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58 Cards in this Set

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Principles of vaccination
dev. immunity
recog self vs. nonself
protect from infection/disease
indicated by Ag-specific Ig
very specific
memory
what is active immunity?
protection due to person's own immune response to infectious agent
permanent but req time to dev immunity
similar to natural infection (memory) but w/o risk of disease
passive immunity
protection (vis Igs) prod in and transferred from another person or animal
rapid but temporary protection (b/c not cell-mediated)
most effective ways to prevent diease
prevent TRANSMISSION:
sanitation
control vectors (mosquitos)
prevent INFECTION:
immunization
defn: vaccines, immunization
vaccine: weak, killed whole pathogen (bacteria, virus); portion of pathogen used to stim adaptive (Ig or cell) response (active immunity)

immunization: giving vaccine (active) or Ig (passive)
EX: active natural vs. active artificial
active natural: direct exposure to infectious agent stim immune response (you get sick)

active artificial: vaccinations (intentional exposure to elicit response)
Ex: passive natural vs. passive artificial
passive natural:
transfer of maternal Ig via placenta, breast milk

passive artificial: giving purified Ig, Ig serum, or previously sensitized cells
what Ig is used to diagnose neonatal infections and why?
IgM

because neonate received IgG transplacental and secretory IgA in breast milk(protects gut)
are neonates particularly susceptible to infection after birth? if immunodef, when will it be detected?
not particularly susceptible because of maternal IgG; if are immundef, will become ill ~ 5-6 mos when maternal IgG becomes low
what type of vaccine can be particularly deleterious to neonates and why?
LIVE ATTENUATED vaccines

theres a period of time (<3mos) when we dont know if neonate is immunodef
when use passive immunity?
-pre and post exposure PROPHYLAXIS
-to REDUCE SX of ongoing disease: assist innate; neutralize, block toxins etc
-for protection in IMMUNOSUPPRESSED (because active immunization wouldnt work)
what are Ex of pre and post prophylaxis?
pre: req vaccine for travel. dont have enough time for active immunization (<2 wks); need rapid, transient immunity

post: we know someone who is contagious has been exposed to others; given to exposed; short-lived (1 wk)

ex: Hep A, Measles
sources of passive immunity?
Sera from blood donors- general, non-specific Ig; prov protection against major pathogens
Plasma from seropositive ppl (high Ig titers)- protection against SPECIFIC pathogens; hyperimmune
Monoclonal Ig- high affinity, neutralizing Ig from culture
Heterologous hyperimmune serum- antitoxin from animal
What are the risks to patients? (4)
1. allergic, anaphylactic rxns (type 1 HSR)- contaminant in vaccine
2. serum sickness (type 3 HSR)- react to Ag determinants on Ig from nonhuman source
3. tramit blood borne pathogens- contaminated donors
4. immunosuppresion- Ig blocks Ag and prevents active adaptive response from developing
Active immunization charac (6)
-immunogenicity: humoral and cell-mediated
sometimes cant activate both
-block adherence; prevent colonization
-neutralize toxins
-promote opsonization/phagocytosis
-promote TH1 (to activate CD8-->CTLs)
-induce memory
what components of vaccines (antigenic target) will induce humoral vs. cell mediated immunity?
humoral- toxins, surface Ag

cell mediated- any microbial component; must be capable of being processed, presented by APCs to T cells (esp MHC I to CTLs)
types of vaccines in active (artificial)immunization
inactivated, whole cell: (safe); can have side effects to components (G- LPS)
live attenutated
toxoid- nontoxic, but will stim prod of protective Ig
subunits-mbr, capsule protein, cell-free extract of secretion that is virulence factor
DNA vaccines: inject DNA for antigenic portion of microbial protein; host cells take up DNA and prod microbe protein (HIV vaccine?)
what is an attenuated vaccine?
mutant form of the wild type (isolated in population);
lacks deleterious components that would allow replication;
maintain immunogenic components;
usually grown in culture, animals
charac of inactivated vaccines
CANNOT REPLICATE
formalin, heat used
whole bacteria or viruses
when are inactivated vaccines used?
with microbes that cant be attenuated
microbes with oncogenic potential (if has potential to integrate, transform)
disadvantages of inactivated vaccines?
not as effective as live
no lifelong immunity
req lger doses, more doses/boosters
primarily humoral resp (no CTLs if microbe not processed, presented)
only serum Ig (no secretory)
titer decr with time, boosters
anaphylaxis
ex of inactivated vaccines
viral:
polio, influenza, rabies, Hep A

bacterial:
pertussis, typhoid, cholera, plague
what is a key concept with inactivated vaccines?
need to retain antigenicity in order to prod Ig resp and develop immunity
dont want to just kill the vaccine components before stim immune response
describe the cholera vaccine
problem with cholera is the toxin (AB toxin)
vaccine contains recombinant protein for the B subunit only
stim Ig resp against the B subunit
will provide immunity (prevents adherence) without chance of A subunit entering
charac of live attenutated vaccine
most likely to mimc natural infectoin
MUST BE ABLE TO REPLICATE
use mutant or attenuated strains
-weak wild type strain
genetically engineered strains-remove virulence; retain antigenicity
when do you use live attenutated vaccines?
when you require a T cell response (CTLs) or a secretory IgA (mucosal protection; intranasal)
advantages of live attenuated?
immune response generated mimics natural infection
only req low dose, 1 time
CELLULAR and humoral responses
disadvantages to live attenuated vaccine?
possible severe rxns
dangerous for immunosuppressed, pregnant
can revert to virulent form
vaccine is fragile to store
what is the name of the Tb vaccine and why dont we use it in the US?
BCG vaccine
not used in US because we use PPDs to test for exposure to Tb. if had vaccine, would give a positive PPD
what is the route of administration for killed whole vs. live attenuated vaccines?
killed whole- IM
live attenuated- intranasal, oral if req mucosal immunity
what is the only way we can provide mucosal immunity by stimulating secretory IgA?
live attenuated vaccines
oral, duodenal protection
what are subunit vaccines?
composed of isolated microorg structures or toxins that have antigenicity to stimulate protective Ig response
why do we use subunit vaccines?
many components of microorg can elicit adverse side effects and yet not be immunigenic (ex:LPS)
we can remove these or isolate other components to reduce side effects
what is a recombinant Ag vaccine? ex?
we know a certain sAg (surface Ag) stim prod of protective Igs;
clone the gene for the sAg; recombination tech to insert into yeast cell; yeast cell makes sAg; purify product for vaccine
ex: Hep B vaccine
what are some charac of recombinant Ag vaccines?
can choose Ag that doesnt vary b/w strains (ex: HBsAG)

Ag self assembles into Virus Like Particle (VLPs) (but has no genome)
what is an ex of a microorg with diff serotypes but for which we can make recombinant Ag vaccine.
Recombinant HPV
cant make one strain for all vaccines
still has some self-assembly
ex: 6,11- cervical
16,18- oncogenic forms
preparation of subunit?
formalin, heat inactivated protein or toxin
purify, syn subunits
when do we use subunit, fractional vaccines?
when microbes cant be attenuated;
when colonization doesnt lead to disease; organism removed before stimulates immune response
ex of recombinant Ag vaccines?
Recombinant Subunit (HBV)
polysaccharide, peptide (Hib, Anthrax)- T-independent; only stim low affinity IgM
conjugate (Hib, pneumococcal)
disadvantages of subunit vaccines
no lifelong immunity; req boosters, large doses
only humoral resp
anaphylaxis
(~inactivated)
what is the anthrax vaccine?
subunit vaccine against PA (binding) portion
what are 2 examples of vaccines against toxoids?
diptheria, tetanus
charac of pure polysaccharide vaccines
not always immunogenic (<2yo)
T-independent-->less fxnal Ig
(no class switch, memory)
no memory-->no booster response
how can we improve the immunogenicity of polysaccharide vaccines?
conjugation of polysaccharide to an immunogenic protein (ex:toxoid)
allows complex to be processed, presented-->T cell help
ex of pure polysaccharide vaccines?
many made to capsule components;
pneumococcal- polyvalent; 23 capsular types
good for >65yo
ex of conjugated polysaccharide vaccine?
important for infants
pneumococcal- heptavalent; conjugated to diphtheria toxin CRM197
what is original antigenic sin? how does it explain hesitation to use avian vaccine?
tendency of immune system to use memory
primary infection results in memory B cells with Ag specific Ig
Antigenic drift tends to occur, esp in viruses
altered virus may still activate memory cell
memory response faster than primary resp to new epitopes->no new Ig being made to altered virus
memory Ig may not bind as effectively->LESS EFFECTIVE IMMUNE RESPONSE
whats the difference between recombinant Ag and recombinant vector vaccines?
recombinant Ag- antigenic gene inserted into yeast cell and protein prod in culture for vaccine
recombinant vector- insert antigenic gene into an organism that will injected and replicate to prod protein inside host
what is reverse vaccinology?
because we have the genome sequence for many microbes, reverse vacc allows us to develop vaccines from relevant Antigenic epitopes FASTER by ID areas of the genome that are antigenic.
how are virosomes, iscoms and synthetic peptides used for vaccines?
virosomes- proteins that dont self assemble

iscoms- cagelike complex of cholesterol, immunogen, lipid

syn peptides- when we know antigenic epitope so syn peptide region of that epitope
how are B and T cell epitopes used in syn peptide vaccines?
B cell epitope- aa seq that will elicit Ig of a certain specificity
T cell epitope- aa seq that can bind MHCII motifs
B cell epitope is non-immunogenic w/o the T cell epitope because req presentation by MHCII to T cells to elicit specific Ig production by B cells
what is an advantage and a disadvantage of the B/T cell epitopes in syn peptide vaccines?
advantage- since we have defined MHC binding motifs we can scan for aa seq in Ag proteins that will bind a particular MHC

disadvantage- req prod of many T cell epitopes since each will be MHC-specific (ie. one T cell epitope wont fit all MHC)
how to make flu vaccine?
combine HA and NA from strain 1 with six other genes from strain 2 which grows well in eggs and is harmless to humans;
remove virulent portion of HA, Ha and NA are spliced into plasmids. each of the six other genes are also spliced into plasmids; all the plasmids are added to animal tissue culture; animal cells produce desired NEW flu strain. (NOT A RECOMBINANT)
what are vaccine adjuvants?
agents that modify the effect of other agents while having few if any effects when given by themselves;
increase immunogenicity in a NONSPECIFIC way
produce stronger more effective resp the vaccination
ex; Alum (aluminum sulfate)
why are adjuvants becoming more important in vaccines?
adjuvants are required when we aren't using the whole microbe to develop the vaccine. when we start using only microbial proteins etc. it makes the vaccine safer but also reduces its overall antigenicity and efficacy.
more ex. of adjuvants
LPS-derived MPL (monophosphoryl Lipid A): activates TLR4
CpG oligonucleotides: activate TLR 9
what are some new delivery methods for adjuvants?
recombinant vectors-deliver gene
virosomes
DNA plasmids-deliver gene
how are virosomes used to deliver adjuvants?
a vesible with a unilamellar pospholipid bilayer;
usually represent empty influenza envelopes
can add adjuvant into mbr