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Antigenic Variation in Evasion
Chapter 27
22
Biology
Professional
02/27/2012

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Term
What are 3 types of Antigenic Variation utilized by pathogens?
Definition
1) Phase Variation (switching on or off genes that produce phenotype such as flagella in Salmonella and fimbriae in E. coli)

2) Antigenic Drift- accumulation of mutations ((error prone replicaitons)

3) Antigenic Shift- Abrupt change in surface antigen (gene conversion/rearrangement)
Term
What is Influenza Type A pathogenesis?
Definition
1) HA is essential for binding, and then is cleaved by host protease leading to endocytosis and vacuole acidification

2) Neuraminidase prevents viral aggregation and allows release of newly formed virus particles.
Term
What symptoms are associated with Uncomplicated influenza?
Definition
1) 1-2 day incubation followed by sudden onset fever, chills and headache lasting 3 days or so

2) Cough often follows (recovery can be 2 weeks)

**Fever is most important physical finding
Term
What Complications are associated with influenza?
Definition
1) Secondary bacterial pneumonia in elderly (return of fever with cough, sputum and consolidation in lung) arising from Strep. pneumo or Haemophilus influenzae

2) Croup or Exacerbation of chronic diseases (bronchitis, asthma)
Term
How do you diagnose/treat the influenza?
Definition
1) Epidemiology or throat/nasal swab

2) Treat with Amantadine/Rimantadine and Oseltamizir/Amantavir
Term
Why can't vaccine strains be given to people with severe egg allergies?
Definition
The strains are grown in chicken eggs!
Term
How does Antigenic drift occur in influenza?
Definition
1) HA and NA proteins from point mutations resulting from poor-fidelity RNA poli

2) Antibody-mediated selection
Term
How does Antigenic Shift occur in influenza?
Definition
Reassortment between 8 segmented RNAs on 2 different viruses

Ex) 1918- H1N1 shift and drift
Term
How in the "Bird flu" an example of antigenic variation?
Definition
H5N1 is carried by birds and has high probability of reasortment

- Usually wont go to humans because of sialic acid, but can go THROUGH PIGS.
Term
How does antigenic variation occur in Neisseria gonorrhoeae?
Definition
Both Phase and Antigenic Variation

1) Variable regions in Pilin protein (Ab cannot be maintained!)

Gene conversion- pilS "converted" to pilE site (from same or different organism)

- pilE locus is expression site
- pilS contains variable regions (1-6 copies per chromosome)

2) Opa
3) LOS
Term
What virulence factors are associated with N. gonorrhea?
Definition
1) Pili for attachment to columnar epithelium (non-ciliated) and subsequent penetration (site of antigenic variation)

2) Opa proteins for phase and antigenic variation (may increase adhesion)

3) LOS- Core undergoes phase and antigenic variation
Term
What Disease specifics characterize a Trypanosoma brucei spp gambiense or rhodesiense infection?
Definition
1) African trypanosomiases (sleeping sickness)

2) Flagellated parasite transmitted by tsetse fly

3) Trypomastigote form lives in blood (extracellular)

4)
- Chancre (stage 1) followed by systemic spread with lymphadenophathy, fever (intermittent, high fevers), anemia, transient edema and rash.

- CNS involvement (stage 2) with meningitis and sleeping during the day.
Term
What is the general course of a Trypanosoma brucei infection
Definition
Stage 1- Chancre followed by systemic spread with lymphadenophathy, fever (intermittent, high fevers), anemia, transient edema and rash.

Stage 2- CNS involvement with meningitis and sleeping during the day.
Term
Explain Trypanosoma bucreyi pathogenesis.
Definition
Must persist in bloodstream in order to spread- depends on antigenic variation of VSG (surface glycoprotein)

** waves of parasitemia occur because of variation**
Term
What types of antigenic variation occur in Trypanosoma brucrei infection?
Definition
VSG variation allows persistance in bloodstream.

GENE CONVERSION (mostly)

- Homologous recombination of silent VSG sequences in active expression site.

- Telomeric exchange
Term
How do you diagnose/treat sleeping sickness?
Definition
1) Blood smear for stage 1 or CSF exam for stage II

2) Drug choice depends on stage, parasite and side effects.
Term
What disease is caused by T. cruzi?

How does antigenic variation in T. cruzi compare to T. brucrei?
Definition
Chagas disease in South America

- Blood and Intracellular stage like T. brucrei
- NOT CLASSICAL ANTIGENIC VARIATION
- Evades complement
Term
What type of antigenic variation is responsible for seasonal pattern of influenza?
Definition
Antigenic Drift in HA and NA proteins
Term
What type of antigenic variation is responsible for Pandemic spreads of influenza?
Definition
Antigenic Shift occurring by reassortment of segmented RNAs within the same host (often same cell).
Term
Why can't you vaccinate against the Bird Flu?
Definition
Viruses in birds go to pigs, which have the same sialic acid form as humans.

Also, it is made in eggs!
Term
What is the basic life cycle of Trypanosoma brucei?
Definition
EXTRACELLULAR PATHOGEN

1) Epimastagotes in salivary gland transform into metacyclic trypomastigoes

2) Tsetse fly takes up blood meal and injects metacyclic trypomoastigotes into the blood, where they become trypomastigotes
Term
Why is there no antigenic variation in T. cruzi?
Definition
Intracellular stage as amastigote prevents antigenic variation.
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