Other Infectious Agents and Vaccines

  1. Prions
    • naked protein--variants of PrPc (involved in a number
    • Interact with endogenous cellular proteins
    • form neural plaques and tangles
    • causes diseases called spongiform encephalopathies
    • Two types: TSE (transmissible) and GSE (genetic/rare)
  2. What is interesting about the variants of prions?
    the variants have a primary sequence identical to the primary sequence of normal proteins; what differs is the secondary and tertiary structure

    prions can dimerize/ acid resistant/ resistant to proteinases/ can't break them down
  3. What does PrPnaturally do?
    it naturally maintains myelin on myrlinated axons, prevents lysis from osmosis, etc.
  4. Explain Kuru
    - first observed? 
    - how obtained?
    - effects?
    - prion involved?
    • Observed in New Guinea during the 1920s
    • Ritualistic cannibalism: consumed the tissues, including brain of deceased family and battle enemies; brain tissue from individuals with kuru was highly infectious; prion was transmitted via eating or sores/ cuts

    Parkinsonian movement (6 ms-1 yr) and dementia (1-2 years)

  5. Crutzfeld-Jacob
    three types: classic, variant, familial

    • Parkinsonian symptoms
    • new: 1999-2000
  6. Classic Crutzfeld-Jacob
    • onset over age 60
    • sporadic (sCJD)
  7. vCJD
    • onset below 30
    • acquired (vCJD or iCJD); 
    • 2 years
  8. fCJD
    familial; occurs in families where genetic mutations allow them to form
  9. BSE/ Mad Cow Disease
    - first identified?
    - result of? 
    - association?
    • first infections of BSE occurred in the 1970s; two being identified in 1986
    • result of feeding cattle meat-and-bone meal that contained Scrapie/ BSE-infected material
    • Strong epidemiologic evidence for a causal association with vCJD
    • first reported from UK in 1996
  10. Viroids
    - are what?
    - infect what? 
    - reservoirs of them? 
    - related to?
    - can be used in what?
    naked nucleic acids that can be as small as 22 nucleotides

    infects damaged plants, causing color changes, wilting leaves, root rot, plant death, stunted growth; affects chloroplast; uses it as a base to begin replication

    -plant reservoirs

    - related to introns 

    two families (PSTVD/ ASBVd)
  11. What are the mechanisms of action for the antiviral drugs?
    • attachment blcokers
    • penetration and uncoating blockers
    • genome relication inhibitors
    • gene expression
    • inhibitors of assembly, aturation, and release
  12. Attachment blockers
    • viral attachment mimetic
    • - Anti-receptor antibodies
    • - Anti-idiotype antibody to viral particle
    • - Natural receptor ligands & agonists
    • - Peptides that mimic the receptor binding domains
  13. What aren't viral drugs often prescribed?
    they are unspecific and have several issues
  14. Attachment blockers
    - do what? 
    - include what?
    • mimic the receptor and bind the virus
    • anti-virus antibodies
    • receptor anti-idiotyp antibodies
    • extraneous receptor
    • synthetic receptor mimetic (sialic acid for influenza)
  15. Penetration and Uncoating
    • The drugs generally interfere with proteins
    • Two common drugs interfere with endosomal enzymes that inhibit HA conformational changes
    • Amantadine                             Rimantadine

    The capsids can't break down and uncoat/ viral components can't get out
  16. Genome Replication Inhibitors
    • These drugs are polymerase and protease inhibitors
    • Many of these drugs are nucleoside analogs
    • Pro-drugs
    • Phosphorylated for activity
    • Toxicity varies between analogs
  17. Gene Expression
    • Engineered proteins
    • Interfere with enzymes
    • Oligonucleotides
    • Bind RNA
    • Non-nucleotide RT inhibitors
    • Bind enzymes directly
  18. Assembly, Maturation and Release
    • Interfere with late stage processes
    • Tamiflu and Relenza
  19. Vaccines
    - two types
    whole agent and subunit
  20. Whole Agent
    • - live
    • - inactivated by formalin (rabies, salk polio)
    • - attenuated: replicate a very mild case; agent replication increases the dose; mutation issues; reuces the virulence of the pathogen
  21. Subunit  Vaccines
    - what are the four
    erecombinant: protein or portion expressed in a vector (Hep B)

    toxoid: inactivated toxin (tetanus/ diptheria)

    conjugated: immunogenic molecule fused to a protein (strep pneumonia)

    acellular: fraction organisms (pertussis)
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Other Infectious Agents and Vaccines