Immunity and Vaccination Flashcards
What are the two broad categories for immunization and what is the difference?
- Active- immunogen is injected to elicit an adaptive immune response
- Passive- Ab or cells are injected that provide protection against an infection or toxin
What is an immunogen?
A substance that is able to elicit a humoral response when injected. It does not provide immediate protection
What are the two subdivisions of active immunization? What is an example of each?
- Natural (unintended)- the person gets infected
2. Artificial - vaccination
What is an example of natural passive immunization?
The transfer of IgG from the mother to the baby through the placenta
What is an example of artificial passive immunization?
Passive antibody therapy like:
- serum therapy
- human IgG transfer
What feature of the smallpox virus allows it to be completely eradicated where viruses like influenza can mutate and resurface?
The only host species for smallpox is the human so the virus can’t go into pigs or birds, etc, mutate, and reenter human hosts.
Influenza has multiple host species
Roughly how many people have adverse reactions to vaccines annually?
Who generally experiences these adverse reactions?
100s to 1000s.
It generally affects people who are already immunosuppressed.
Why are vaccines given to infants and young children starting as early as one month of age?
Because diseases are most dangerous to infants due to their weak/underdeveloped immune system
Why do some people resist giving infants/small children immunizations?
Because a lot of the vaccines are active so that memory and effector cells can be generated. This can cause discomfort for the baby.
What are the six main considerations one must take into account when designing a vaccine?
- Safety
- Protective against disease
- Sustained protection for several years
- Induce immunity appropriate for the pathogen (Neutralizing, T-cell mediated, etc)
- Inexpensive
- Biologically stable, few side effects, etc
What is meant by the safety of a vaccine?
The vaccine should not cause illness or death. This is tricky because you need to give enough antigen to stimulate innate and adaptive immune response without pathogenesis.
What must be a feature of a vaccine for a pathogen that preferentially infects cells that cannot be regenerated? (like polio virus affecting neurons)
It must be able to introduce neutralizing antibodies to prevent infection
What must a vaccine for viruses and other intracellular pathogens be able to induce?
T-cells because this type of pathogen requires cell-mediated immune response
What are the four “practical” considerations when designing a vaccine?
- Low cost
- Biological stability
- Ease of administration
- few side effects
What are the four types of vaccines for infectious diseases in humans?
- Killed bacteria
- Live attenuated and dead viruses
- Toxoid vaccines
- Conjugate vaccines
What is an example of a killed bacteria vaccine and what protection is elicited?
BCG (for TB) and cholera
It elicits an antibody response
What is an example of an attenuated viral vaccine?
What protection is elicited?
- Smallpox, polio, varicella, mumps, rabies
2. Antibody AND cell-mediated immune response
What is an example of a subunit (antigen) or toxoid vaccine?
What protection is elicited?
Tetanus and diphteria toxoid
They elicit an antibody response
What is an example of a conjugated vaccine?
What protection is offered?
Influenza
Antibody response that is Th-dependent
How long are protective levels of Ab present following a primary infection?
How long are memory B and T cells generated during the primary infection able to persist?
Ab- few weeks
Memory T&B - years
When a second infection occurs, memory B and T cells allow for the response to be ___________ with an _______ level of IgG. The antibodies are able to _______________/
quicker, increased
The antibodies are able to persist for months or years as opposed to the few weeks they persist after the initial infection
Why are antibodies able to persist for such a long time following second infection?
Because of the production of long-lived plasma cells in the bone marrow
The efficacy of immunologic memory in protecting from a second disease event is dependent on __________________.
the length of the incubation period prior to the onset of the disease
What type of infection is not effectively inhibited by the rapid and larger secondary adaptive immune response?
Acute onset with a short incubation period
What type of pathogen will be eliminated by the accelerated adaptive immune response?
a pathogen with a long incubation period
Re-infection with an acute disease pathogen will elicit a much ___________ case of the disease that has a _____________ because the secondary response will develop ____________ and generate __________________.
milder, shorter duration
The secondary response will develop quickly and generate large quantities of antibody and effector T cells
What is the KEY aspect of developing a efficacious immunization protocol?
How is this achieved?
- You need to produce long-lasting high titers of pathogen-specific Ab
- This is achieved by repeated immunization (boosters)
With each repeated immunization, the immune response becomes virtually exclusively _____ mediated and the amount of antibody _______as does the ________ of the antibody.
IgG
With each immunization the amount of Ab increases and the affinity for the immunogen does as well
What are the 4 major benefits of repeated immunization?
- the Ab produced becomes almost exclusively IgG
- The amount of Ab increases
- the affinity of the Ab for the immunogen increases
- Differentiation into long-lived plasma cells occurs so Ab can protect for years
Why does a tertiary immunization increase the affinity of the Ig for the pathogen?
The B-cells form germinal centers and go through affinity maturation (somatic mutation and FDC selection)
What are three benefits for using an attenuated vaccine?
- Immunization is natural and elicits immunity in appropriate components of the immune system
- herd immunity can develop
- Simple and inexpensive
What is meant by herd immunity?
What type of vaccination do you typically see it with?
It means that even if a person is not personally vaccinated, the attenuated strain will spread to them and they will also garner immunity
What are the two basic strategies for attenuating a virus?
- Culture the virus on another related species (like monkey). The virus will mutate to allow it to grow better in monkey cells. The virus can no longer grow well in humans because it has adapted to growing in monkey cells. Then inject it back into humans to confer immunity.
- Use recombinant DNA and remove the pathogenic/virulent genes from the viral genome
What is the major drawback of using attenuated viruses for vaccines?
The virus has the potential to revert back to virulent form while replicating in host tissue.
This is extremely rare and usually only will occur in immunocompromised patients.
What was the first investigated attenuated vaccine strain?
What were its 4 major benefits?
The polio or Sabin vaccine
- oral administration (easy)
- cheap
- safe, effective, induced immunity to all 3 strains
- herd immunity because it replicates in the intestine and can infect unvaccinated ppl
What was the drawback of the polio vaccine?
How many people does it infect?
It caused paralysis in 1/2.7 million people vaccinated (mostly immunodificient)
Why would attenuated viruses have more negative effects for immunodeficient people than those with good immune systems?
because attenuated viruses can have pathogenicity (just really reduced)
but if a person is immunocompromised, the virus might not be attenuated enough for them
What type of pathogen do we make conjugated vaccines for?
Bacteria or immunogens that have a polysaccharide coat or capsule
Why don’t we immunize with killed whole bacteria?
There are deleterious effects
Why is it necessary to have antibodies in serum against bacteria with polysaccharide coats?
Because the antibodies are necessary to opsonize these bacteria
Why don’t we use purified polysaccharides as a vaccine against bacterial capsules?
Because purified polysaccharide would act as a TI-2 antigen meaning that it activates B cells without CD4 T cell involvement. They would only produce IgM and IgG2 and would make no memory cells.
What immunoglobulins would be made if the polysaccharide was used as the vaccine?
IgG2 and IgM
How do we make conjugated vaccines?
Covalently attach a peptide to the polysaccaride structure that is the same epitope as the bacterial capsule. The peptide will get taken up by the cell and presented as MHCII/peptide complex. This will involve CD4 T cells in the B cell maturation, will generate a germinal center and you will have affinity maturation, class switching and memory cell generation
How many vaccines are given to children before the age of 2 months?
What type of vaccine is avoided and why?
6- none of which are attenuated organisms because the baby doesn’t have a good established immune system yet
Concerns have been raised over early immunization because they have been linked to: (4 things)
Most likely though, these are probably linked to_____________
- food allergies
- asthma
- autoimmunity
- autism
Most likely these should be linked to environmental factors not vaccines
What vaccine has been frequently linked to autism (but has been shown to have no relationship in science journals)?
What type of vaccine is it? When is it given?
MMR (measles, mumps, rubella) which is an attenuated vaccine given after 1 year of life
One current strategy for vaccine development has been to focus on improving the properties of _____________ and developing approaches to shift immune response toward _____________________.
adjuvants (combos of substances that make adaptive immune response with less virulent antigens)
shifting immune response to making high titered antibody production
What are scientists looking into as potential adjuvants?
using ligands for TLR receptors
What strategy are scientist currently working on for the development of viral vaccines?
What specific genome are they looking at?
Recombinant DNA to create new viral vectors without their virulence genes.
They are looking to modify the vaccinia poxviral genome to carry antigens from other pathogens
What would using vaccinia poxviral genome to carry and express protein antigens from other pathogens allow us to do?
This would allow immunization against multiple pathogens with a single vaccine
What type of infection are conjugated vaccines typically used for?
bacterial infections where there is a polysaccharide coating or capsule as a virulence factor
Why are Ab necessary for pathogens that have carb capsules?
because the Ab obsonize the bacteria to make them more easily phagocytosed by macrophages
Why don’t we use killed whole bacteria as vaccines for pathogens with a capsule?
these preparations are prone to deleterious side effects
Why don’t we use purified polysaccharides that resemble the bacterial capsule be used as a vaccine?
because they are TI-2 antigens so they would not activate germinal centers for affinity maturation and class-switching, and wouldn’t generate memory cells.
This makes them a poor immunogen
What is meant by conjugate vaccine?
A protein carrier is covalently attached to the polysaccharide so that it will be endocytosed and it will make the polysaccharide (TI2) T-cell dependent by increasing MHC II presentation so B and T cells can be activated to generate germinal centers and make memory response
TI-2 antigens (polysaccharide coat) stimulates B cells without involving ________________. This does not result in the production of ______________ and it only produces ____and _____ Ig’s.
CD4 Th cells
so it does not produce B or T memory cells and only produces IgM and IgG2 antibodies
How many vaccines are started by the second month of life?
What type of vaccine is avoided in this early vulnerable immune stage?
6
Attenuated vaccines are avoided because the babies immune systems are still week
What are the diseases for which effective vaccines are not yet available?
- respiratory disease
- HIV/AIDS
- Malaria
- TB
- Diarrheal disease
- Hep C
- Worms
- Schstosomiasis
- Measles
What are the two ways mothers can transfer passive immunity to their babies?
- through the placenta (IgG)
2. via colostrum in breast milk (IgA)
Why is the passive immunization of babies through the placenta and breast milk especially effective?
The antibodies the mother produces are in response to immunogens prior to and during the pregnancy so the Ig are poised to handle a wide range of antigens while the babies immune system is developing (by the end of the first year of birth)
When does the baby start producing their own IgM? IgG? IgA?
IgM- 6 months
IgG and IgA at around 9 months
When does the serum level of IgG and IgA in an child surpass the IgM levels?
4 years of age
When is the peak of protection (most antibodies) from the maternal IgG?
9 months
What is the clinical use of passive immunity?
- against toxin producing pathogens (diptheria, tetanus)
2. against snake or spider venom
What is the difference between heterologous serum and homologous serum?
Heterologous is from a different species (like a horse) and the body can make antibodies against the horse antibodies
Homologous is from the same species
What is the difference between a toxoid and toxin?
Toxin is the virulent strain and toxoid is attenuated
What happens if a heterologous serum is used for passive immunization?
The body makes anti-serum for the foreign Ab and clear the protective Ab from circulation.
Why can’t you use the same heterologous serum twice?
The person will develop serum sickness because they have antibodies against the heterologous Ab.
What type of hypersensitivity is associated with serum sickness?
Type III because it is Ab against circulating ligand
