Seminar 9 - Vaccination (Ben) Flashcards

1
Q

What is the definition of immunization?

A

Induction of an immune response in an organism by exposing it to an antigen

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2
Q

What are the 4 goals of immunization in experimental animals?

A
  1. Generation of polyclonal antibodies
  2. Generation of hybridomas to produce monoclonal Abs
  3. Induction of disease models
  4. Vaccine development
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3
Q

What often happens if a soluble antigen is injected alone?

What can be done to prevent this and induce the desired response?

A
  • 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
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4
Q

What generally happens if antigens are introduced orally?

A
  • oral tolerance will develop, similar to that seen with food and flora antigens
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5
Q

What is a depot or carrier in terms of vaccination adjuvants?

A
  • 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)
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6
Q

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)

A
  • 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
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8
Q

What is the general latency time for active vaccination?

A

7-14 days

  • between administration of vaccine + synthesis of Abs + memory cells
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9
Q

What are the 3 different types of whole virus vaccines?

A
  1. Live Attenuated - pathogen is altered to be less virulent
  2. Inactivated - pathogen is cultured + killed using heat/formaldehyde
  3. Live Recombinant - genome of a microbe is highly attenuated against virulence but still contains antigen genes
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10
Q

What are several different types of subunit vaccines?

A
  • 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
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11
Q

How does a conjugated vaccine work?

A
  • 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
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12
Q

What are 4 different types of Influenza A H1N1 vaccines?

A
  1. inactivated whole virus
  2. “split” vaccine - virus particles broken up w/ detergents
  3. Subunit - with hemagglutinin / neuraminidase particles
  4. Cold-adapted - live attenuated virus for intranasal admin.
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13
Q

How can serological antibody titers be used to determine the time that an infection occurred?

A
  • 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
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14
Q

How do repeated “booster” doses of a vaccine enhance humoral responses in immunization?

A
  • 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
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15
Q

Give two examples of infections against which post-exposure passive immunization is useful.

A
  • Rabies - within 2 days
  • Hep A - within 14 days, because Hep A proliferates slowly
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16
Q

Via what cytokine do CD8+ T cells “self-renew” after establishment of memory cells following immunization + booster shots?

A

IL-2

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17
Q

Why must booster vaccinations be given according to a certain schedule?

A
  • 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
18
Q

Generally, how do subcutaneous/IM vaccine injections induce immune responses?

(cell types + cytokines involved)

A
  • DCs transport antigens to nodes+ secreteIL-12to induceTh1 differentiation
  • Th1 cells secrete IFN-y and IL-2
  • IgG secretion is induced + complement is activated
19
Q

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)

A
  • SC/IM injection of vaccination confers protection against pathogens in lymph and blood
  • ex: Hep B
20
Q

How does oral/nasal administration of vaccines induce an immune response?

(cytokines + cell types)

A
  • 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
21
Q

Pathogens in what part of the body are immunized against via oral/nasal vaccination?

An example?

A
  • luminal/mucosal pathogens
  • ex: polio
22
Q

How do B cell populations differ in infants and the elderly?

A
  • 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
23
Q

What is the difference between T-dependent and T-independent B cell activation + responses?

A
  • 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
24
Q

In what 3 ways can immunization of infants + the elderly be made more effective?

(What aspect of immunization does each method improve?)

A
  1. Adjuvants - activate naive B cells + incr. migration into nodes
  2. Higher Antigen Dose - increase B-cell activation + germinal center formation
  3. Boosters - migration of naive Bs to node; memory cell differentiation + survival
25
Q

What is reverse vaccinology?

A
  • 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
26
Q

What is an “immunodominant epitope”?

A
  • an antigen has many epitopes which “compete” for presentation by MHC, based on their affinity for binding its peptide groove
  • the epitope with highest affinity (and thus most-commonly presented) is the immunodominant epitope
  • this dominant peptide should be used as the injected molecule in subunit vaccines
27
Q

Describe dendritic cell “vaccination”.

A
  • in prostate cancer patients, blood/marrow plus cancer cells are removed
  • monocytes are isolated from blood/marrow + stimulated to diff. into dendritic cells
  • DCs are cultured with tumor cells, prostate antigens (prostate acid phosphatase) + GM-CSF ex vivo to incr. their tumor peptide presenting ability
  • mature DCs then injected back into patient to fight tumor cells in vivo