Term
|
Definition
| obsolete method of immunizing patients against smallpox by infecting them with substance from the pustules of patients with a mild form of the disease |
|
|
Term
| the first vaccine was developed by ( ) against smallpox in 1796 |
|
Definition
Jenner
inoculation with the crusts of the cowpox virus
since cowpox was also called vaccinia the technique was called a vaccination and the protective inoculum a vaccine |
|
|
Term
|
Definition
overall historically, 30% who contracted the virus died; survivors were blinded or scarred
BUT 10 million contracted it in 1967 (2 M died)
widespread vaccinations
smallpox free in 1980 (WHO)
measles and polio are also targeted for elimination |
|
|
Term
| what is the danger of smallpox in the modern world? |
|
Definition
|
|
Term
| pertussis is steadily increasing in numbers despite vaccination efforts. why? |
|
Definition
fear from vaccines maybe causing autism
paralysis fear
lack of access
don't know what vaccines they need
elderly are losing their immunity
homeschooling |
|
|
Term
| significant vaccine preventable infections |
|
Definition
influenza
pneumococcal disease
hepatitis B
pertusis |
|
|
Term
| main US diseases and pathogens with vaccines |
|
Definition
BACTERIAL:
diphtheria
tetanus
pertussis (whooping cough)
pneumococcal disease
meningococcal disease
meningitis, pneumonia
VIRAL:
influenza
hepatitis A
hepatitis B
varicella
measles
mumps
rubella
poliomyelitis
rabies |
|
|
Term
| examples of vaccines for international travel |
|
Definition
typhoid - food and water borne illness
yellow fever (liver) and Japanese encephalitis |
|
|
Term
| application of immunology to vaccine development |
|
Definition
antigens are substances that are either pathogenic (eg bacteria, viruses, protozoa) or non-pathogenic (eg vaccines) that induce an immune response that includes antibody (immunoglobulin) production
antibodies are substances produced by mature plasma cells designed to destroy a specific antigenic substance and/or to provide future exposure to the antigen
specific applications of these principles are applied to vaccines and vaccine-preventable diseases |
|
|
Term
| microbial strategies to avoid the immune system - which makes it harder for the immune system and vaccines to succeed |
|
Definition
1) mall RNA viruses use RNA polymerase which is an error prone enzyme; mutations occur frequently, and the amino acid sequence of antigenic peptides changes during infection (HIV) or between infections (influenza)
2) DNA viruses have large genomes over 50% of which may code proteins, which subvert cellular mechanisms; for example herpes viruses may down regulate MHC or prevent apoptosis
3) intracellular bacteria (mycobacteria) have waxy coats and secrete catalase to block respiratory burst
4) extracellular bacteria may have strategies for evading phagocytosis; for example the Pneumococcus has a large polysaccharide coat
5) worms (schistosomes) coat themselves in host antigens (such as MHC) to evade the immune response; they secrete protease inhibitors to block enzymes in the gut and are too large to phagocytose |
|
|
Term
|
Definition
1) naturally acquired active immunity: antigen recognition by B and T cells, co simulation leads to antibody secreting plasma cells, cytotoxic T cells, B and T memory cells
2) naturally acquired passive immunity: transfers of IgG antibodies from mother to fetus via the placenta or IgA antibodies in mother's milk
3) artificially acquired active immunity: antigens introduced during a vaccination stimulate cell mediated and antibody mediated immune response, leading to production of antibodies, cytokines, complement; antigens pretreated to be immunogenic but not pathogenic
4) artificially acquired passive immunity: intravenous injection of antibodies obtained from immune individuals; antiserum (antibody containing preparation) or antitoxin (antibodies against a toxin) |
|
|
Term
| active vs. passive immunization |
|
Definition
1) rabies immune globulin (RIG) = antibodies to help neutralize the rabies virus ASAP; prompt protection but lasts 10-12 days; PASSIVE IMMUNIZATION
2) rabies vaccine: since rabies incubates slowly; 5 dose series will protect for years; delayed but persistent defense; ACTIVE IMMUNITY
similar to hepatitis B immune globulin and vaccine |
|
|
Term
| classification scheme for vaccines |
|
Definition
LIVE
attenuated human pathogen or nonhuman pathogen or recombinant organism
ex) oral polio, measles, mumps, rubella, influenza, smallpox vaccine
KILLED
ex) pertussis, influenza
SUBUNIT:
purified peptide components or toxoids or polysaccharides or recombinant peptides or DNA vaccines
ex) acellular pertussis, diptheria, tetanus, pneumococcus, haemophilus, meningococcus, hepatitis B |
|
|
Term
|
Definition
1) live
live, but weakened
live are more effective b/c it produces stronger immunity; acts like the disease more than the killed vaccine
2) killed
3) toxoids
4) conjugated
5) nucleic acid |
|
|
Term
| live (attenuated) vaccines |
|
Definition
live vaccines were the first discovered and still most effective; most closely mimic the infection
attenuation: use the whole agent but reduce virulence; viruses (raise them for generations until lose virulence), bacteria (from mutations during long term culture or genetic manipulation)
can cause mild infections; attenuated viruses can replicate in host at the site of infection but aren't virulent; infected cells process endogenous viral antigens; trigger cell mediated immune response (helper and cytotoxic T cells), IgA antibodies
vaccinated individuals can protect those around them, providing HERD IMMUNITY
can be hazardous to immunosuppressed, pregnant people
can revert back to wild type or mutate to cause disease; example: polio epidemic in Haiti
examples of live vaccines: measles, mumps, rubella, smallpox, polio, influenza |
|
|
Term
| killed (inactivated) vaccines |
|
Definition
killed organisms are not as effective at eliciting an immune response but safer
don't replicate in the host
since they cannot replicate, booster doses needed
don't stimulate herd immunity
recognized as exogenous antigens so promotes antibody mediated immunity
2 types:
1) whole agent vaccine: deactivated whole organism; non-antigenic portions may stimulate a painful inflammatory response; ex) influenza, pertussis, rabies, polio
2) subunit vaccine: antigenic fragments of microbes; ex) pertussis, hepatitis B
when killed, must remain similar to original microbe
inactivating agents should not alter antigens responsible for stimulating protective immunity
bacteria - formaldehyde, phenols, acetone, heating
viruses - formaldehyde, ethylenimines, beta-propriolactone
since microbes of inactivated vaccines can't replicate, aren't as many antigens so antigenically weak; must use high doses or multiple doses - and/or use with adjuvants
adjuvant: a chemical added to a vaccine to increase its ability to stimulate the immune response
example adjuvants:
1) aluminum phosphate (alum): slows degradation of antigen; activates complement, stimulates macrophages
2) mineral oil, Freund's adjuvant: slows degradation, stimulates T cells (but used in animals only)
3) natural mediators: cytokins (eg IL-1, IL-12, IFN); most still experimental
may cause local inflammation or allergies |
|
|
Term
| immunostimulatory complexes (ISCOMs) as adjuvants |
|
Definition
they are able to fuse with cell membrane and deliver antigen into cell
this can elicit T cell responses |
|
|
Term
| toxoid vaccines (whole or partial) |
|
Definition
for some diseases (diphtheria and tetanus) more efficacious to induce a response to toxins than cellular antigens
toxoids: chemically or thermally modified toxins, usually made by mixing with formaldehyde; stimulate antibody-mediated response; since few antigenic determinants, reinoculations every 10 years
DTP made of diphtheria and tetanus toixoids and pertussis vaccine. two types:
1) DTwP: contains whole pertussis bacteria killed with formaldehyde; not found in US
2) DTaP: fragments of pertussis bacteria; fewer side effects |
|
|
Term
| protein vs. polysaccharide components |
|
Definition
active ingredient in most vaccines are proteins from bacteria, viruses. evoke a T cell response. ex) influenza vaccine
some vaccines work by evoking antibody response against polysaccharides (eg from bacterial capsule); ex) pneumococcal, meningococcal, Haemophilus influenzae vaccines; polysaccharide vaccines are T cell independent; polysaccharides are poor immunogens; little to no protection in young children
conjugated vaccines have been developed to deal with poor immune response in children |
|
|
Term
|
Definition
vaccines consisting of the designed polysaccharide antigen and proteins covalently bound
better response than the polysaccharide alone
ex) Hib vaccine developed around 1990. prior to this, Haemophilus influenzae b caused infant meningitis. prior to 1 years old, cannot mount an effective T independent immune response. polysaccharide antigen bound to a protein (eg tetanus toxoid) |
|
|
Term
|
Definition
B cells with immunoglobulin receptors for the baterial capsular polysaccharide part of the vaccine take up the conjugate by endocytosis
protein can be processed and presented on B cell by MHC II which is recognized by T helper cells
T helper cells activate B cells to produce antibodies against the polysaccharide |
|
|
Term
| nucleic acid (DNA) vaccines |
|
Definition
injection of naked DNA into cells can cause the production of the protein encoded in the DNA; protein persists and stimulates an immune response
DNA remains effective only until degraded
not commercially available yet
problem: delivery of antigen to intracellular pathways
solution: live viral vectors (reproduce inside host cells); DNA vaccines encode antigens inside cells; ISCOMs deliver antigens across cell membrane
problem: inadequate cytokine stimulation of the adaptive immune system
solution: toll like receptor ligands added as adjuants activate the innate immune system; pro-inflammatory cytokine genes added to DNA vaccine |
|
|
Term
| primary vs. booster reponses |
|
Definition
some vaccines are protective right after initial dose (eg influenza, pneumococcal)
others require several doses for antibodies to develop:
1) if infant (eg. DTaP)
2) if urgency (rabies)
3) if no prior exposure (pneumococcal conjugate vaccines for children)
for vaccines that require a series of doses (eg Hepatitis A, Hepatitis B, DTaP), all of the doses in the series considered primary doses necessary to ensure complete protection
booster doses are needed if antibody titers wane in time; adult boosters of Td or Tdap (tetanus) |
|
|
Term
| vaccines vs. allergen extracts |
|
Definition
vaccines cause active production of IgG antibodies
allergen extracts are made by extracting plant pollens, animal fur, or other allergen sources with extracting fluids. they are used to treat hay fever, allergic asthma, etc. these allergens induce IgE release, which causes mast cells to release histamines |
|
|
Term
| principles behind allergen extracts |
|
Definition
type I hypersensitivity (allergies): almmost all allergens are delivered to the gut or lung mucosa
stimulate T helper cells to produce cytokines that induce B cells to make IgEs that bind to mast cells in CT by capillaries; subsequent exposure binds to antigen; degranulation
vaccines: immunization with escalating doses of allergen shifts antibodies production from IgE to IgG; IgG interacts with antigen; stops allergic symptoms and IgE production (DESENSITIZATION) |
|
|
Term
| factors influencing success of vaccines |
|
Definition
population density: dense groups receive highest level of mass immunization
high vaccine coverage in infants and children
risks of infection must outweigh risks associated with vaccination
epidemiologic understanding assists design of vaccination programs |
|
|
