephalitis - PCR on CSF, Large numbers of RBCs in CSF
- Genital infections - Tzanck smear to show the formation of multinucleated giant cells (syncytia) and Cowdry type A intranuclear inclusions has been largely replaced by immunofluorescent staining, which can distinguish HSV1 from HSV2

Treatment: Acyclovir
- a nucleoside analog that only activates in cells infected with HSV1, 2, or VZV This is because the virus thymidine kinase is required to activate the drug by placing the first phosphate on the drug, followed by the phosphorylation via cellular enzymes.
- Resistance to acyclovir occurs due to a mutation in the thymidine kinase.
- Famciclovir, valacyclovir, and peniciclovir are alternatives if resistance develops
- Side effects rare
VZV

Characteristics:
- Large dsDNA, enveloped, icosahedral
- Derives envelope from nuclear membrane
- Intranuclear inclusion bodies (due to assembly in the nucleus; diagnostic finding)
- Establishes latency

Reservoir:
- human mucosa
- nerves

Transmission:
- Respiratory droplets
- Contact is possible but less likely (nobody gonna keep touching the vesicles)

Pathogenesis:
- VZV enters the respiratory tract
- Replicates in the local lymph nodes→1° viremia
- spleen and liver→2° viremia
- skin (rash; day 2)
- latent in the dorsal root ganglia
- reactivation occurs due to stress or immunocompromised causes vesicular lesions and severe nerve pain

Disease:
1. Chickenpox
- fever, pharyngitis, malaise, rhinitis
- asynchronous rash (all stages presents same time; macules, vesicles, scabs, etc. vs. smallpox is synchronous)
- one of the five "classic" childhood exanthems, less common due to vaccination

2. Shingles
- Zoster (seniles)
- pain and vesicles restricted to one dermatome (unilateral only!)
- fifth or sixth decade of life
- reactivation of latent infection

Complications: pneumonia + encephalitis


Diagnosis:
- Tzanck smear - Cowdry type A, intranuclear inclusions
- Antigen detection by PCR
- Syncytia present (giant cell pneumonia possible)


Treatment:
- Healthy adults with shingles - oral acyclovir
- Immunocompromised - IV acyclovir
- Aspirin contraindicated due to association with Reye syndrome (encephalitis)


Prevention:
- Live, attenuated vaccine
- VZIG (varicella-zoster immunoglobulin) for postexposure prophylaxis of the immunocompromised
EBV

Characteristics:
- Large dsDNA, enveloped, icosahedral
- Derives envelope from nuclear membrane
- Intranuclear inclusion bodies (due to assembly in the nucleus; diagnostic finding)
- Establishes latency

Reservoir: humans

Transmission:
- Saliva
- 90% of the adult population is seropositive (may not have a clinical diagnosis during primary infection due to immature T-cell response during childhood)

Pathogenesis
- Virus infects nasopharyngeal epithelial cells, salivary and lymphoid tissues
- Latent infection of B cells (EBV binds to CD21/CR2 and acts as B-cell mitogen)
- Results in production of atypical reactive T cells (Downey cells)
- Downey cells may constitute up to 70% of WBC
-*Heterophile antibodies are produced; diagnostic (due to B-cell mitogenesis; non-specific B-cells produced, NOT specific B-cell proliferation*)


Diseases:
1. Heterophile-positive mononucleosis "kissing disease"
- Fatigue, fever, sore throat, lymphadenopathy and splenomegaly (why people with mono can't play sports)
- Latency in B-cells

2. Lymphoproliferative disease (look like B-cell lymphoma)
- Occurs in immunocompromised patients
- T cells can't control the B-cell growth

3. Hairy oral leukoplakia (opportunistic infection)
- Hyperproliferation of lingual epithelial cells ("hairy" tongue)
- AIDS patients (opportunistic infection)


Malignancies
1. Burkitt lymphoma* (B-cell lymphoma of jaw)
- cancer of the maxilla, mandible, abdomen
- Africa
- Malaria cofactor
- AIDS patients (more common abdominally)
- Translocation juxtaposes c-myc oncogene to a very active promoter, such as an immunoglobulin gene promoter

2. Nasopharyngeal carcinoma
- Asia
- Tumor cells of epithelial origin

3. Hodgkin lymphoma*
- world wide


Diagnosis:
- Heterophile-antibody positive (IgM antibodies that recognize the Paul-Bunnell antigen on sheep and bovine RBCs)
- EBNA associated with transformed cells (immortal cells; carcinoma)
- Downey cells, monocytes ⬆
- Serology based on EBV viral antigens


Treatment:
- Uncomplicated mononucleosis, treatment is symptomatic
- acyclovir for immunocompromised (for lymphoproliferative)
Influenza virus A/B

family: orthomyxovirus

characteristics:
- (-)ssRNA, segmented (8), helical, enveloped
- replicate in cytoplasm and nucleus
2 glycoproteins:
- H: helps get in cell
- N: helps clip cell exit/budding

reservoir:
- A: birds, pigs, humans "A for ANIMALS"
- B: humans only
- C: insignificant

Transmission:
- direct contact
- respiratory
- 1997 H5N1 strain jumped directly from birds to humans (avian influenza)

Pathogenesis:
1. antigenic drift
- A+B
- Slight changes in antigenicity due to mutations in H and/or N
- RNA
- Causes epidemics

2. antigenic shift
- A ONLY
- rare genetic reassortment
- coinfection of cells with 2 different strains of influenza A (H5N1 and H3N2) reassortment of segments of genome
- production of a new agent to which population has no immunity
- responsible for pandemics (world-wide)


Disease - INFLUENZA/FLU (flu-like symptoms)
- Headache and malaise
- Fever, chills, myalgias, anorexia
- Younger children: Bronchiolitis, croup, otitis media, vomiting
- Pneumonia/secondary bacterial infections
- Can lead to Reye syndrome or Guillain-Barré syndrome

Diagnosis:
- rapid test (serology)
- clinical symptoms plus flu season

treatment:
1. amantadine/rimantadine: inhibit viral uncoating, oral

2. zanamivir/oseltamivir: neuraminidase inhibitors (A+B coverage; need to give 1st day or 2 of infection or else not too effective)
- zanamivir is inhaled
- oseltamivir is oral


prevention:
1. killed vaccine (predominant)
- 2 strains of influenza A (H3N2, H1N1, for example) and 1 strain of influenza B are incorporated into the vaccine

2. live, attenuated vaccine
- intranasal administration
- similar composition, recommended for children >5yrs
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