Ab formation

1
Ab formation
2
Hallmarks of the Immune Response

• Self/Non-self Discrimination
• Memory
• Specificity

3
Fate of the Immunogen

• Clearance after 1o exposure
• Equilibrium phase
• Catabolic decay phase
• Immune elimination phase

• Clearance after 2o exposure
• More rapid onset of immune elimination phase

4
Kinetics of the Ab ResponseT-dependent Ag 1o
Response

• Lag phase

• Log phase

• Plateau phase

• Decline phase

5
Kinetics of the Ab ResponseT-dependent Ag 2o
Response

• Lag phase

• Log phase

• Plateau phase

• Decline phase

Specificity
6
Qualitative Ab Changes during 1o and 2o Responses

• Class variation
• 1o - IgM
• 2o - IgG, IgA or IgE

7
Qualitative Ab Changes during 1o and 2o Responses

• Class variation

• Affinity
• Affinity Maturation

8
Qualitative Ab Changes during 1o and 2o Responses

• Class variation

• Affinity
• Clonal selection
• Somatic mutation

9
Qualitative Ab Changes during 1o and 2o Responses

• Class variation

• Affinity

• Avidity

• Cross reactivity

10
Cellular Events in 1o Response to T-dependent Ags

• Lag
• Clonal selection
• Log
• IgM
• Class switching
• Stationary
• Decline
• Memory Cell Pool

11
Cellular Events in 2o Response to T-dependent Ags

• Lag phase
• Virgin cells
• Memory cells
• Log phase
• Pool size
• IgG, IgA or IgE
• Stationary
• Decline
• Sustained production

12
Memory T cells

• T Cells
• Virgin cells
• Memory cells
• Th cells
• Cytokines
• Long Term Memory

13
Kinetics of Ab Response toT-independent Ags

• 4 Phases
• IgM antibody
• No secondary response

14
Class Switching

• DNA rearrangement
• Antigen dependent
• Switch site
• Same VDJ
• TH cytokines

15
Membrane vs Secreted Ig

• Differential pre-mRNA processing
• Membrane exons
• Alternate polyA sites
• Same VDJ region used

16
Immunization
17
Milestones in immunization

• 1500BC
• Turks introduce variolation

• 3000BC
• Evidence of sniffing powdered small pox crust in
  Egypt

• 1700AD
• Introduction of variolation in England and later
  in the US

• 2000BC
• Sniffing of small pox crust in China

18
Introduction of variolation

• The wife of the British Ambassador in
• Turkey, in March 1717 wrote, following
• the variolation of her son, to a friend in
• England The small pox, so fatal, so general
• amongst us, is entirely harmless here
• by the invention of ingrafting.I am
• patriot enough to bring this invention into
• fashion in England.

19
Milestones in immunization

• 1780AD
• Edward Jenner discovers small pox vaccine

20
Edward Jenner
Discovery of small pox vaccine
21
Edward JennerAmong patients awaiting small pox
vaccination
22
Modern era of the vaccine

• 1934
• Pertussis

• 1885
• Rabies vaccine (Pasteur)

• 1955
• Salk polio

• 1920s
• Diphtheria and Tetanus

23
Modern era of the vaccine

• 1960s
• Mumps measles and rubella virus
• Sabin polio

• 1985
• Haemophilus

• 1990s
• Hepatitis and varicella

• 2000
• Human Papillomavirus
• (HPV)

24
Pre- post-vaccine incidence of common
preventable diseases
25
Different modes of acquiring immunity
Immunity
26
Passive Immunity

• Placental transfer of IgG

• Antibodies or immunoglobulins

• Colostral transfer of IgA

• Immune cells

27
Passive Immunization
28
Advantages and Disadvantages of Passive
Immunization

• no long term protection

• serum sickness

• immediate protection

• risk of hepatitis and Aids

• graft vs. host disease (cell graft only)

29
Active Immunization

• Attenuated organisms

• killed organisms

• exposure to sub-clinical infections

• sub-cellular fragments

• toxins

• others

30
Live Attenuated Vaccines

• polio
• not used in std. schedule

• hepatitis A
• standard 2006

• measles, mumps rubella

• yellow fever
• Military and travelers

• Varicella zoster
• children with no history of chicken pox

• Influenza
• selected age group (5-49)

• tuberculosis
• not used in this country

31
Killed Whole-Organism Vaccines

• polio

• Q fever
• population at risk

• influenza
• elderly and at risk

• typhoid, cholera, plague
• epidemics and travelers

• pertussis
• replaced by the acellular vaccine

• rabies
• post exposure

32
Microbial Fragment Vaccines

• Bordetella. Pertussis
• virulence factor protein

• Haemophilus influenzae B
• protein conjugated polysaccharide

• Streptococcus pneumoniae
• Polysaccharide mixture

• Neisseria meningitidis
• polysaccharide

33
Microbial Fragment Vaccines

• Clostridium tetani (tetanus)
• inactivated toxin (toxoid)

• Corynebacterium diphtheriae
• inactivated toxin (toxoid)

• Vibrio cholerae
• toxin subunits

• Hepatitis B virus
• cloned in yeast

34
Modification of Toxin to Toxoid
Toxin
35
Future Vaccines

• anti-Idiotype Vaccine

• DNA

• Immuno-dominant peptide

36
anti-Idiotype Vaccine
37
Antiidiotype antibody in tolerance
Antiidiotype antibody production
Antiidiotype mediated tolerance
38
Adjuvants
Human use
Mode of action
Adjuvant type

• Salts
• Al(OH)3 AlPO4 CaPO4
• Be(OH)2

Yes Yes No
Slow release of antigen TLR interaction and
cytokine induction

• Mineral oils without bacteria

Slow release of antigen
No

• Bacteria in Mineral oils (Mycobacteria, Nocardia)

Slow release of antigen TLR interaction and
cytokine induction
Yes
No
39
Adjuvants
Human use
Mode of action
Adjuvant type

• Bacteria
• Bordetella pertussis
• Mycobacterium bovis
• (BCG and others)

Yes
TLR interaction and cytokine induction
No

• Bacterial products
• Myramyl peptides

TLR interaction and cytokine induction
No

• Synthetic polymers
• Liposomes
• ISCOM
• Poly-lactate

Slow release of antigen
No
40
Adjuvants
Human use
Mode of action
Adjuvant type

• Poly-nucleotides
• CpG

TLR interaction and cytokine induction
No

• Cytokines
• IL-1, IL-2, IL-12, IFN-?, etc.

Activation of T and B cells and APC
No
Used in experimental immunotherapy of human
malignancies
41
Recommended Childhood Immunization Schedule
Recommended age range
Catch-up immunization
Certainigh risk groups
MMWR, 55 Jan 5, 2007
42
Recommended Immunization Schedule for Ages 7-18
Recommended age range
Catch-up immunization
Certain high risk groups
MMWR, 55 Jan 5, 2007
43
Recommended Immunization Schedule for Ages 7-18
Recommended age range
Catch-up immunization
Certain high risk groups
MMWR, 55 Jan 5, 2007
44
Adverse Events OccurringWithin 48 Hours DTP of
Vaccination