Lecture 20 Vaccines Flashcards

1
Q

What happens during the primary exposure to an Ag?

A

Ag is processed and presented to helper T cells which is a time consuming process.

IgM predominant form in humeral response.

There is a delay before more specific (affinity maturated) and versatile IgG are produced.

A large amount of effector cells are produced, and less memory cells are produced.

After clearance, the primary immune response is rapidly down regulated and effector cells cleared.

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2
Q

What happens during the secondary exposure to the same Ag?

A

Memory cells (which match the antigen to a great specificity) initiate a rapid response.

IgG predominates.

The secondary immune response lasts longer. It is more severe, suppresses another primary response.

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3
Q

Why does a secondary response suppress a primary response to the same pathogen?

A

If the body already has highly specific Ig with a high affinity for the antigen, then it is a waste of the body’s energy to send more naive B cells through the same affinity maturation process.

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4
Q

Detail the difference between IgM and IgG in a primary and secondary adaptive immune response.

A

IgM have lower affinity, and are present more in the primary adaptive response.

IgG have higher affinity, and are produced by B cells that have undergone affinity maturation. These are slowly produced in a primary response but are quickly produced and predominate in a secondary response after antigens bind memory B cells. These memory B cells also act to inhibit differentiation of naive B cells limiting the amount of IgM made.

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5
Q

What happens to the affinity of IgG after successive exposure to an antigen or immunogen and why?

A

With each successive exposure to the same antigen, memory B cells are activated to undergo successive rounds of proliferation (affinity maturation). In these rounds there is selection for receptors that bind the antigen the best. Thus antibody affinity increases with each successive exposure.

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6
Q

What is the difference between active and passive immunization?

A

Active immunization stimulates an immune response using an antigen and creates immunological memory. The antigen can be naturally or artificially acquired.

Passive immunization involves introduction of Aby or cells produced by another individual / animal. Transfer of antibodies such as from mother to fetus or newborn through milk does not create immunological memory.

Passive immunization through transfer of cells or tissues can lead to residual immunological memory in the sense that these donated cells will continue to produce antibodies / immunity as long as they exist / survive. This can also lead to graft - vs - host disease.

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7
Q

What is the difference between killed and attenuated pathogens in terms of vaccine development?

A

Some pathogens are killed or inactivated by use of chemicals, heat, or irradiation such as influenza, rabies, polio.

Other pathogens are attenuated where they they lose their pathogenicity in humans but are still alive.

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8
Q

What are some ways inactivated vaccines are made?

A

Inactivated vaccines can use chemical (formaldehyde), heat, radiation to kill or inactivate the the pathogen.
These pathogens can also be killed and fractionated according to their cellular contents to produce an immunogenic fraction.
Vaccines can also be made by using anti-idiotype antibodies.

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9
Q

What are the pros and cons of inactivated vaccines?

A

These are safer as they cannot reacquire virulence and are not intact.

These require repeated administration, higher doses, and do not induce an inefficient immune response as the antigenic surfaces are often denatured.

There is no induction of cytotoxic leukocytes as whole as pathogenicity and infection of cells is necessary for this.

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10
Q

What are some ways live attenuated vaccines are made?

A

Chemical, heat, radiation
Non-pathogenic mutant
Related non-pathogenic species with conserved epitopes.
Recombinant live vaccines remove virulence.

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11
Q

What are the pros and cons of live vaccines?

A

These cause a specific and relevant immune response as intact cells are used with non-denatured epitopes.
Smaller doses are required. There is a longer memory of the pathogen
Cytotoxic leukocytes are induced in response to these live but attenuated viruses.

However, there is a risk of reversion to a pathogenic form. This type is contraindicated for the immunocompromised.

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12
Q

How are attenuated pathogenic viruses made by mutation?

A

Pathogenic viruses are isolated from a patient and grown in human cells.

These viruses are cultures in monkey cells to cross react them with a similar species.

As the viruses react with the monkey cells they acquire mutations that favour pathogenicity in monkey cells.

These mutated viruses are grown in human cells again. Those viruses that no longer grow well can be used as a vaccine. These are attenuated.

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13
Q

How are attenuated pathogenic viruses made by genetic engineering?

A

Viral genes responsible for growth or virulence are mutated or excised. These new viruses maintain immunogenicity but have lost their pathogenicity (avirulent)

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14
Q

What are toxoid vaccines and how are they made?

A

Toxoid vaccines use an inactivated toxin as the antigen.

For example, endotoxins produces by diphtheria and tetanus are inactivated with formaldehyde to produce a toxoid. These substances are rendered non-toxic but maintain antigenicity.

However, these provoke an inadequate immune response by themselves and require co-administration with an adjuvant.

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15
Q

What are anti-idiotype vaccines? What do the terms idiotype and anti-idiotype mean?

A

An idiotype is the immunogenic or paratope region on an aby that finds the ag epitope.

An anti-idiotype aby is a secondary aby that targets the ag binding paratope (FAB) of the primary aby.

An anti-idiotype acts as or resembles an epitope. This can be used as a vaccine.

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16
Q

What targets do therapeutic vaccines have in activating the immune system?

A

These can be used against cancer, chronic viral infections, bacterial infections, or neurodegenerative diseases like alzheimers.

17
Q

What targets to therapeutic vaccines have in generating immune tolerance?

A

Vaccines can be used to generate immune tolerance in autoimmune diseases or to transplanted organs.

18
Q

What are adjuvants; what do they do and what do they usually contain?

A

These are insoluble agents that enhance the antigenicity of co-administered ag. These often act to delay the release of antigen and enhance uptake and presentation of antigenic pathogens/particels by macrophages. They can contain depot components, aluminum compounds, muramyl dipeptides, corynebacterium parvae or other components of or inactivated pathogens.

19
Q

What is Freund’s Complete Adjuvant?

A

This is an experimentally used suspension of dead mycobacterium in oil, water, and detergent.
This stimulates an immune response to weak immunogens by activating macrophages.
The detergent keeps Ag and oils in suspension facilitating a slow depot like release.

20
Q

What less intense bacterial components can be used over Freund’s complete adjuvant? What are the pros and cons of using these?

A

Muramyl dipeptides from mycobacteria can be used but they are less immunogenic. C. parvum extracts can also be used. These are less intense, and multiple doses can lead to macrophage overstimulation and lymphoid hyperplasia.

21
Q

Why are aluminum compounds used in vaccine production?

A

These are the main adjuvant used clinically.
Alum enhances immunostimulation and slows Ag release.
This does cause pain at site of injection.
Aluminum phosphate and aluminum hydroxide are used. These are insoluble in nature.

22
Q

How can vaccines be administered?

A

ID, SC, IM, oral, lipid micelle, transgenic plant / food.

23
Q

Explain how immune stimulatory compounds enclosed in a lipid micelle could result in provoking an immune response.

A

ISCOMs (peptide enclosed in lipid barrier) are injected.

These fuse with an APC allowing peptides to enter the cytosol.

Peptides transported into ER where they bind MHCI.

MHC1 recognized by CD8 T cells.

24
Q

How are bacterial vaccines manufactured?

A

Organism grown in broth.
Inactivation with formaldehyde or phenol (heat).
Separation of inactivated bacteria by centrifugation.
Resuspension in isotonic solution for injection.
Dialysed to further purify.

25
Q

How are viral vaccines manufactured?

A

These cannot be grown sufficiently on inanimate media.
These are grown in embryonic egg, cell embryonic cultures, human and monkey cell cultures.
Virus is separated from culture after growth.
Purification done to reduce hypersensitivity reactions. Resuspension in isotonic solution.

26
Q

What is iatrogenic disease?

A

This is illness as a result of medical treatment.
Vaccination results in febrile (fever, aches, malaise) symptoms.
Vaccination with live viruses can cause disease if the viruses regain pathogenicity.

27
Q

What does primum non nocere mean?

A

First do no harm.

28
Q

How can vaccination success lead to outbreaks of a disease?

A

As vaccination increases, herd immunity increases. As herd immunity increases, there is less disease incidence. When there is less incidence, controversy and fear about the vaccine may increase. This results in less people getting vaccinated. With less vaccination, there is less herd immunity, and outbreaks in the non-immunized population can occur.

29
Q

What is the DTP / dTAP vaccine?

A

Vaccination against diphtheria, pertussis, tetanus.

30
Q

What is the relationship between measles, subacute sclerosing pan encephalitis, and vaccination?

A

Late phase measles infection causes SSPE which results in paralysis from viral infection of the spinal cord and brain. Vaccines have reduced incidence from 100 000 to under 1000.