Qualitative Ab Changes during 1 o and 2 o Responses Class switching 1 o Ag 2 o Ag Total Ab IgM Ab IgG Ab D a y s A f t e r I m m u n i z a t i o n A b T i t e r Cellular Events in 1 ID: 935499
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Slide1
Ab
formation
Slide2Phases of the Humoral Response
Slide3Qualitative Ab Changes during
1
o
and 2o Responses
Class switching
1
o
Ag
2
o
Ag
Total Ab
IgM Ab
IgG Ab
D a y s A f t e r I m m u n i z a t i o n
A b T i t e r
Slide4Cellular Events in 1
o
Response to
T-dependent Ags
IgM
Memory Cells
IgG
1
o
Ag
Slide5Cellular Events in 2
o
Response to
T-dependent Ags
IgM
Memory Cells
IgG
IgG
Memory Cells
Memory Pool
Naive B cell
Slide6Kinetics of Ab Response to
T-independent Ags
4 Phases
IgM antibody
No secondary response
1
o
Ag
2
o Ag
D a y s A f t e r I m m u n i z a t i o nA b T i t e r
IgM Ab
Slide7Cumulative Primary and Secondary Responses
Slide8Immunization
Slide9Immunity
Protection against disease (often infectious).
In response to foreign substances.
Mediated by cells, tissues, and/or products of cells and tissues.
Slide10Vaccination/Immunization
The fundamental principle is to administer a killed or attenuated form of an infectious agent or a component of an infectious agent that does not cause disease but elicits an immune response that provides protection against infection by the live, pathogenic agent.
Attenuated
: weakened or avirulent
Slide11Milestones in Immunization
Variolation
Egyptian markings (~3000 BC)
China (~2000 BC)
England and later US (~1700 AD)Edward JennerDiscovers smallpox vaccine (1796)Louis PasteurDiscovers rabies vaccine (1885)
Slide12Modern Era of the Vaccine
Diptheria and Tetanus (1920s)
Pertussis (1934)
Polio
Salk (1955)SabinMeasles, mumps, and rubella (1960s)
Slide13Vaccine Benefits
Protection or Immunity
Reduced exposure
Disease prevention
IndividualCommunityHerd immunityCost
Slide14Vaccine Considerations
Safety
Immunogenicity
Type of protection
TimequicknesslongevityRoute of administrationMagnitudeAntigenic variationTarget populationStorage Cost Most vaccines in current use work by inducing humoral immunity.
Slide15Passive Immunity
Natural
Placental transfer of IgG
Colostral transfer of IgA
Artificial Antibodies → human or horseImmune cells
Slide16Advantages
Disadvantages
immediate protection
no long term protection
no memory
serum sickness
risk of hepatitis and AIDS
alloreactive
responses
Advantages and Disadvantages of Passive Immunization
Slide17Infection/Condition
Indication
Antibody Source
Passive Immunization
Vericella zoster
human
immunodeficiencies
Gas gangrene, botulism, snake bite, scorpion sting
horse
post-exposure
Rabies
human
post-exposure
Hypogamma-globulinemia
human
prophylaxis
Slide18Relationships Between Active and Passive Immunity
Slide19Active Immunization
Natural
Artificial
Exposure to sub-clinical infections
Live, attenuated organisms
Inactivated /killed organisms
Subunit
Conjugate
Toxoids
DNA Vaccines
Recombinant vectors
Slide20Live Attenuated Vaccines
Treat such that they no longer cause disease.
Mechanisms of attenuation
Repeated passage
Temperature-sensitive mutationsDeletion mutants
Nutritional auxotrophs
Slide21Live Attenuated Vaccines
Slide22M. bovis
BCG
*not used in this country
Polio
*
not used in std. schedule
Measles, mumps & rubella
Yellow fever
*military and travelers
Varicella zoster
Hepatitis A
*standard 2006Live Attenuated Vaccine Examples
Influenza*selected age group (5-49)
Slide23Live Attenuated Vaccines
Treat such that they no longer cause disease.
Mechanisms of attenuation
Advantages
Typically elicit the innate and adaptive immune responses the pathogen would.Long lasting immunity.
Disadvantages/ConcernsSafetyImmunocompromised
Reversion Genetic plasticity
Slide24Inactivated (Killed) Whole-Organism Vaccines
Treat such that they are no longer viable.
Mechanisms of inactivation
Chemical
Heat Radiation AdvantagesAlleviates many concerns with live, attenuated.Organism remains intact.Disadvantages/ConcernsToxicity Limited success with some examples.
Slide25Polio
Influenza
*elderly and at risk
Typhoid, cholera, plague
*epidemics and travelers
Rabies
*post exposure
Pertussis
*replaced by the acellular vaccine
Inactivated (Killed) Whole-Organism Vaccines
Q fever
*population at risk
Slide26Microbial Subunit Vaccines
Purified antigens
Surface proteins
Surface polysaccharides
Polysaccharide-conjugateToxoidModes of purification
Slide27Microbial Subunit Vaccines
Slide28Microbial Subunit Vaccines
Protein Examples
Lyme disease - OspA
Pertussis – virulence factor proteins
Hepatitis B – HBsAgHuman papilloma virus – immunodominant proteinsCholera – toxin subunits
Slide29Microbial Subunit Vaccines
Polysaccharide & Conjugate Examples
Streptococcus pneumoniae
–polysaccharide mixture
Streptococcus pneumoniae – protein conjugated polysaccharideNeisseria meningitidis – protein conjugated polysaccharideHaemophilus influenzae – protein conjugated polysaccharide
Slide30Modification of Toxin to Toxoid
Toxin
Toxoid
Chemical or genetic modification
Slide31Microbial Subunit Vaccines
Toxoid Examples
Tetanus
Diptheria
Pertussis
Slide32Microbial Subunit Vaccines
Advantages
Tailor the response to immunodominant antigens
Focus on toxic components
DisadvantagesReduced immunogenicity
Slide33DNA Vaccines
Advantages
Safe
Selection of immunodominant antigens
Adjuvant properties – unmethylated nucleotides (CpG –TLR9)
Co-expression of cytokines
Disadvantages
Limited effectiveness in clinical trials
Slide34Recombinant Vectors
Introduce genes encoding microbial antigens into non-pathogenic viruses or bacteria.
Vaccinia virus, adenovirus
Attenuated
Salmonella sp
.
Slide35Recombinant Vectors
Advantages
Selection of immunodominant antigens
Induce the full complement of immune responses.
Induce strong CTL responsesDisadvantagesSafety concernsImmunocompromisedOncogenesInduce strong CTL responses
Slide36Adjuvants
Salts:
Al(OH)3; AlPO4;
Yes
Human use
Mode of action
Slow release of antigen; TLR interaction and cytokine induction
Adjuvant type
Slow release of antigen
No
Mineral oils
Substances that when cointroduced with antigen, enhance the immunogenicity.
Slide37Adjuvants
Human use
Mode of action
Adjuvant type
Synthetic polymers:
Liposomes
ISCOM
Poly-lactate
Facilitate antigen uptake, transport, and presentation
No
Yes
Bacteria:
Bordetella pertussis
Mycobacterium bovis BCG and others
No
TLR interaction and cytokine induction
Bacterial products:
Myramyl peptides
No
TLR interaction and cytokine induction
Slide38Adjuvants
Poly-nucleotides:
CpG
No*
Human use
Mode of action
TLR interaction and cytokine induction
Adjuvant type
Cytokines:
IL-1, IL-2, IL-12, IFN-
γ
,
etc.
No*
Promote cell-mediated immunity
*Used in experimental clinical trials