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Immunology
1.
2. A Quick GlimpseâŚ
ď§ Active vs. Passive Immunization
ď§ Designing Vaccines
ď§ Whole-Organism Vaccines
ď§ Purified Macromolecules as Vaccines
ď§ Recombinant-Vector Vaccines
ď§ DNA Vaccines
ď§ Synthetic-Peptide Vaccines
ď§ Mulvivalent Subunit Vaccines
3. Two Types of Immunization
ď§ Passive Immunization
â Methods of acquisition include natural maternal antibodies,
antitoxins, and immune globulins
â Protection transferred from another person or animal
ď§ Active Immunization
â Methods of acquisition include natural infection, vaccines (many
types), and toxoids
â Relatively permanent
5. Passive Immunization
ď§ Can occur naturally via transfer of maternal antibodies across placenta to
fetus
ď§ Injection with preformed antibodies
â Human or animal antibodies can be used
â Injection of animal Abâs prevalent before vaccines
ď§ 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
8. The Immune System and Passive
Immunization
ď§ The transfer of antibodies will not trigger the immune system
ď§ There is NO presence of memory cells
ď§ Risks are included
ď§ Recognition of the immunoglobulin epitope by self immunoglobluin paratopes
ď§ Some individuals produce IgE molecules specific for passive antibody, leading
to mast cell degranulation
ď§ Some individuals produce IgG or IgM molecules specific for passive antibody,
leading to hypersensitive reactions
9. Active Immunization
ď§ Natural Infection with
microorganism or artificial
acquisition (vaccine)
ď§ Both stimulate the proliferation of T
and B cells, resulting in the
formation of effector and memory
cells
ď§ The formation of memory cells is
the basis for the relatively
permanent effects of vaccinations
10. Principles Underlying Vaccination
ď§ Concept of Immunity
â Self vs. Non-self
â Antigen specificity
â Indicated by presence of effector cells
â Protection from infectious diseases using above
methods
12. Effectiveness of Vaccinations
ď§ Small percentage of recipients will respond poorly
â Role of genetic determinants
ď§ Herd Immunity
â Majority of population is immune, so chance of susceptible individual
contacting infected individual is low
â Measles Epidemic
13. Herd Immunity
ď§ Factors affecting herd immunity
â Environmental Factors: crowded conditions, seasonal variations
â Strength of Individualâs Immune System
â Infectiousness of Disease: greater the risk of infection, the higher
percentage of people need vaccines to attain herd immunity
ď§ When enough people are vaccinated, chance of germ infecting the
non-immunized population is small
ď§ Can lead to disappearance of diseases (smallpox)
â Vaccination no longer necessary
16. Development of Vaccines
ď§ Common misconception that
activation of the immune system results
in protective immunity
ď§ 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
ď§ Depends on incubation period of pathogen
â Short Incubation Periods
ď§ ex. Influenza
ď§ Symptoms already under way by the time memory cells are
activated
ď§ Repeated immunizations with neutralizing antibodies
â Long Incubation Periods
ď§ ex. Poliovirus
ď§ Enough time to allow memory B cells to respond
20. Whole-Organism Vaccines
ď§ Many common vaccines used
consist of inactivated or attenuated
bacterial cells or viral particles
ď§ Includes attenuated and inactivated
vaccines
21. Attenuated Viral or Bacterial
Vaccines
ď§ Attenuation â to reduce in force, value, amount, or degree; weaken
â Achieved by growth under abnormal culture conditions
â Bacillus Calmette-Guerin (BCG)
â Act as a double edged sword, as they have distinct advantages and
disadvantagesâŚ
22. Advantages of Attenuated Bacterial
or Viral Vaccines
ď§ Advantages stem from their capacity for transient growth
ď§ Prolonged immune-system exposure
ď§ Single immunizations
ď§ Replication within host cells
23. Exception to the RuleâŚ
ď§ Sabin Polio vaccine consists of 3 attenuated strains of poliovirus
ď§ Colonization of intestine results in immunity to all 3 strains
â Production of secretory IgA and induction of IgM and IgG
ď§ Result is the need for boosters
â Individual strains interfere with one another
ď§ First immunization ď one strain predominates in growth
ď§ Second Immunization ď immunity generated by previous
immunization limits growth of previously predominant strain
ď§ Third Immunization ď same principle as second immunization
24. Disadvantages of Attenuated
Bacterial or Viral Vaccines
ď§ MAJOR disadvantage is possible reversion
â ex: Rate of reversion of Sabin Polio vaccine is one case in 4 million doses
ď§ Presence of other viruses as contaminants
ď§ Unforeseen postvaccine complications
25. The Future of AttenuationâŚ
ď§ Genetic engineering techniques provide new methods of attenuation
ď§ Herpes virus vaccine for pigs
ď§ Possible elimination of reversion?
26. Inactivated Viral or Bacterial
Vaccines
ď§ Methods of inactivation include heat or chemical agents
â End resultâŚ. Loss of replication ability
ď§ Difficult to inactivate due to potential for denaturation of epitopes
â Dependence on higher order levels of protein structure
28. Attenuation vs. Inactivation
ď§ Attenuation
â Normally require one dosage to induce relatively permanent immunity
â Primarily cell-mediated in nature
â Despite reliance on cell-mediated immunity, increased IgA response
ď§ Inactivation
â Requires multiple boosters
â Emphasis on activating humoral immunity
However, something very important is missingâŚ.
29. Adjuvants
ď§ Adjuvants are CRITICAL for the use of inactivated vaccines
ď§ Most widely used are aluminum salts (mainly hydroxide or
phosphate)
ď§ Effects include liberation of antigen, chemoattraction, and
inflammation
30. ISCOMS
ď§ Immunostimulating Complexes
ď§ Multilmeric presentation of antigen/adjuvant
ď§ 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
ď§ Presented a more social rather than
technical view of vaccines
ď§ Barriers to health care include the â7
Uâsâ
â Uninsured, Under-issued, Under-
represented, Uninspired, Untrusting,
Uninformed
â Ethical Variations
ď§ Significant Social Costs associated with
vaccine-preventable diseases
â $10 billion per year
â 36,000 elderly die yearly from influenza
despite availability of vaccine
â Social impetus is needed to lower these
figures
32. Impact of Vaccines on Public Health
ď§ Between 1977 and 1980, smallpox was eradicated in the United
States
â Global eradication is currently a major consideration
â Phenomenon of herd immunity
ď§ Measles occurrences at a record low