this unit dealt with vaccination in all its glory; all the immunological, biochemical, ethical, developmental issues that sprout forth from it. vaccination is basically the act of injecting a small amount of inactive or inactivated antigen into the body in order to purposely create an immune response and develop immunological memory so as to be better prepared for the next encounter with that antigen. in a population, vaccination is effective because of the principle of "herd immunity"- the unvaccinated individual still has good chances of not being infected because everyone else is vaccinated. vaccines can be designed to invoke responses against different types of antigens; a b cell response would be desired for extracellular pathogen or toxins, while a t cell response would be desired for intracellular pathogen.
some developmental considerations: up until 1 year, infants can't invoke a Th1 response due to the inability of the antigen presenting cells to make IL-12, and the inability of their t cells to make IFN-gamma (they receive their IFN-gamma from breastmilk up until this point). thus, infants younger than 1 year will only invoke a Th2 (antibody) response when vaccinated. even though this is the case, it is routine to vaccinate infants within 12 hours of birth for hepatitis B, mainly due to logistical factors (cheaper, more convenient, next checkup might not be for a while).
vaccine design has to take many factors into account, such as safety, timing of administration, cost, mechanism of action, type of antigen involved, etc. there are several different ways to kill or inactivate antigen-- note that "inactivated" antigen means that the antigen can never again be pathogenic, whereas "inactive" or attenuated refers to antigen that is at the moment not pathogenic, but has the potential to be. the old method for producing inactive antigen was to simply boil the antigen- the downside to this being that immune response to these denatured proteins might be different than to the original antigen. now the conventional method is "formalyn inactivation"- a chemical inactivation.
there are other ways to prepare vaccines besides the killing / inactivation route, each with their own advantages and disadvantages. the "protein subunit" method uses just a piece of the toxin as the antigen- while this guarantees that the antigen will not be pathogenic, it also requires multiple doses to get an adequate immune response. some vaccines use just the DNA of the antigenic protein instead of the protein itself-- while this method is cheap, it doesn't work too well with humans. another method tries to make antigenic peptides that fit directly into MHC (as opposed to antigen being processed into peptides in the cell and presented in MHC)-- unfortunately, because of the lack of expression of co-stimulatory molecules, this method produces tolerance rather than immunity. finally, DC vaccines are currently in development- dendritic cells are isolated outside of the host, exposed to the antigen, then put back into the host, where they can go to the lymph nodes and initiate an immune response.
questions
definitions...
1. what is contained in a vaccine?
2. what is the difference between inactive and inactivated pathogens?
3. what is the purpose of a vaccine?
4. what is meant by "herd immunity"?
5. what are some considerations required for the design of vaccines?
6. what sort of immune response would be appropriate for an extracellular pathogen?
7. what sort of immune response would be appropriate for intracellular pathogens?
8. what sort of immune response would be appropriate against toxins?
9. what is thimersol and why was thimersol used in vaccines up until recently?
10. why is aluminum added to vaccines?
developmental issues...
11. why can't infants younger than 1 year old invoke a Th1 response?
12. what is the response to vaccination of an 6 month old infant?
13. where do infants get their IFN-gamma?
14. when is the hepatitis B vaccine generally administered and why?
vaccine preparation...
15. what is a conjugate vaccine?
16. what is an attenuated vaccine?
17. what is the CDC recommendation for the timing of the measles mumps ruebella vaccine?
18. what was the old way for killing viruses for vaccine preparation and what was its downfall?
19. what is the new way for killing viruses for vaccine preparation?
20. how is the flu vaccine formulated?
what are these types of vaccines and what are their advantages and disadvantages:
21. protein subunit
22. DNA
23. peptide
24. DC vaccines
answers
1. an inactive or inactivated form of antigen.
2. inactive can potentially still be activated (also called attenuated), whereas inactivated pathogens will never be harmful again.
3. to increase numbers of T, B cells specific for the injected antigen so as to provide immunological memory to protect against future infection.
4. the idea that the effectiveness of vaccination is proportional to how much of the population is vaccinated- or that the unvaccinated individual has less of a chance of infection because everyone else has been vaccinated.
5. type of antigen / pathway of infection, safety / toxicity, timing of administration, cost.
6. a b cell response.
7. a t cell response
8. an antibody (b cell) response.
9. it is a mercury containing component of vaccines that was used to protect against contamination of the vaccine itself- due to repeated usage of the same bottle for multiple vaccinations by doctors.
10. it enhances the antibody response.
11. their APC's can't make IL-12, and their t cells can't make IFN-gamma; CD8 t cells won't be activated.
12. this infant will produce a Th2 response.
13. breastmilk.
14. within 12 hours, mainly due to convenience, and the fact that before 2 years old the infants have a much higher susceptibility for infection by the Hep B virus.
15. conjugate vaccine is an non-protein antigen (hapten) that is combined with a protein ("carrier") in order to ellicit an immune response.
16. an inactive form of antigen which has been passed through several different animals, usually including a bird, in order to make it non-tropic for humans.
17. 18 months.
18. boil a protein to denature it- but the new protein has might produce a different immune response than the original.
19. "formalyn inactivation"
20. 3 strains of the flu are combined into one vaccine based on what strains are expected to be virulent for the upcoming season.
21. using only a piece of toxin to initiate the immune response; don't get a big immune response, so need multiple doses.
22. injecting the DNA instead of the antigenic protein; cheap but doesn't work well in humans.
23. make the peptide that fits directly into the MHC molecules; instead of creating immunity creates tolerance because doesn't cause co-stimulatory molecule expression.
24. isolating dendritic cells, exposing them to antibody outside of the body, putting them back into the body, where they can travel back to lymph nodes and initiate immune response; is still in development and very expensive.
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