2. Ab formation

3. Hallmarks of the Immune Response Self/Non-self Discrimination Memory Specificity

4. Fate of the Immunogen Clearance after 1 o exposure –Equilibrium phase –Catabolic decay phase –Immune elimination phase Clearance after 2 o exposure – More rapid onset of immune elimination phase Immune Elimination Phase Days after Injection 2 4 6 8 1210 Amount of Circulating Ag (%) 25 75 100 50 Equilibrium Phase Catabolic Decay Phase

5. Kinetics of the Ab Response T-dependent Ag; 1 o Response Lag phase Log phase Plateau phase Decline phase Ag 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 LAG LOGDECLINEPLATEAU

6. Kinetics of the Ab Response T-dependent Ag; 2 o Response * Specificity Lag phase Log phase Plateau phase Decline phase 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 n A b T i t e r

7. Qualitative Ab Changes during 1 o and 2 o Responses Class variation – 1 o - IgM – 2 o - IgG, IgA or IgE 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

8. Qualitative Ab Changes during 1 o and 2 o Responses Class variation Affinity – Affinity Maturation 1 o Ag D a y s A f t e r I m m u n i z a t i o n A f f I n I t y 2 o Ag IgG Ab IgM Ab High Dose Low Dose

9. Qualitative Ab Changes during 1 o and 2 o Responses Class variation Affinity – Clonal selection – Somatic mutation 10 10 10 8 10 6 10 5 10 9 10 7 High Ag Concentration 10 10 10 8 10 6 10 5 10 9 10 7 Low Ag Concentration Moderate Affinity Ab High Affinity Ab

10. Qualitative Ab Changes during 1 o and 2 o Responses Class variation Affinity Avidity Cross reactivity

11. Cellular Events in 1 o Response to T-dependent Ags Lag –Clonal selection Log –IgM –Class switching Stationary Decline Memory Cell Pool IgM Memory Cells IgG 1 o Ag

12. Cellular Events in 2 o Response to T-dependent Ags Lag phase –Virgin cells –Memory cells Log phase –Pool size –IgG, IgA or IgE Stationary Decline –Sustained production IgM Memory Cells IgG Memory Cells Memory Pool Virgin B cell

13. Memory T cells Th Memory Cells Th Memory Cells Memory Pool Virgin cell T Cells –Virgin cells –Memory cells Th cells –Cytokines Long Term Memory

14. Kinetics 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 n A b T i t e r IgM Ab

15. Class Switching DNA rearrangement –Antigen dependent –Switch site –Same VDJ –T H cytokines

16. Membrane vs Secreted Ig Differential pre-mRNA processing –Membrane exons –Alternate polyA sites –Same VDJ region used mRNA Primary Transcript H3H4 M M H3 H4 M M AAAA Membrane Bound H3H4 AAAA Secreted H3H4 AAAA H3H4 M M AAAA DNA Polyadenylation Sites

18. 17 Milestones in immunization u 1500BC u Turks introduce variolation u 3000BC u Evidence of sniffing powdered small pox crust in Egypt u 2000BC u Sniffing of small pox crust in China u 1700AD u Introduction of variolation in England and later in the US

19. 18 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. 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. Introduction of variolation

20. 19 Milestones in immunization u 1780AD u Edward Jenner discovers small pox vaccine

21. 20 Edward Jenner Discovery of small pox vaccine

22. 21 Edward Jenner Among patients awaiting small pox vaccination

23. 22 1920s Diphtheria and Tetanus 1934 Pertussis 1955 Salk polio Modern era of the vaccine 1885 Rabies vaccine (Pasteur)

24. 23 1960s Mumps measles and rubella virus Sabin polio 1990s Hepatitis and varicella 1985 Haemophilus Modern era of the vaccine  2000 Human Papillomavirus (HPV)

25. 24 Pre- & post-vaccine incidence of common preventable diseases

26. 25 Different modes of acquiring immunity Natural resistance Artificial Natural Passive Artificial Natural Active Immunity Acquired

27. 26 NaturalArtificial Colostral transfer of IgA Placental transfer of IgG Antibodies or immunoglobulins Immune cells Passive Immunity

28. 27 disease indication antibody source Passive Immunization human, horsediphtheria, tetanusprophylaxis, therapy vericella zoster human immunodeficiencies gas gangrene, botulism, snake bite, scorpion sting horse post-exposure rabies, human post-exposure hypogamma- globulinemia human prophylaxis

29. 28 Advantages Disadvantages serum sickness immediate protection no long term protection graft vs. host disease (cell graft only) risk of hepatitis and Aids Advantages and Disadvantages of Passive Immunization

30. 29 Active Immunization Natural Artificial exposure to sub- clinical infections Attenuated organisms killed organisms sub- cellular fragments toxins others

31. 30 tuberculosis not used in this country polio* not used in std. schedule measles, mumps & rubella yellow fever Military and travelers Varicella zoster children with no history of chicken pox hepatitis A standard 2006 Live Attenuated Vaccines Influenza selected age group (5-49)

32. 31 polio influenza elderly and at risk typhoid, cholera, plague epidemics and travelers rabies post exposure pertussis replaced by the acellular vaccine Killed Whole-Organism Vaccines Q fever population at risk

33. 32 Microbial Fragment Vaccines Bordetella. Pertussis virulence factor protein Haemophilus influenzae B protein conjugated polysaccharide Streptococcus pneumoniae Polysaccharide mixture Neisseria meningitidis polysaccharide

34. 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

35. 34 Modification of Toxin to Toxoid toxin moiety antigenic determinants chemical modification ToxinToxoid

36. 35 anti-Idiotype Vaccine Immuno-dominant peptide Future Vaccines DNA

37. 36 anti-Idiotype Vaccine

38. 37 Antiidiotype antibody in tolerance Antiidiotype antibody production Antiidiotype mediated tolerance

39. 38 Adjuvants Salts: Al(OH)3; AlPO4; CaPO4 Be(OH)2 Yes No Human useMode of action Slow release of antigen; TLR interaction and cytokine induction Adjuvant type Slow release of antigenNo Mineral oils without bacteria Yes Bacteria in Mineral oils (Mycobacteria, Nocardia) No Slow release of antigen TLR interaction and cytokine induction

40. 39 Adjuvants Human useMode of actionAdjuvant type Synthetic polymers: Liposomes ISCOM Poly-lactate Slow release of antigenNo 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

41. 40 Adjuvants Poly-nucleotides: CpG No* Human useMode of action TLR interaction and cytokine induction Adjuvant type Cytokines: IL-1, IL-2, IL-12, IFN-γ, etc. No* Activation of T and B cells and APC *Used in experimental immunotherapy of human malignancies

42. 41 Recommended Childhood Immunization Schedule MMWR, 55: Jan 5, 2007 Recommended age rangeCatch-up immunizationCertainigh risk groups

43. 42 Recommended Immunization Schedule for Ages 7-18 MMWR, 55: Jan 5, 2007 Recommended age rangeCatch-up immunizationCertain high risk groups

44. 43 Recommended Immunization Schedule for Ages 7-18 MMWR, 55: Jan 5, 2007 Recommended age rangeCatch-up immunizationCertain high risk groups

45. 44 Adverse Events Occurring Within 48 Hours DTP of Vaccination Event Frequency local redness, swelling, pain 1 in 2-3 doses systemic: Mild/moderate fever, drowsiness, fretfulness vomiting anorexia 1 in 2-3 doses 1 in 5-15 doses systemic: more serious persistent crying, fever collapse, convulsions acute encephalopathy permanent neurological deficit 1 in 100-300 doses 1 in 1750 doses 1 in 100,000 doses 1 in 300,000 doses