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IMMUNOLOGY: CMOD-Block 2 > (19) Vaccination > Flashcards

(19) Vaccination Flashcards

1
Q

What is Variolation?

- what disease was this used for?

A

Variolation - dried pustules of people with small pox were collected and used to scratch the skin of unaffected individuals in order to evoke an immune response

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2
Q

How was the 1st smallpox vaccine formulated?

A
  • Cowpox has similar surface determinants as the small pox virus
  • Exposure to cowpox elicits Neutralizing Abs. that are can also be used for small pox
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3
Q

What was the morbidity rate of smallpox?

A

25% of people infected died

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4
Q

What is the major difference in how your immune system responds to a live attenuated virus vs. a killed virus?
- why is this the case?

A

Live Attenuated:

  • Triggers an MHC class I response
  • This is because the virus actually infects the cell a produces proteins inside that can be imported and present via TAP-1/2

Killed:

  • Triggers an MHC class II response
  • Only APCs can take this up and present it
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5
Q

What immunological effects (as far as cells provoked) must be considered when designing a vaccine?

A

You must consider if neutralization or if T cell mediated responses are more important

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6
Q

Why is polio best prevented by a vaccine elicits a primarily humoral response?

A

Polio infects neurons which express very little MHC class I, and no MHC class II (obviously) so its important to make sure the virus never gets to the neuron or its chances of getting detected by T cell mediated immunity is slim

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7
Q

On first administration of a vaccine, what happens when the level of injected vaccine get too high?

A

Immunogenicity of the Vaccine actually Decreases

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8
Q

On second administration with a constant amount of vaccine to a group that had originally been given the following vaccine doses, what do you expect to see for:

  • Really low doses
  • Low doses
  • Medium doses
  • High doses
A

Really Low Doses:
- The body actually responds by KILLING T-cells that were differentiated to react the the virus the first time

Low Doses:
- Very little Response seen

Medium Doses:
- The cell population that was differentiated off of the first administration increases to very high levels

High Doses:
- Responding cells are killed because the body know that there is too much antigen around for this to be an infection

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9
Q

T or F: for a vaccine to be most effective it must be injected

A

False, the most effective method to administer is the one that most closely resembles the original route of infection

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10
Q

What is the problem with giving vaccines for diseases such as the flu parenterally (IV, IM, Sub-Q)?
- what about giving it via mucosal route?

A
  • Mucosal Antibodies for the virus are not created this way
  • In contrast if the vaccine is given in the mucosal route then it covers for BOTH Mucosal infection AND Systemic infection
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11
Q

If you must give a vaccine via Parenteral administration, methods of parenteral administration will you want to try first, second, third, and last?

A

Subcutaneous > Intraperitoneal > Intramuscular > Intravenous

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12
Q

What immune Response is typically primed by live attenuated viruses?

  • MHC type?
  • cell type?
A
  • MHC class I presents to CD8 cells
  • TH0 is pushed to TH1 cells

**Note the same goes for an intracellular bacteria

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13
Q

What T cell is is favored in response to extracellular pathogens?

A

TH2 - vaccines that remain extracellular will push the response to this type

  • Drives ANTIBODY production (IgA, IgE, IgG2, IgG4)
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14
Q

What is the problem with administering a vaccine that does not evoke “danger” signals?

A
  • No danger signals = no B7 upregulation via the PRRs and APCs
  • Additionally cells that bind T cells that bind MHC when do B7 is present become anergic and die

**Without B7 no immune response can be generated no T cell activation => no B cell activation => 0 response

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15
Q

T or F: while a vaccine may elicit an immune response, that immune response may not be protective

A

True, this is a waste of energy and cell space to mount a response to antigens that are not representative of what is seen on the bug

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16
Q

What is a whole pathogen vaccine?

- example?

A
  • Whole Wild-Type bug can be used (cowpox for small pox)
  • Attenuated bug can be used

**Polio Vaccine is the prime example of using the whole thing

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17
Q

What is a subunit vaccine?

A
  • Purified components
  • Mixtures of Pathogen-Derived Antigens
  • Can be recombinant forms of pathogen components or engineered into delivery vector organisms
18
Q

Which is better whole pathogen or subunit vaccines?

A

Different Formats depend on what type of Response is needed

19
Q

What is an adjuvant?

A

Material that MUST be co-administered with the vaccine to ELICIT an IMMUNE RESPONSE so that B7 can be upregulated and the vaccine can be effective

20
Q

What are common features of all of the Freund’s Adjuvants?

  • what are they made of?
  • how are they typically administered?
  • are these used in humans?
A

**When mixed with antigen these form a paste like substance that releases antigen slowly over a couple of weeks

Made of:
Oil and Water Emulsion

Administered:
Subcutaneously

NOT used in Humans - too many side effects

21
Q

Compare Freund’s incomplete adjuvant to the complete and MDP adjuvants.

A

Complete and MDP adjuvants include Mycobacterial PAMPs that can be recognized by APCs and cause B7 upregulation

22
Q 
What adjuvants are used to push antigen presentation mostly to the MHC class II pathway? 
- what is another common feature of these adjuvants?
A

Freund’s Adjuvant
Alum
MF59

***these all form Depots allowing for slow release from the site of injection

23
Q

What is Alum?

Alum is not terribly effective, so it is often paired with what to make it more effective?

A

Alum - Aluminum Hydroxide Gel

Alum can be paired with Bordetella pertussis to bind to PAMPs and promote co-stimulation needed to activate T cells

24
Q

Suppose you want your vaccine components to get presented on MHC class I. What Adjuvant should you use and why?

A

ISCOMs (immune stimulatory complexes) are your best bet because they are MICELLES that FUSE with the cytoplasmic membrane of cell INCLUDING APCs

**This allows for presentation via the MHC class I pathway

25
Q

What are some good bacterial toxins that can be used ad adjuvants?
- what is the main drawback?

A

Toxins:

  • Cholera Toxin
  • E. Coli Heat-Labile Toxin
  • Pertussis Toxin

Drawback:
- These molecules are inherently toxic, we need a way to separate adjuvanticity from toxicity

26
Q

Why are attenuated vaccines almost always more effective than killed vaccines?

A
  1. The Replicate in the Host and Generate the Appropriate amount of antigen
  2. Antigen is delivered into the appropriate cell compartment
  3. Appropriate cytokine/chemokine signaling is produced to steer immune response
27
Q

What is the main concern with attenuated vaccines?

A

Iatrogenic Disease b/c of Reversion back to Virulent form

28
Q

What is the monkey method of viral attenuation?

- Main issue?

A
  • Virus is inserted into monkey cells and allowed to replicate over and over (cultured)
  • Virus can then infect human cells but they are now much less effective at causing disease

**Virus can very easily gain its virulence and be spread to Niave individuals (note: it will most likely not cause disease in the person who received the vaccine)

29
Q

What is the Recombinant method of Viral attenuation?

  • difficulties?
  • Relative safety?
A
  • Virulent genes are removed from the genome using recombinant Techniques

Difficulty:
- Removal of Virulence genes may result in the virus not eliciting an immune response

***This is a much safer way to do things than the monkey method.

30
Q

What disease symptoms are caused by the Rotavirus?

A
  • Severe Childhood Diarrhea
31
Q

In what ways is Rotavirus very similar to the flu virus?

A
  1. Immune protection is rendered via Envelope Glycoprotein-specific NEUTRALIZING abs.
  2. High Mutation rates of Envelope Glycoproteins VP4 and VP7 gives rised to Immunologically distinct serotypes
  3. Segemented genome (11 dsRNAs) can be exchanged in a superinfected cells
32
Q

What properties of Rotavirus allow it to undergo antigenic drift and antigenic shift?

A

Antigenic Drift - via the High mutation rate of VP4 and VP7

Antigenic Shift - via 11dsRNAs that can be exchanged if a single cell is infected by more than one version of the virus

33
Q

What vaccine types are Rotarix and RotaTeq?

- what are their defining features?

A

Both are Attenuated Rotaviruses

Rotarix:
- expresses the two most important variants of VP4 P8 and VP7 G1

RotaTeq:
5 different Rotavirus Strains used
- these are genetically engineered to express common human variants of VP4 and VP7

34
Q

How many serotypes of rotavirus are there?

- how many are responsible for disease?

A

42 serotypes

*only 5 are responsible for disease

35
Q

T or F: a Adjuvant is needed with live attenuated viruses

A

False, these viruses are alive and so should elicit their own immune response

36
Q

Suppose you purify a polysaccharide and use it as a vaccine. What will be the immune response to this?

A

You will only get a T-independent response form B1B cells and only IgM will be made. The biggest problem however, is that NO MEMORY Response is generated

37
Q

T or F: since all viruses are intracellular, all vaccines should be created to generate a CD8 response.

A

False, just because something is intracellular (whether it be a bacteria or a virus) it doesn’t mean that CD8 cells are most important in fighting it (e.g. Mycobacterium infections, and the Flu)

38
Q

What happens if you give a killed bug with no adjuvant?

A

It just gets flushed through your system.

39
Q

What key response should you try to evoke for an encapsulated bacterium?

A

Complement so you need to make an IgG response

40
Q

Why for a TB virus would it be more advantageous to use an attenuated strain than to use a whole killed vaccine?

A

Goal is to initiate the TH1 response

Live = Macrophage Gets infected:

  • B7 will get up-regulated
  • Intracellular raises conc. pushing TH1 response
  • Macrophages get infected - Presumably this leads them to secrete IL-12 which pushes TH1 differentiation
41
Q

Vaccines delivered via ISCOMs will be presented on what?

A

MHC class I

IMMUNOLOGY: CMOD-Block 2 (10 decks)

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