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PABI 6100 Immunobiology- Exam > Vaccines and Vaccination > Flashcards

Vaccines and Vaccination Flashcards

1
Q

What is immunity?

A
  • state of protection from a particular infectious disease
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2
Q

What is immunization?

A
  • process of producing a state of immunity in a subject
  • deliberate induction of an immune response by exposing an individual to a specific antigen
  • often called vaccination when used to induce a protective immune response to a microbial pathogen
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3
Q

What is vaccination?

A
  • deliberate induction of adaptive immunity to a pathogen by injecting dead/ attenuated (nonpathogenic) live form of pathogen or its antigens (vaccine)
  • intentional administration of a harmless/ less harmful form of pathogen to induce a specific adaptive immune response that protects the individual against later exposure to the pathogen
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4
Q

What is a vaccine?

A
  • preparation of immunogenic material used to induce immunity against pathogenic organisms
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5
Q

How can immunity be achieved?

A
  • Passive Immunity > natural passive/ artificial passive
    > recipient not making own antibodies so temporary
  • Active Immunity > natural active/ artificial active
    > make own antibodies
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6
Q

What are the 4 ways immunity can be achieved?

A
  • Natural Passive > maternal placenta/ breast-feeding
  • Artificial Passive > transfer of preformed antibodies (antiserum)
  • Natural Active > infection/ recovery
  • Artificial Active > immunization (vaccines)
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7
Q

What is passive immunization?

A
  • delivery of preformed antibody
  • occurs naturally > maternal IgG crosses placenta to fetus/ IgA in breast milk
  • can be achieved by injecting recipient with preformed antibodies (antiserum) from other immune individuals
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8
Q

What is antiserum?

A
  • fluid component of clotted blood from an immune individual
  • contains antibodies against antigen used for immunization
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9
Q

What conditions warrant the use of passive immunization?

A
  • immune deficiency > individual can not make antibodies
  • toxin/ venom exposure with immediate threat to life > not enough time to make antibodies
  • exposure to pathogens that cause death faster than an effective immune response can develop
  • protect travelers/ healthcare workers who experience exposure to pathogens they lack immunity for
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10
Q

What are the risks associated with injection of preformed antibody?
(artificial passive immunity/ passive immunization)

A
  • immune response to antibody > if Ab made in another species
    > anti-isotype response
    > has serious complications
  • immune response to antibody > if human gammaglobulin used
    > anti-allotype response
    > much less serious than anti-isotype response
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11
Q

What is an anti-isotype response?

A
  • immune response to injection of preformed antibody > antibody made in another species > serious complications
  • production of IgE against horse-specific determinants
    > IgE-horse antibody immune complexes induce mast cell degranulation > systemic anaphylaxis
  • production of IgG/ IgM antibodies specific for foreign antibody
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12
Q

What has been a major impediment to monoclonal antibody therapy in humans?

A
  • antibodies made by immunizing nonhuman species
  • humans can develop antibody response against nonhuman antibodies
  • leads to allergic reactions/ anaphylaxis
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13
Q

How can antibodies be engineered to reduce their immunogenicity in humans?

A

Humanization
- process of making antibodies that are not recognized as foreign by immune system

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14
Q

What are the suffix naming conventions to identify the type of antibody?

A
  • omab > murine monoclonal antibodies (fully mouse)
  • ximab > chimeric antibodies > entire variable region spliced into human constant regions
  • zumab > humanized antibodies > murine hypervariable regions spliced into human antibody
  • umab > derived entirely from human sequences (fully human)
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15
Q

What was the first vaccine developed?

A
  • Edward Jenner > inoculated with cowpox to prevent smallpox
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16
Q

What is a primary vs secondary response?

A
  • primary response > first encounter with antigen
    > initial lag phase/ Ab levels plateau
  • secondary response > second exposure to same antigen
    > very rapid/ intense antibody secretion (memory)
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17
Q

What are some features of effective vaccines?

A
  • must induce long-lasting protection while being safe/ inexpensive
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18
Q

What are the 4 phases of vaccine clinical trials in humans?

A

Phase I > assess human safety > monitor small number of volunteers for adverse side effects
Phase II > effectiveness against pathogen is evaluated > test for measurable immune responses to immunogen > many vaccines fail at this stage
Phase III > expanded volunteer populations > natural evidence of protection against “real thing” is desired outcome
Phase IV > after marketing/ distribution > long-term impacts/ monitor safety and effectiveness (after vaccination)

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19
Q

What is herd immunity/ how does it work?

A
  • population scale immunity
  • as a critical mass of people acquire immunity (either through vaccination/ recovery from infection) > they can serve as buffers for rest
  • works by decreasing the # of individuals that can harbor/ spread the infectious agent > reduces chances that susceptible individuals will become infected (indirect protection)
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20
Q

How many people must be vaccinated to prevent virus spread?

A

1-1/R0
R0- # of new infections generated by first infectious individual in a completely susceptible population

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21
Q

What is the effective reproductive number?

A

RE- reflects # of new infected individuals per 1 infectious individual
- defined by product of R0/ proportion of population that is susceptible

22
Q

What is the herd immunity threshold?

A
  • fraction of the population that is susceptible when RE falls below 1 and the # of infectious individuals peaks
23
Q

What are 8 different types of vaccines?

A
  • live attenuated
  • inactivated/ killed
  • toxoid (inactivated exotoxin)
  • subunit
  • conjugate
  • recombinant vector
  • DNA vaccines
  • RNA vaccines
24
Q

How are live attenuated vaccines made?

A
  • microorganisms are attenuated (disabled) > lose ability to cause significant disease but retain capacity for slow/ transient growth within an inoculated host
  • attenuation can be achieved by growing bacterium/ virus for prolonged periods under abnormal culture conditions
25
Q

What are some pros/ cons of live attenuated vaccines?

A

Pros- more efficient production of highly effective memory cells > due to capacity for growth > prolongs exposure to epitopes on attenuated organisms
- promote both humoral/ cell-mediated response
Cons- may mutate/ revert to more virulent form > disease risk
- can be associated with complications like in natural disease
- may require cold chain for stability during transport

26
Q

What is an example of a naturally attenuated agent?

A
  • Vaccinia virus (cowpox) > unable to cause disease in host, while able to immunize against smallpox
27
Q

How are viruses traditionally attenuated?

A
  • by selecting for growth in nonhuman cells
  • virus is isolated from patient/ grown in cultured human cells
  • virus adapted to growth in different species > until grows only poorly in human cells (due to mutations)
  • attenuated virus grows poorly in human host > produces immunity but not disease > can be used as vaccine
28
Q

How can live-attenuated viruses be made safer?

A
  • recombinant DNA technology
  • identify gene in virus required for virulence but not growth/ immunogenicity > multiply mutate/ delete gene > create avirulent/ nonpathogenic virus that can be used as vaccine
29
Q

What is the current approach/ ideal approach to vaccination against influenza?

A
  • current approach > killed virus vaccine > reformulated annually based on prevalent virus strains
  • ideal approach > attenuated live organism that matched prevalent virus strain
30
Q

What is the problem with the killed virus current approach to vaccination against influenza?

A
  • Antigenic shift- Influenza escapes original immune response (changes every year)
  • Heterosubtypic immunity- weak protection from previous infections of different subtypes seen in adults but not children
31
Q

What is an example of a live attenuated vaccine?

A

OPV- used for decades worldwide
- colonizes intestine > induces IgA/ IgM/ IgG production
- original form consists of 3 attenuated strains of poliovirus
- requires boosters (unlike other attenuated viruses) since 3 strains interfere with each other’s replication
- first immunization > 1 strain predominates > induces immunity to strain
- second immunization > immunity by previous immunization limits growth of previously predominant strain > enables one of remaining 2 strains to colonize/ induce immunity
- third immunization > immunity to all 3 strains achieved

32
Q

How are inactivated/ killed vaccines made?

A
  • pathogen incapable of replication but still induces an immune response
  • heated/ chemically treated to inactivate
    > heat inactivation causes protein denaturation > alters epitopes
    > chemical inactivation is more successful
33
Q

What are some pros/ cons of inactivated/ killed vaccines?

A

Pros- no reversion to pathogenic form
- often more stable > ease of storage/ transport
Cons- often require booster shots
- less effective in inducing cell-mediated immunity (predominantly humoral)
- potentially dangerous if not all pathogen inactivated/ killed

34
Q

What are subunit vaccines/ what are the 3 most common applications?

A
  • use specific purified macromolecules derived from pathogen
    > inactivated pathogen exotoxins (toxoids)
    > isolated capsular polysaccharides/ surface glycoproteins
    > purified key recombinant protein antigens
35
Q

What is a limitation of subunit vaccines?
- especially in polysaccharide vaccines

A
  • inability to activate TH cells
  • activate B cells in T-independent manner > little class switching/ no affinity maturation/ little memory cell development
  • can be avoided by conjugating polysaccharide antigen to protein carrier > TH response against both protein/ polysaccharide
36
Q

What are toxoid vaccines?

A
  • inactivated exotoxins induce anti-toxoid antibodies > bind to toxin/ neutralize its effects
37
Q

What is the rationale for subunit vaccines consisting of capsular polysaccharides?

A
  • antiphagocytic properties of polysaccharide capsules contributes to virulence of some bacteria
  • vaccinations with capsular polysaccharides induce formation of opsonizing antibodies > enhance phagocytosis
38
Q

How is DNA recombinant technology used in designing subunit vaccines?

A
  • used to produce purified toxins
  • used to produce surface viral/ bacterial/ protozoal antigens
  • ex) Hepatitis B vaccine > clone gene for HBsAg > express in yeast cells > grow recombinant cells > allow HBsAg to accumulate/ harvest from yeast cells > release recombinant HBsAg
39
Q

What are recombinant vector vaccines?

A
  • genes that encode antigens of pathogens are introduced > attenuated viruses/ bacteria
  • attenuated organism serves as vector > replicating within vaccinated host/ expressing gene it carries from pathogen
  • ex)- foreign gene into vaccinia virus vector
40
Q

What are some pros/ cons of recombinant vector vaccines?

A

Pros- prolong immunogen delivery/ encourage cell-mediated responses
- do not revert to pathogenic forms like live attenuated vaccines
Cons- stability issues

41
Q

What are DNA vaccines?

A
  • plasmid DNA injected directly into muscle of recipient
  • DNA integrates > host chromosomal DNA
  • aims to deliver DNA plasmid to APCs near injection area
42
Q

How can immune responses to DNA vaccines be enhanced?

A
  • booster shot with protein antigen > DNA prime/ protein boost strategy
  • include supplementary DNA sequences in vector > genetic adjuvants
43
Q

What are some pros/ cons of DNA vaccines?

A

Pros- induce both humoral/ cell-mediated immunity
- prolonged expression of antigen > enhances memory
- no refrigeration needed
- same plasmid vector can be engineered to insert DNA encoding a variety of proteins > simultaneous manufacture of DNA vaccines for different pathogens
Cons- still no DNA vaccines available
- usefulness to protect against infection disease is unknown

44
Q

What is the major drawback of RNA vaccines?

A
  • need to be stored at very low temperatures from production to time of use (relative instability) > increases cost of delivery
45
Q

What are 2 ways vaccine immunogenicity can be improved?

A
  • adding a conjugate (immunogenic protein)
  • adding a multivalent compound (phospholipid > ISCOM/ liposome > to get intracellular)
46
Q

What is an example of a conjugate used to improve vaccine immunogenicity?

A
  • Hib vaccine- conjugate of bacterial surface polysaccharide (non-immunogenic)/ tetanus toxoid protein (highly immunogenic)
  • boots B cell response > anti-polysaccharide antibodies
47
Q

What is an example of a multivalent used to improve vaccine immunogenicity?

A
  • incorporate membrane proteins from pathogens > ISCOMs/ liposomes > can deliver agents inside cells so mimic endogenous antigens > cell-mediated immunity
  • serve as adjuvants
48
Q

What is an adjuvant?

A
  • any substance that enhances immune response to antigen to which it is mixed
49
Q

Why is route of vaccination an important determinant of success?

A
  • ideal vaccination induces host defences at point of entry of infectious agent > stimulation of mucosal immunity is important goal
  • most vaccines given by injection > many disadvantages
50
Q

What is an example of the impact route of vaccination has on success?

A
  • intranasal vaccine against influenza > mucosal antibodies > more effective than systemic to control upper respiratory tract infection
  • systemic antibodies from injection > more effective to control lower respiratory tract disease > major cause of mortality

PABI 6100 Immunobiology- Exam (6 decks)

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