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Immunology: on Vaccines

Treating the Immune System and Vaccines
Zwickey notes
Study Questions:
1. How do pathogens spread?
2. Name 3 ways in which pathogens cause disease.
3. Where are neutrophils located in a healthy person?
4. How do your natural killer (NK) cells avoid killing your own cells?
5. How do cytokines cause a systemic response?
6. What is a germinal center?
7. What two ways can you get class switching of an antibody?
8. Why is mercury put into vaccines?
9. What is the immunological basis for waiting until a child is 1+ year old to vaccinate?
10. What is a conjugate vaccine?

Answers:
1. Blood, Lymph, Spores
2. A) Immune response to pathogen damages host B) Toxins kill cells C) Pathogen itself damages host cells by interfering with cell division or lysing cells
3. Loosely attached to blood vessel walls
4. KIRs (killer inhibitory receptors) bind and say please don't kill me
5. Cytokines affect all tissues with cytokine receptor: hypothalamus, liver, muscle and bone marrow, as well as all lymphocytes, and so induce a systemic reaction.
6. A working lymph node, where activated B cells divide and T cells recognize the antigen for which they are specific
7. Cytokines trigger B cell production of certain antibody isotypes (IL-4 → IgE, TGFbeta → IgA, IFNgamma → IgG); CD40 binding to CD40L triggers the switch to the next isotype in sequence
8. Increase shelf life (kills microbes)
9. Infants cannot mount a Th1 response until they are 12 months old and CD8s are good killers until a child is about 12 months old (breast feeding provides child with much-needed IgA until immune system can make IgG, vaccines before one year of age provoke IgE response and cause atopy)
10. A vaccine that is not immunogenic is combined with an immunogenic protein to generate protective immunity. (example: pertussis antigen in DTaP vaccine induces a strong immune response, increasing the immune exposure to, recognition and memory of diptheria and tetanus)

VACCINES
-- = inactivated or attenuated form of a pathogen → immunological memory
--herd immunity - If you protect entire population and 1 person isn’t vaccinated, that person will be protected because the herd can't get it
--what’s good for the herd, may not be good for the individual
--for extracellular pathogens (toxin/virus/bacteria before it gets in cell) B cells are most active
--for intracellular pathogens in vacuole or endosome you want CD4 (T cell) response (bacteria mostly)
--for intracellular pathogens in cytoplasm you want CD8 T cells or NKs (viruses mostly)
--antibodies (from vaccine) can neutralize toxins
--antibodies can inhibit uptake (prevent infection)
--must generate T and B cells to the correct epitopes
--with some bacteria, toxin is what's dangerous, so make a vaccine against toxin, not bact
--vaccines should generate protective, longlived immunity (not all of them do)
--booster shots used in US, but in other countries, it is harder to keep track
--vaccine should be inexpensive

MERCURY
--thimerosol is a mercury typical in vaccines: in 1999 FDA asked to remove all Hg from vaccines. Didn’t happen. There is still Hg in vaccines—but only flu. (adult tetanus?)
--10 times less than what is thought to be dangerous
--thimersol is really good deterrent for contamination and since they produce the vaccine in bulk this prevents contamination

EXCIPIENTS
--Other ingredients in vaccines: Formaldehyde, antibiotics, protein, etc.

TIMING
--hugely important in giving a vaccine
--infants who are less than 1 year old don’t get TH 1 response, can't make IFN-γ --> IgG, can't activate T cells
--when no IFN-γ (which shuts down Th2 response) if you vaccinate too early, you start a Th2 response that can not shut down --> allergic reaction develops that may be with the individual indefinitely
--Study published in March 2008 showed that delaying vaccination decreases the amount of asthma in children.
--viral vaccines: delay until after 1st birthday
--primary vaccine that is given before 1 year old is Hib, given at 2, 4, 8, and 12 months
--HiB causes bacterial meningitis in first 5 years of life
--If baby is breast fed, you get passive immunization until mom stops breast feeding

TYPES OF VACCINES
--conjugate: epitope (could be a sugar or a protein) of a pathogen is linked to a protein carrier because the epitope alone is not immunogenic, ex: Hib
--attenuated: viruses transferred to new hosts (chickens, horses, cows, etc) until they are no longer infectious for humans, ex: MMR
--killed (Heat or formalyn killed) no longer infectious --> immune response to dead virus, ex: polio, flu
--protein subunit: a single piece of a protein is used as the antigen, used if virus is too antigenic, or a protein could be toxic if the whole thing were used, ex: Hep C
--DNA, new!, use the DNA for a protein rather than the protein itself, DNA is injected intramuscularly; macrophages in the muscle make the protein, and carry it to the lymph node. Cheap but not as effective as we would like
--Peptide: theoretical: inject the peptide that would directly bind to the MHC, rather than having APCs process and present the antigen. There’s a lot of skepticism because there is no danger signal (no CD86), so you might induce tolerance. Cheaper than a subunit vaccine.
--Dendritic Cell vaccine: pull pts own monocytes, differentiate into DC's, mix with whatever you wish to kill, put back in pt, provokes big Th1 response

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