Immuno 18: Vaccines

Question 1

What is a vaccine, really?

Answer 1

Vaccination is the deliberate administration of either killed or living forms of a pathogen, or antigens derived from that pathogen in an effort to elicit an immune response that will prevent infection upon exposure to that pathogen.

Question 2

What was the most effective vaccine ever made?*

*probably not high yield, but could make you look smart on your rotations.

Answer 2

Smallpox vaccine. (also happened to be the first formulated)

Question 3

What is the goal (immediate, on a molecular scale) of giving someone a live, attenuated virus vaccine?
Describe this in terms of what MHC complex will be used and what effector cells will be activated.

Answer 3

To deliver the immunogens of the pathogen to the MHC class I pathway with the goal of activating a CD8+ T cell effector response.

Question 4

With vaccines that are either killed, subunit, or conjugated capsular vaccines, the goal is to deliver the immunogen(s) into the MHC class ___ pathway, with the aim of eliciting a potent ___ cell response against the pathogen.

Answer 4

MHC class II; B cell

Question 5

Activating B cells with killed, subunit, or conjugated capsular vaccines will elicit a cell-mediated or humoral response?

Answer 5

Humoral, via activating B cells via MHC class II

Question 6

Describe what is meant by a virus needing to be “safe” to be considered effective.

Answer 6

Vaccine must not itself cause morbidity or mortality.

Question 7

Describe what is meant by a virus needing to be “protective” to be considered effective.

Answer 7

Vaccine must protect against illness resulting from exposure to live pathogen.

Question 8

Describe what is meant by a virus needing to “grant sustained protection” to be considered effective.

Answer 8

Protection against illness must last for several years.

Question 9

Describe what is meant by a virus needing to “induce neutralizing antibodies” to be considered effective.

Answer 9

Some pathogens (such as polio virus) infect cells that cannot be replaced (e.g. neurons). Neutralizing Ab is essential to prevent infection of such cells.

Question 10

Describe what is meant by a virus needing to “induce protective T cells” to be considered effective.

Answer 10

Some pathogens, particularly intracellular, are more effectively dealt with by cell-mediated responses.

Question 11

Describe “practical considerations” needed for a virus to be considered effective.

Answer 11

Low cost per dose
biological stability (e.g. if no freezer for storage, etc.)
Ease of administration (no needle, better received by pts)
Few side effects

Question 12

Why does the amount and route of exposure of a vaccine present a challenge to those designing vaccines?

Answer 12

Immune system is designed to respond to physiological amounts of antigen/immunogen.
Route of vaccination needs to match the normal route of infection for maximum benefit.
Immune system tailors immune responses depending on whether the pathogen likes to live intracellularly (Th1 response = CTLs) or extracellularly (Th2 response = Abs)

Question 13

T/F: Given a primary (1st time administered) administration: the Ab response by the body is positively correlated with the antigen dose administered in a vaccine. Meaning: increasing Ab response for increasing dose (concentration) of immunogen.

Answer 13

False. More complicated than simply a positive or negative correlation.
Given a primary administration:
A threshold amount of antigen had to be administered before any real immune response was elicited. As the dose of the immunogen increased, the immune response increased too, until really high doses were administered, at which point the response to the vaccination actually begins to drop.

Question 14

Describe the immunological response to a low dose administered following a very low primary dose administration. (Low zone tolerance)

Answer 14

Because the immune system is designed to not respond to very low concentrations of antigens, when really low doses of antigens are administered following immunization, any responding lymphocytes are subject to being removed from the repertoire.

Question 15

Describe the immune response to a medium secondary dose administered following a medium primary dose administration.

Answer 15

This elicits the ideal immune response.

Question 16

Describe the immune response to when a primary dose is very high and the secondary dose is medium. (High zone tolerance)

Answer 16

Those that received very high primary doses respond very poorly to the booster. This indicates that the immune system is designed to tolerize itself against any antigen that is supplied in amounts that are too high to be physiological for an infection.

Question 17

Describe the route of immunization trade-off for parenteral (via a needle) immunization.

Answer 17

Promotes strong systemic responses, but cannot prime mucosal responses. The systemic and mucosal immune systems are compartmentalized so that parenteral immunization will not elicit mucosal response, but immunization via a mucosal route can elicit both mucosal and systemic responses.

Question 18

In a word, describe the mucosal immune response to vaccines administered IV, sub-Q, or IM (parenteral).

Answer 18

Poor.

Question 19

In 4 words, describe the systemic immune response to parenteral vaccines.

Answer 19

Strong. Like great oxen.

Question 20

Describe the mucosal and systemic immune responses to vaccines administered via the mucosal route.

Answer 20

Both strong. Like proud mountain goat. (don’t ever face off with a mountain goat, he will destroy you)

Question 21

Has effective vaccination via the mucosal route been simple or difficult to date?

Answer 21

Difficult

Question 22

When an antigen (or a vaccine immunogen) is taken up by APCs from the extracellular mileau, peptides derived from that antigen (or immunogen) are presented primarily on MHC class II molecules and are presented only to _____ T cells.

Answer 22

CD4+ T cells

Question 23

When an APC presents a peptide from an antigen (or vaccine) to CD4+ T cell via an MHC class II molecule, because of the cytokines that are produced by the APC, these CD4+ T cells will tend to differentiate from Th0 to ____ cells following activation adn proliferation, and the end result will be a _________ (pick: antibody or cell-mediated) immune response to the pathogen.

Answer 23

Th2 cells; antibody response

Question 24

If the pathogen was an intracellular bug (or live attenuated intracellular vaccine), peptides derived from its antigens or immunogens will be most efficiently presented via the MHC class ____ pathway and will be presented primarily to ____ T cells.

Answer 24

MHC class I pathway; CD8+ T cells

Question 25

Presentation of peptide determinants via MHC class I pathway to CD8+ cells will typically result in priming of CTL responses and differentiation of proliferating CD4 Th0 cells into ____ cells.

Answer 25

Th1

Question 26

Describe the tolerance mechanisms of the immune system that a vaccine must be able to bypass to be effective.

Answer 26

Must supply appropriate “danger” signals that can be recognized by PRRs on phagocytes so that APCs will express the co-stimulatory (B7) on their surface.

Question 27

What happens to a naive T cell that receives the primary signal of activation from an APC but no secondary (B7) signal?

Answer 27

It becomes anergic

Question 28

What happens if B7 on an APC binds to CD28 on a naive T cell in the absence of peptide recognition via MHC?

Answer 28

Nothing.

Question 29

What happens if the APC expresses B7 on its surface when the T cell recognizes its cognate peptide bound to an MHC molecule?

Answer 29

The T cell will become activated, will begin to proliferate, and the daughter cells will differentiate into either effector T cells or memory T cells.

Question 30

List the two broad classifications for vaccines:

Answer 30

1) Whole pathogen vaccines- either live attenuated or whole but killed.
2) Subunit vaccines- purified components or mixtures of pathogen-derived antigens. Can be recombinant forms of pathogen components, or they can be genetically engineered into delivery vector organisms that express components of a pathogen but not too much pathogenicity.

Question 31

What is an adjuvant?

Answer 31

A material that is used to enhance the adaptive immune response that will be made to a vaccine immunogen. Usually, the adjuvant must be co-administered with the vaccine immunogen to be effective.

Question 32

What is an adjuvant that is considered a depot?

Answer 32

It allows for slow, timed (delayed) release of the antigen.

Question 33

Why is Freund’s adjuvants not approved for use in humans?

Answer 33

Too many side effects

Question 34

Where are Freund’s adjuvants used?

Answer 34

Research

Question 35

Describe Alum adjuvant, what MHC complex it delivers antigen to, and its efficacy.

Answer 35

AlOH gel that immunogens can be complexed with. Also a depot former. Delivers antigen to MHC class II Not terribly effective. Works best in combination with B. pertussis PAMPs which promote co-stimulator expression.

Question 36

Describe MF59 adjuvant and what MHC complex it delivers antigen to.

Answer 36

Depot former that is a squalene, oil, and water emulsion. Delivers immunogen to MHC class II.

Question 37

What are immune stimulatory complex (ISCOMs) adjuvants and what MHC complex do they deliver immunogens to?

Answer 37

matrix of lipid micelles that can be loaded with the immunogen of choice. Micelles fuse with the cytoplasmic membrane of host cells, including APCs, dumping the immunogen into the cytoplasm of the cell. Therefore, ISCOMs are used for delivery of immunogens into the MHC class I processing and presentation pathway.

Question 38

What is a liposome?

Answer 38

A highly stable closed vesicle formed by a single bilayer of phospholipids.

Question 39

What is the difference between a micelle and a liposome?

Answer 39

Liposome has a bilayer of lipid. Micelle is a single layer with hydrophilic heads as cortex and hydrophobic tails as core.

Question 40

Why are some bacterial toxins useful as mucosal adjuvants?

Answer 40

High potential for promoting immune responses to immunogens that are delivered via the mucosal route.

Question 41

What is the problem with bacterial toxin adjuvants?

Answer 41

They are still toxic. Their toxicity and adjuvanticity may be dependent on one another.

Question 42

What are the advantages to using live attenuated viruses as vaccines?

Answer 42

They replicate within the proper body compartment or infect the appropriate cells and replicate within them, generating physiologically appropriate amounts of antigen. They also deliver their antigens to the appropriate processing and presentation pathway, and they elicit appropriate cytokine/chemokine signalling that ultimately promotes the right type of immune response to deal with that particular pathogen.

Question 43

How are viruses attenuated in-vitro so they are not pathogenic in humans?

Answer 43

First grown in human cells.
Virus transferred to monkey cells, where it acquires mutations that allow it to grow well in monkey cells, but make it not able to grow well in human cells.
Now the virus is attenuated and can be used to immunize pts.

Question 44

What is a possible complication of live attenuated vaccination that can lead to iatrogenic disease (disease caused by medical treatment)?

Answer 44

Reversion of the virus to virulent form

Question 45

How are viruses attenuated using recombination DNA techniques and why is this safer than in-vitro methods such as the monkey-torture method (jk I know what in-vitro means)?

Answer 45

Recombination DNA techniques either mutate or excise one of more virulence genes from the genome of the pathogen. Once the gene(s) are either mutated or removed, it is very difficult for the virus to revert to its highly pathogenic, wild-type form.

Question 46

What is a problem with the DNA recombination attenuation technique?

Answer 46

Difficult to identify one or more virulence genes, that when mutated, cause attenuating of the pathogen without dramatically altering its infectivity and/or its replicative capacity.