(19) Vaccination Flashcards
(41 cards)
What is Variolation?
- what disease was this used for?
Variolation - dried pustules of people with small pox were collected and used to scratch the skin of unaffected individuals in order to evoke an immune response
How was the 1st smallpox vaccine formulated?
- Cowpox has similar surface determinants as the small pox virus
- Exposure to cowpox elicits Neutralizing Abs. that are can also be used for small pox
What was the morbidity rate of smallpox?
25% of people infected died
What is the major difference in how your immune system responds to a live attenuated virus vs. a killed virus?
- why is this the case?
Live Attenuated:
- Triggers an MHC class I response
- This is because the virus actually infects the cell a produces proteins inside that can be imported and present via TAP-1/2
Killed:
- Triggers an MHC class II response
- Only APCs can take this up and present it
What immunological effects (as far as cells provoked) must be considered when designing a vaccine?
You must consider if neutralization or if T cell mediated responses are more important
Why is polio best prevented by a vaccine elicits a primarily humoral response?
Polio infects neurons which express very little MHC class I, and no MHC class II (obviously) so its important to make sure the virus never gets to the neuron or its chances of getting detected by T cell mediated immunity is slim
On first administration of a vaccine, what happens when the level of injected vaccine get too high?
Immunogenicity of the Vaccine actually Decreases
On second administration with a constant amount of vaccine to a group that had originally been given the following vaccine doses, what do you expect to see for:
- Really low doses
- Low doses
- Medium doses
- High doses
Really Low Doses:
- The body actually responds by KILLING T-cells that were differentiated to react the the virus the first time
Low Doses:
- Very little Response seen
Medium Doses:
- The cell population that was differentiated off of the first administration increases to very high levels
High Doses:
- Responding cells are killed because the body know that there is too much antigen around for this to be an infection
T or F: for a vaccine to be most effective it must be injected
False, the most effective method to administer is the one that most closely resembles the original route of infection
What is the problem with giving vaccines for diseases such as the flu parenterally (IV, IM, Sub-Q)?
- what about giving it via mucosal route?
- Mucosal Antibodies for the virus are not created this way
- In contrast if the vaccine is given in the mucosal route then it covers for BOTH Mucosal infection AND Systemic infection
If you must give a vaccine via Parenteral administration, methods of parenteral administration will you want to try first, second, third, and last?
Subcutaneous > Intraperitoneal > Intramuscular > Intravenous
What immune Response is typically primed by live attenuated viruses?
- MHC type?
- cell type?
- MHC class I presents to CD8 cells
- TH0 is pushed to TH1 cells
**Note the same goes for an intracellular bacteria
What T cell is is favored in response to extracellular pathogens?
TH2 - vaccines that remain extracellular will push the response to this type
- Drives ANTIBODY production (IgA, IgE, IgG2, IgG4)
What is the problem with administering a vaccine that does not evoke “danger” signals?
- No danger signals = no B7 upregulation via the PRRs and APCs
- Additionally cells that bind T cells that bind MHC when do B7 is present become anergic and die
**Without B7 no immune response can be generated no T cell activation => no B cell activation => 0 response
T or F: while a vaccine may elicit an immune response, that immune response may not be protective
True, this is a waste of energy and cell space to mount a response to antigens that are not representative of what is seen on the bug
What is a whole pathogen vaccine?
- example?
- Whole Wild-Type bug can be used (cowpox for small pox)
- Attenuated bug can be used
**Polio Vaccine is the prime example of using the whole thing
What is a subunit vaccine?
- Purified components
- Mixtures of Pathogen-Derived Antigens
- Can be recombinant forms of pathogen components or engineered into delivery vector organisms
Which is better whole pathogen or subunit vaccines?
Different Formats depend on what type of Response is needed
What is an adjuvant?
Material that MUST be co-administered with the vaccine to ELICIT an IMMUNE RESPONSE so that B7 can be upregulated and the vaccine can be effective
What are common features of all of the Freund’s Adjuvants?
- what are they made of?
- how are they typically administered?
- are these used in humans?
**When mixed with antigen these form a paste like substance that releases antigen slowly over a couple of weeks
Made of:
Oil and Water Emulsion
Administered:
Subcutaneously
NOT used in Humans - too many side effects
Compare Freund’s incomplete adjuvant to the complete and MDP adjuvants.
Complete and MDP adjuvants include Mycobacterial PAMPs that can be recognized by APCs and cause B7 upregulation
What adjuvants are used to push antigen presentation mostly to the MHC class II pathway? - what is another common feature of these adjuvants?
Freund’s Adjuvant
Alum
MF59
***these all form Depots allowing for slow release from the site of injection
What is Alum?
Alum is not terribly effective, so it is often paired with what to make it more effective?
Alum - Aluminum Hydroxide Gel
Alum can be paired with Bordetella pertussis to bind to PAMPs and promote co-stimulation needed to activate T cells
Suppose you want your vaccine components to get presented on MHC class I. What Adjuvant should you use and why?
ISCOMs (immune stimulatory complexes) are your best bet because they are MICELLES that FUSE with the cytoplasmic membrane of cell INCLUDING APCs
**This allows for presentation via the MHC class I pathway
