Vaccination and Immunity

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1 Vaccination and Immunity Eric A. Utt, PhD Director, Worldwide Science Policy Pfizer Inc California Immunization Coalition Summit 2012 Completing the Circle: Ensuring Adult & Adolescent Vaccination for All Monday, April 23, 2012

2 Vaccine preventable diseases Polio Rubella Small Pox Diphtheria Measles

3 If not for vaccines Polio Childhood and adult paralysis Rubella (German measles) - cause birth defects and mental retardation in 20,000 newborns annually. Congenital rubella syndrome (CRS) Measles - infect about 4 million children, killing 3,000 annually Diphtheria once one of the most common causes of death in school-aged children Haemophilus influenzae type b (Hib) once caused meningitis in 15,000 children, leaving many with permanent brain damage Pertussis (whooping cough) very high infant mortality.

4 What do cows have to do with vaccines? Vaccination experiment (Jenner 1796) Fluid from sore of cowpox infected woman Healthy smallpox/cowpox naïve boy Six weeks later boy challenged with smallpox Immunity to Smallpox

5 History of vaccines Salk IPV MMR HBV Hib pneumococcal conjugate Measles 1979 Smallpox eradicated 1995 Hep A, Varicella HPV for females 2010 Polio almost eradicated 2020 Goal to eradicate Measles 1. Source: History of Vaccines Timeline. Every Child by Two < >

6 Impact of Vaccines in the 20th Century United States

7 Impact of Vaccines in the 20th Century United States

8 Impact of Vaccines in the 20th Century United States

9 Impact of Vaccines in the 20 th Century

10 Immune System: Three parts 1. Physical barriers Skin Saliva Digestion, (other mechanical). 2. Non specific Inflammatory Response Pyrogenic Response (fever, chills) - Edema (swelling) - Local and generalized inflammation - White blood cell recruitment - Cytokines - Specific Immune response - T cells - B cells - Antibodies - Cytokines - Antigen processing cells - Memory cells - Phagocytic cells Source: The Immune System. National Institute of Health <

11 Origins of the Immune System: Stem Cells

12 Lymphocyte differentiation

13 Immune System Activation

14 The Battle Between Infection and Immunity Infection Immune Response Time

15 Primary and Secondary immune responses Delves et al. Roitt's Essential Immunology. 11th ed p 29 col 1, para 1, Figure 2.12, p 202 col 2, para 3, p 203 Figure 9.16 Primary Response Secondary Response Follows initial encounter with a foreign antigen - Initiates innate and acquired immune responses Characterized by: - Slow initiation of immune response (may not prevent infection) Occurs when antigen is subsequently encountered Characterized by: - Rapid initiation of innate and acquired immune responses - Greater intensity of immune response - Longer-lasting immune response - Production of copious IgG antibodies

16 Time course of Primary and Secondary immune responses Primary antigen challenge Memory cells formed Secondary antigen challenge Antibody production Primary response IgM IgG Secondary response Time On first exposure to an antigen, the immune system mounts a slow primary response. It also directs the formation of memory cells. On second exposure, those memory cells launch a faster, stronger, and longer-lasting secondary response, dominated by IgG antibodies Adapted from Delves et al. Roitt's Essential Immunology. 11th ed p 203 Figure 9.16

17 Acquired immunity Naturally Acquired Immunity Artificially Acquired Immunity Source: Applegate E (2000). The anatomy and physiology learning system (2nd ed.). Philadelphia: Saunders. Figure 16-2

18 Vaccines teach the immune system by mimicking a natural infection Prime immune system with a non-pathogenic antigen from a specific pathogen Induce a primary immune response by simulating an infection Body consequently acquires a storehouse of memory cells Secondary immune response then kicks in immediately should exposure occur Administered on a schedule: single dose or multiple (booster) doses Booster doses are required with many vaccines to achieve a sustained, predictable secondary immune response Must induce pathogen-specific immunity and be safe 2 1. Keusch et al. Immunization principles and practice. In: Kasper et al. Harrison's Principles of Internal Medicine. 16th ed Delves et al. Roitt's Essential Immunology. 11th ed

19 Vaccine Concept Infection Infection Naive Immune Cell Vaccine Effector Immune Cells Memory Immune Cells Recall Response Adaptive Immunity A vaccine pre-adapts the immune response.

20 Vaccination Effects on the Immune System

21 Major types of vaccines Type Antigenic Preparation Examples Live (attenuated) Living organisms or viruses modified to retain antigens and ability to replicate but with reduced virulence 1 In rare cases, causes clinical disease in healthy people and life-threatening disease in immunocompromised patients Polio (Sabin vaccine) Measles, mumps, rubella Inactivated (may require an adjuvant to enhance immunogenicity) Whole pathogen: Virus/bacteria cultured, then inactivated Polio (Salk vaccine) with heat or chemicals to prevent replication 1 Rabies Pathogen fraction: Inactivated pathogen further purified to retain only the antigens needed to stimulate an immune response 1 Tetanus Hepatitis B (inactivated viral antigen) Conjugated polysaccharide: Polysaccharide chemically linked to a protein to increase immunogenicity 2 Haemophilus influenzae type b conjugate Protein conjugate Recombinant subunit Antigens produced by genetic engineering 1 Hepatitis B (yeast-derived recombinant) 1. Delves et al. Roitt's Essential Immunology. 11th ed Janeway et al. Immunobiology: The Immune System in Health and Disease. 5th ed

22 Disease transmission through droplet infection

23 Disease transmission through droplet infection

24 Disrupted Disease Transmission: Indirect Immunity by Vaccination Protection of non vaccinee

25 Outbreaks today..

26 Antibiotics timeline Antibiotic Sulfonamides Lactam Aminoglycosides Cyclic Polypeptides Chloramphenicol Neomycin Tetracycline Macrolides Glycopeptide Aminoglycoside A Lactam II Year of reported cases of resistance Year introduced into clinic Lactam III lactam IV Lincosamide lactam V Piperacillin Ureidopenicllin Aztreonam Penams Quinolones Quinupristin-Dalfopristin Oxozolinodones Glycylcycline Year 26 Source: Policies and incentives for promoting innovation in antibiotic research. se2009.eu. June 21, 2010Note: Dates are estimates

27 Vaccines Timeline Small pox Rabies DPT Polio (Salk IPV) Measles MMR Antibiotic Hepatitis B H. Influenzae B Hepatitis A Varicella HPV Year of reported cases of resistance Year introduced into clinic Tigecycline Year 27 Dates are estimates

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