Week 8: Vaccinations Flashcards

1
Q

What is immunization?

A

The process of generating a state of immunity against disease-causing pathogen

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2
Q

What is a vaccination?

A

Provides immunological memory of pathogens without having to be infected by a pathogen but instead by a vaccine

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3
Q

What are vaccines?

A

Contain antigen from the pathogen or synthetically produced antigen that indue an immune response without causing disease

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4
Q

What is an active immunization?

A
  1. Induce immunity and memory through a vaccine
  2. Activation of B and T cells result in formation of memory cells
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5
Q

What are booster vaccination?

A

Required to achieve protective immunity to many pathogens

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6
Q

What is herd immunity?

A
  1. Vaccines can’t protect individuals who haven’t been
  2. If enough people are vaccinated, transmission of pathogen can be prevented and indirect protection is provided
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7
Q

What are the advantages and challenges of vaccines?

A
  1. Should be safe
  2. Should be effective at prevention infection
  3. Delivery strategy should be achievable in desired populations
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8
Q

Wht occurs during immunological memory?

A
  1. Development of a population of effector cells
  2. Build memory
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9
Q

How do we build memory?

A
  1. Develop long lived memory B and T cells by stromal cells in BM
  2. High levels of high affinity pathogen specific antibodies
  3. Abs levels remain high for month post ifnfection
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10
Q

What is primary immune response?

A
  1. Low affinity IgM Ab
  2. B cells undergo: SHM, affinity maturation, isotope switching, T cell help
  3. Memory B cells are made from clones that are making the highest affinity antibody against an antigen
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11
Q

What are the goals of primary immune response?

A
  1. Make effector cell destroy pathogen
  2. make long-lived memory T and B cells
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12
Q

What is secondary immune response?

A
  1. Faster
  2. Stronger
  3. Memory cells are activated more easily
  4. Antibodies have a greater affinity than primary
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13
Q

What are the characteristics of B cells in sensory immune response?

A
  1. Greater number of pathogen specific memory B cells
  2. Produce higher affinity isotope switched antibodies
  3. Low affinity naive B cells are inhibited in the secondary immune resposne
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14
Q

What are the properties of memory cells?

A
  1. Don’t require regular stimullation
  2. Persists for years
  3. Remain in quiescent state, but repilicate to replenish the population
  4. Antigen independent activation and proliferation driven by cytokine signaling
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15
Q

How do memory T cells differ from Naive T cells?

A
  1. Recirculate in peripheral tissue
  2. Activated in site of infection
  3. Naive circulate in secondary lymphoid tossue
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16
Q

What are memory B cells?

A
  1. Recirculate between the blood and lymph
  2. Have affinity receptors that are more sensitive to specific antigen
  3. Express high levels of MHC class 2 and costimulatory molecules
  4. Smaller amount of pathogen can trigger B cell response
  5. Less time to differentiate to plasma cells
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17
Q

What is the goal of vaccine efficacy?

A

Safely generate a desire immune response against pathogen without causing an infection

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18
Q

What immunogenicity are we looking for?

A

Capable of generating a long lasting protective antibody and T cell response

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19
Q

What are iummunogens?

A

Antigens that contain epitopes that induce an immune response and also the targets of that response

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20
Q

What are adjuvants?

A
  1. Provide danger signals to immune cells to lead to a greater antigen uptake by APC
  2. Cause local sentinel cell activation leading to the production of chemokines that dray monocytes, neutrophils, MP, and DCs at injection site
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21
Q

How are vaccines biodistributed?

A
  1. Typically administered by a bolus injection into the muscle, skin, or subcutaneous space (parenteral vaccines).
  2. Vaccine is transported through lymphatic vessels to draining LN by DCs to present antigen to T and B cells.
  3. Soluble vaccine components can also enter the blood and be transported to the liver and spleen and lead to lymphocyte activation in these SLTs.
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22
Q

What is the goal of vaccine response?

A

Generate memory T and B cella and plasma cells

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23
Q

How do vaccines generate an immune response?

A
  1. DC cells capture antigen from vaccine, process and present antigen to T cells within the draining lymph node.
  2. DCs secrete cytokines to help with T cell proliferation.
  3. BCR on B cells can bind to soluble vaccine antigen to become activated.
  4. Helper T cells (TFH cells) interact with B cells leading to a germinal center response.
  5. In the GC, B cells clonally expand and undergo affinity maturation.
  6. B cells can differentiate into short and long lived plasma cells, memory b cells
24
Q

How does dose affect vaccine response?

A
  1. Dose of antigen has consequences on the quality of T and B cell response.
  2. Dependent of antigen dose and APC availability
  3. Greater antigen availability increases the differentiation of Helper T cells into TFH cells.
  4. TFH and B cell interactions are also enhanced by increased antigen availability.
25
Q

What is Complete Freund’s Adjuvant?

A

Water in oil emulsion that contains heat-killed mycobacteria (strong TH1 response_

26
Q

What is imcomplete freund’s adjuvant?

A

Water in oil emulsion that cause strong TH2 response

27
Q

What is SqualVax?

A

Oil in water emulsion made with squalene that Attracts macrophages to the site of vaccination and Causes a strong immune response (higher antibody production and both TH1 and TH2 cell responses)

28
Q

What is alum?

A

Aluminum phosphate or aluminum hydroxide binds antigens and concentrates them at the site of injection to enhance antigen presentation
Good for stimulating TH2 responses

29
Q

What is AS04?

A

alum with an TLR4 agonist that activates PRRs

TLR4 (e.g. LPS) encourages TH1 responses

30
Q

How do adjuvants stimulate immune response?

A
  1. Included to enhance the immune response (immunogenicity) to a vaccine
  2. Promoting inflammation recruits more immune cells to the area, enhance effectiveness
    Included to enhance the immune response (immunogenicity) to a vaccine
  3. Promoting inflammation recruits more immune cells to the area, enhance effectiveness
31
Q

What is genetic drift?

A

Frequent changes to the virus in one file season

32
Q

What is genetic shift?

A

When Flu viruses from different species infect the same cell and the 2 viruses generate a new hybrid virus with new characterisitcs

33
Q

How do highly mutable viruses escape memory?

A
  1. Antigenic drift from the viral strain of the first infection prevents effective memory cells from being produced
  2. The secondary response is limited to epitopes shared by the infecting strain and the original strain
  3. Due to the this slight overlap of antigens, both naïve and memory B cells are activated reducing an effective response.
  4. This is only overcome when the strain of influenza lacks all epitopes of the original strain then a new “primary response” is generated.
34
Q

What is the goal of active immunization?

A

Trigger the adaptive immune response so that long-lived immunological memory will develop

35
Q

What are methods of active immunization?

A

Natural exposure to infectious agent or similar agent (unintended)
Administration of a vaccination (deliberate)

36
Q

What is passive immunity?

A
  1. Placental transfer of maternal IgG antibodies
  2. Dimeric IgA from maternal breastmilk
37
Q

What vaccines interfere with maternal antibodies>

A
  1. DTaP
  2. Measles
  3. MMR
38
Q

What are boosters/

A

Repeated vaccination that are often needed to generate an adequate memory repsonse

39
Q

What are the pros of live attenuated?

A
  1. Produces the most robust response (most similar to the real pathogen)
  2. Pathogen maintains ability to grow within host which provides prolonged exposure to pathogen immunogens
  3. Most provide lifelong immunity with a single dose
  4. Organism is attenuated (disabled) by growing the pathogen (virus or bacteria) in abnormal growth conditions
40
Q

What are the cons of live attenuated?

A
  1. Risk of reversion pathogen may mutate to virulent form in host
  2. Associated with complications similar to those seen in the natural disease
  3. Risk of replicating in a uncontrolled manner in immunocompromised individuals
  4. Requires refrigenration
41
Q

What are the pros of killed whole organism?

A
  1. Pathogen is treated with heat or chemicals that kill it
  2. Pathogen is unable to replicate bu preserves immunes making it capable of inducing an immune response
  3. Pose no risk to immunocompromised
  4. Stable vaccine that doesn’t require refrigeration
42
Q

What are the cons of killed whole organism?

A
  1. Require repeated boosters to generate protective immunity
  2. Produce primarily a humoral repsonse
  3. Must be tested to ensure proper inactivation of pathogen
43
Q

What are subunit vaccine?

A

Immunogenic purified macromolecules derived from the pathogen

44
Q

What are the macromolecules in a subunit?

A
  1. Isolated capsular polysaccharaides
  2. Recombinant proteins
  3. Purified protein antigens
45
Q

What are the pros and cons of subunit?

A
  1. Requires multiple antigens
  2. Non-live vaccines so no risk of infection
46
Q

What are toxoid?

A
  1. No live vaccine, no risk
  2. diphtheria and tetanus produce exotoxins
  3. Toxoids are inactivated exotoxins
  4. Generate high affinity anti toxin antibodies
47
Q

What is the function of an anti-toxin?

A

Neutralize the toxins that are produced by exotoxin secreting bacteria

Stable and long lasting

48
Q

What ae protein polysaccharide conjugate?

A
  1. Polysaccharide (non-immunogenic) is linked to a carrier protein that is immunogenic (e.g. toxoid)
  2. Provides protection against encapsulated bacteria
  3. Vaccine to H. influenzae is a conjugate of capsular polysaccharide with tetanus toxoid
  4. Engages T Helper cells to generate a high affinity IgG antibody response
  5. Generates memory B and T cells
  6. Is able to provide protection to infants at ~2 months or older
  7. Non-live vaccine so no risk of infection
49
Q

What are virus like particle?

A
  1. Particle made of viral proteins
  2. Mimic the native virus
  3. Lack the viral genome and can’t replicate
50
Q

What are outer membrane vesicles?

A
  1. Particles made of bacterial antigens
  2. Structurally mimic the native bacteria including outer membrane
  3. Non-live vaccine so no risk of infection
51
Q

What is viral vectored?

A
  1. Gene that encodes the antigen is inserted into a plasmid vector adjacent to vaccinia promoter
  2. When plasmid is cultured with vaccinia virus, the DNA is inserted into the vaccinia virus genome by homologous recombination.
  3. Cells containing the recombinant vaccinia are selected.
  4. Genes from virulent pathogens can be put into safe attenuated viruses to be delivered.
52
Q

What are nucleic acid vaccine?

A
  1. mRNA is delivered in a lipid coat similar to liposome
  2. mRNA is converted into protein by host ribosomes and then is processed and presented by MHCs to T cells
  3. Stimulates both CD8 and CD4 T cells
  4. Induces generation of high-affinity antibodies
  5. Memory T and B cells
53
Q

What are the factors that affect vaccination efficacy?

A
  1. Age
  2. Children younger than 2
  3. Adult over 75
  4. Adherence to vaccination schedule
54
Q

What are the side effects of vaccines?

A

injection site pain, redness and swelling, fever, malaise, and headache

55
Q

What are the rare side effects>

A

Anaphylaxis and idiopathic thrombocytopenic purpura