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A Quick Glimpse…
 Active vs. Passive Immunization
 Designing Vaccines
 Whole-Organism Vaccines
 Purified Macromolecules as Vaccines
 Recombinant-Vector Vaccines
 DNA Vaccines
 Synthetic-Peptide Vaccines
 Mulvivalent Subunit Vaccines
Two Types of Immunization
 Passive Immunization
– Methods of acquisition include natural maternal antibodies,
antitoxins, and immune globulins
– Protection transferred from another person or animal
 Active Immunization
– Methods of acquisition include natural infection, vaccines (many
types), and toxoids
– Relatively permanent
Acquisition of Passive and Active
Immunity
Passive Immunization
 Can occur naturally via transfer of maternal antibodies across placenta to
fetus
 Injection with preformed antibodies
– Human or animal antibodies can be used
– Injection of animal Ab’s prevalent before vaccines
 Effects are only temporary
Conditions Warranting Passive
Immunization
1. Deficiency in synthesis of Ab as a result of congenital or acquired
B-cell defects
2. Susceptible person is exposed to a disease that will cause
immediate complications (time is the biggest issue)
3. Disease is already present
Common Agents For Passive
Immunization
The Immune System and Passive
Immunization
 The transfer of antibodies will not trigger the immune system
 There is NO presence of memory cells
 Risks are included
 Recognition of the immunoglobulin epitope by self immunoglobluin paratopes
 Some individuals produce IgE molecules specific for passive antibody, leading
to mast cell degranulation
 Some individuals produce IgG or IgM molecules specific for passive antibody,
leading to hypersensitive reactions
Active Immunization
 Natural Infection with
microorganism or artificial
acquisition (vaccine)
 Both stimulate the proliferation of T
and B cells, resulting in the
formation of effector and memory
cells
 The formation of memory cells is
the basis for the relatively
permanent effects of vaccinations
Principles Underlying Vaccination
 Concept of Immunity
– Self vs. Non-self
– Antigen specificity
– Indicated by presence of effector cells
– Protection from infectious diseases using above
methods
Vaccinations
Boosters (multiple inoculations) are required
Interference of passive maternal antibodies
Effectiveness of Vaccinations
 Small percentage of recipients will respond poorly
– Role of genetic determinants
 Herd Immunity
– Majority of population is immune, so chance of susceptible individual
contacting infected individual is low
– Measles Epidemic
Herd Immunity
 Factors affecting herd immunity
– Environmental Factors: crowded conditions, seasonal variations
– Strength of Individual’s Immune System
– Infectiousness of Disease: greater the risk of infection, the higher
percentage of people need vaccines to attain herd immunity
 When enough people are vaccinated, chance of germ infecting the
non-immunized population is small
 Can lead to disappearance of diseases (smallpox)
– Vaccination no longer necessary
Quantitative Data
Further Proof of the Effectiveness of
Vaccines
Development of Vaccines
 Common misconception that
activation of the immune system results
in protective immunity
 Multiple factors affect decisions
when making vaccines
1. Activation of specific branch
of immune system
2. Development of
immunological memory
Role of Memory Cells
 Depends on incubation period of pathogen
– Short Incubation Periods
 ex. Influenza
 Symptoms already under way by the time memory cells are
activated
 Repeated immunizations with neutralizing antibodies
– Long Incubation Periods
 ex. Poliovirus
 Enough time to allow memory B cells to respond
Immunological Memory vs. Serum
Antibody Levels
Types of Vaccines
 Whole-Organism
– Attenuated Viral/Bacterial
– Inactivated Viral/Bacterial
 Purified Macromolecules
– Polysaccharide
– Toxoid
– Recombinant Antigen
– Recombinant-Vector
 DNA
 Synthetic Peptide
 Multivalent Subunit
Whole-Organism Vaccines
 Many common vaccines used
consist of inactivated or attenuated
bacterial cells or viral particles
 Includes attenuated and inactivated
vaccines
Attenuated Viral or Bacterial
Vaccines
 Attenuation – to reduce in force, value, amount, or degree; weaken
– Achieved by growth under abnormal culture conditions
– Bacillus Calmette-Guerin (BCG)
– Act as a double edged sword, as they have distinct advantages and
disadvantages…
Advantages of Attenuated Bacterial
or Viral Vaccines
 Advantages stem from their capacity for transient growth
 Prolonged immune-system exposure
 Single immunizations
 Replication within host cells
Exception to the Rule…
 Sabin Polio vaccine consists of 3 attenuated strains of poliovirus
 Colonization of intestine results in immunity to all 3 strains
– Production of secretory IgA and induction of IgM and IgG
 Result is the need for boosters
– Individual strains interfere with one another
 First immunization  one strain predominates in growth
 Second Immunization  immunity generated by previous
immunization limits growth of previously predominant strain
 Third Immunization  same principle as second immunization
Disadvantages of Attenuated
Bacterial or Viral Vaccines
 MAJOR disadvantage is possible reversion
– ex: Rate of reversion of Sabin Polio vaccine is one case in 4 million doses
 Presence of other viruses as contaminants
 Unforeseen postvaccine complications
The Future of Attenuation…
 Genetic engineering techniques provide new methods of attenuation
 Herpes virus vaccine for pigs
 Possible elimination of reversion?
Inactivated Viral or Bacterial
Vaccines
 Methods of inactivation include heat or chemical agents
– End result…. Loss of replication ability
 Difficult to inactivate due to potential for denaturation of epitopes
– Dependence on higher order levels of protein structure
Attenuation vs. Inactivation
Attenuation vs. Inactivation
 Attenuation
– Normally require one dosage to induce relatively permanent immunity
– Primarily cell-mediated in nature
– Despite reliance on cell-mediated immunity, increased IgA response
 Inactivation
– Requires multiple boosters
– Emphasis on activating humoral immunity
However, something very important is missing….
Adjuvants
 Adjuvants are CRITICAL for the use of inactivated vaccines
 Most widely used are aluminum salts (mainly hydroxide or
phosphate)
 Effects include liberation of antigen, chemoattraction, and
inflammation
ISCOMS
 Immunostimulating Complexes
 Multilmeric presentation of antigen/adjuvant
 Enhanced cell-mediated immune response, delayed-type
hypersensitivity, cytotoxic T lymphocyte response, increased Ag
expression associated with MHC II
Additional Facts From Dr. David
Satcher
 Presented a more social rather than
technical view of vaccines
 Barriers to health care include the “7
U’s”
– Uninsured, Under-issued, Under-
represented, Uninspired, Untrusting,
Uninformed
– Ethical Variations
 Significant Social Costs associated with
vaccine-preventable diseases
– $10 billion per year
– 36,000 elderly die yearly from influenza
despite availability of vaccine
– Social impetus is needed to lower these
figures
Impact of Vaccines on Public Health
 Between 1977 and 1980, smallpox was eradicated in the United
States
– Global eradication is currently a major consideration
– Phenomenon of herd immunity
 Measles occurrences at a record low

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Immunology

  • 1.
  • 2. A Quick Glimpse…  Active vs. Passive Immunization  Designing Vaccines  Whole-Organism Vaccines  Purified Macromolecules as Vaccines  Recombinant-Vector Vaccines  DNA Vaccines  Synthetic-Peptide Vaccines  Mulvivalent Subunit Vaccines
  • 3. Two Types of Immunization  Passive Immunization – Methods of acquisition include natural maternal antibodies, antitoxins, and immune globulins – Protection transferred from another person or animal  Active Immunization – Methods of acquisition include natural infection, vaccines (many types), and toxoids – Relatively permanent
  • 4. Acquisition of Passive and Active Immunity
  • 5. Passive Immunization  Can occur naturally via transfer of maternal antibodies across placenta to fetus  Injection with preformed antibodies – Human or animal antibodies can be used – Injection of animal Ab’s prevalent before vaccines  Effects are only temporary
  • 6. Conditions Warranting Passive Immunization 1. Deficiency in synthesis of Ab as a result of congenital or acquired B-cell defects 2. Susceptible person is exposed to a disease that will cause immediate complications (time is the biggest issue) 3. Disease is already present
  • 7. Common Agents For Passive Immunization
  • 8. The Immune System and Passive Immunization  The transfer of antibodies will not trigger the immune system  There is NO presence of memory cells  Risks are included  Recognition of the immunoglobulin epitope by self immunoglobluin paratopes  Some individuals produce IgE molecules specific for passive antibody, leading to mast cell degranulation  Some individuals produce IgG or IgM molecules specific for passive antibody, leading to hypersensitive reactions
  • 9. Active Immunization  Natural Infection with microorganism or artificial acquisition (vaccine)  Both stimulate the proliferation of T and B cells, resulting in the formation of effector and memory cells  The formation of memory cells is the basis for the relatively permanent effects of vaccinations
  • 10. Principles Underlying Vaccination  Concept of Immunity – Self vs. Non-self – Antigen specificity – Indicated by presence of effector cells – Protection from infectious diseases using above methods
  • 11. Vaccinations Boosters (multiple inoculations) are required Interference of passive maternal antibodies
  • 12. Effectiveness of Vaccinations  Small percentage of recipients will respond poorly – Role of genetic determinants  Herd Immunity – Majority of population is immune, so chance of susceptible individual contacting infected individual is low – Measles Epidemic
  • 13. Herd Immunity  Factors affecting herd immunity – Environmental Factors: crowded conditions, seasonal variations – Strength of Individual’s Immune System – Infectiousness of Disease: greater the risk of infection, the higher percentage of people need vaccines to attain herd immunity  When enough people are vaccinated, chance of germ infecting the non-immunized population is small  Can lead to disappearance of diseases (smallpox) – Vaccination no longer necessary
  • 15. Further Proof of the Effectiveness of Vaccines
  • 16. Development of Vaccines  Common misconception that activation of the immune system results in protective immunity  Multiple factors affect decisions when making vaccines 1. Activation of specific branch of immune system 2. Development of immunological memory
  • 17. Role of Memory Cells  Depends on incubation period of pathogen – Short Incubation Periods  ex. Influenza  Symptoms already under way by the time memory cells are activated  Repeated immunizations with neutralizing antibodies – Long Incubation Periods  ex. Poliovirus  Enough time to allow memory B cells to respond
  • 18. Immunological Memory vs. Serum Antibody Levels
  • 19. Types of Vaccines  Whole-Organism – Attenuated Viral/Bacterial – Inactivated Viral/Bacterial  Purified Macromolecules – Polysaccharide – Toxoid – Recombinant Antigen – Recombinant-Vector  DNA  Synthetic Peptide  Multivalent Subunit
  • 20. Whole-Organism Vaccines  Many common vaccines used consist of inactivated or attenuated bacterial cells or viral particles  Includes attenuated and inactivated vaccines
  • 21. Attenuated Viral or Bacterial Vaccines  Attenuation – to reduce in force, value, amount, or degree; weaken – Achieved by growth under abnormal culture conditions – Bacillus Calmette-Guerin (BCG) – Act as a double edged sword, as they have distinct advantages and disadvantages…
  • 22. Advantages of Attenuated Bacterial or Viral Vaccines  Advantages stem from their capacity for transient growth  Prolonged immune-system exposure  Single immunizations  Replication within host cells
  • 23. Exception to the Rule…  Sabin Polio vaccine consists of 3 attenuated strains of poliovirus  Colonization of intestine results in immunity to all 3 strains – Production of secretory IgA and induction of IgM and IgG  Result is the need for boosters – Individual strains interfere with one another  First immunization  one strain predominates in growth  Second Immunization  immunity generated by previous immunization limits growth of previously predominant strain  Third Immunization  same principle as second immunization
  • 24. Disadvantages of Attenuated Bacterial or Viral Vaccines  MAJOR disadvantage is possible reversion – ex: Rate of reversion of Sabin Polio vaccine is one case in 4 million doses  Presence of other viruses as contaminants  Unforeseen postvaccine complications
  • 25. The Future of Attenuation…  Genetic engineering techniques provide new methods of attenuation  Herpes virus vaccine for pigs  Possible elimination of reversion?
  • 26. Inactivated Viral or Bacterial Vaccines  Methods of inactivation include heat or chemical agents – End result…. Loss of replication ability  Difficult to inactivate due to potential for denaturation of epitopes – Dependence on higher order levels of protein structure
  • 28. Attenuation vs. Inactivation  Attenuation – Normally require one dosage to induce relatively permanent immunity – Primarily cell-mediated in nature – Despite reliance on cell-mediated immunity, increased IgA response  Inactivation – Requires multiple boosters – Emphasis on activating humoral immunity However, something very important is missing….
  • 29. Adjuvants  Adjuvants are CRITICAL for the use of inactivated vaccines  Most widely used are aluminum salts (mainly hydroxide or phosphate)  Effects include liberation of antigen, chemoattraction, and inflammation
  • 30. ISCOMS  Immunostimulating Complexes  Multilmeric presentation of antigen/adjuvant  Enhanced cell-mediated immune response, delayed-type hypersensitivity, cytotoxic T lymphocyte response, increased Ag expression associated with MHC II
  • 31. Additional Facts From Dr. David Satcher  Presented a more social rather than technical view of vaccines  Barriers to health care include the “7 U’s” – Uninsured, Under-issued, Under- represented, Uninspired, Untrusting, Uninformed – Ethical Variations  Significant Social Costs associated with vaccine-preventable diseases – $10 billion per year – 36,000 elderly die yearly from influenza despite availability of vaccine – Social impetus is needed to lower these figures
  • 32. Impact of Vaccines on Public Health  Between 1977 and 1980, smallpox was eradicated in the United States – Global eradication is currently a major consideration – Phenomenon of herd immunity  Measles occurrences at a record low