Seminar 9 - Vaccination (Ben) Flashcards
What is the definition of immunization?
Induction of an immune response in an organism by exposing it to an antigen
What are the 4 goals of immunization in experimental animals?
- Generation of polyclonal antibodies
- Generation of hybridomas to produce monoclonal Abs
- Induction of disease models
- Vaccine development
What often happens if a soluble antigen is injected alone?
What can be done to prevent this and induce the desired response?
- if injected alone: enzymatic antigen degradation and/or MHC presentation without co-stimulation leads to lack of an immunizing response
- adjuvants (usually some PAMP or DAMP molecule) can be added to antigen to induce co-stimulation
What generally happens if antigens are introduced orally?
- oral tolerance will develop, similar to that seen with food and flora antigens
What is a depot or carrier in terms of vaccination adjuvants?
- some way of administering adjuvant DAMP/PAMPs in a form in which they are continuously secreted over time
- these can be neutral/cationic liposomes, microspheres, ISCOMs (immune stimulating complexes)
- (ISCOMs are a mixture of cholesterol, phospholipid + saponins)
How does antigen dose affect the outcome of immunization?
(i don’t fully get the answer to this, was on slide 13 of the .ppt and i couldnt find much more info on it)
- High-dose tolerance - occurs via anergy (TCR stim. without co-stim) and deletion (via FasL/FasR apoptosis) of effector Ts by APCs
- Low-dose tolerance - occurs via Treg activation leading to effector T suppression via secreted/membrane-bound cytokines
What is the general latency time for active vaccination?
7-14 days
- between administration of vaccine + synthesis of Abs + memory cells
What are the 3 different types of whole virus vaccines?
- Live Attenuated - pathogen is altered to be less virulent
- Inactivated - pathogen is cultured + killed using heat/formaldehyde
- Live Recombinant - genome of a microbe is highly attenuated against virulence but still contains antigen genes
What are several different types of subunit vaccines?
- Purified/Recombinant Antigen - used to be taken from blood of chronically infected pt; now can be synth’d via recombinant yeast
- Toxoid - inactivated exotoxins (ex: diphth./tetanus)
- Caspsular - using capsular polysacch. (N. meningitidis/S. pneumo) or glycoprotein
How does a conjugated vaccine work?
- a less immunogenic antigen (e.g. capsular polysaccharide) is linked to a more immunogenic (e.g. toxoid) molecule to stimulate an immune response against it
- ex: H. influenzae B (HIB) vaccine consists of capsular polysacch. plus diphtheria or tetanus toxoid
What are 4 different types of Influenza A H1N1 vaccines?
- inactivated whole virus
- “split” vaccine - virus particles broken up w/ detergents
- Subunit - with hemagglutinin / neuraminidase particles
- Cold-adapted - live attenuated virus for intranasal admin.
How can serological antibody titers be used to determine the time that an infection occurred?
- Fresh Infections: will show IgM and IgG
- Chronic/Previous Infection: shows IgG only
- after first infection, some B cells undergo affinity maturation + class switching to IgG producing plasma cells; IgM producers eventually die
How do repeated “booster” doses of a vaccine enhance humoral responses in immunization?
- they induce secondary, tertiary etc. immune responses with higher levels of antibody production
- even the “baseline” Ab levels existing long after these repeated doses are higher than after the first dose
Give two examples of infections against which post-exposure passive immunization is useful.
- Rabies - within 2 days
- Hep A - within 14 days, because Hep A proliferates slowly
Via what cytokine do CD8+ T cells “self-renew” after establishment of memory cells following immunization + booster shots?
IL-2
Why must booster vaccinations be given according to a certain schedule?
- there is a minimum time between boosters because sufficient time must be given to allow establishment of memory cell populations
- too short of a time –> overreaction to first exposure; not much issue with elongating time, though
Generally, how do subcutaneous/IM vaccine injections induce immune responses?
(cell types + cytokines involved)
- DCs transport antigens to nodes+ secreteIL-12to induceTh1 differentiation
- Th1 cells secrete IFN-y and IL-2
- IgG secretion is induced + complement is activated
Considering the last card…
Subcutaneous/IM vaccinations induce protection against pathogens in what parts/fluids of the body?
(Give an example of such a pathogen)
- SC/IM injection of vaccination confers protection against pathogens in lymph and blood
- ex: Hep B
How does oral/nasal administration of vaccines induce an immune response?
(cytokines + cell types)
- M cells in mucosa transport non-processed antigens to MALT macrophages + lymphocytes
- TGF-B secretion induces Treg/Th2 responses
- B-cells are induced to secrete IgA which blocks adhesion/virulence factors + neutralizes pathogens
Pathogens in what part of the body are immunized against via oral/nasal vaccination?
An example?
- luminal/mucosal pathogens
- ex: polio
How do B cell populations differ in infants and the elderly?
- in infants: large pool of naive B cells
- in elderly: large pool of memory and plasma B cells; marrow has entered senescence + its size is limited by fat deposition
What is the difference between T-dependent and T-independent B cell activation + responses?
- T-dependent - follicular B cells activate via protein antigens and Th cells; result in long-lived plasma cells secreting high-affinity IgA, IgE and IgG
- T-independent - marginal zone/B-1 B cells activate directly via polysacch./lipid antigens; result in short-lived plasma cells + low affinity IgM
In what 3 ways can immunization of infants + the elderly be made more effective?
(What aspect of immunization does each method improve?)
- Adjuvants - activate naive B cells + incr. migration into nodes
- Higher Antigen Dose - increase B-cell activation + germinal center formation
- Boosters - migration of naive Bs to node; memory cell differentiation + survival
What is reverse vaccinology?
- an “in silico” computational form of vaccine development
- pathogen genome is screened bioinformatically + potential vaccine target genes (ex: OMPs) are cloned, expressed recombinantly + tested for immunogenicity
