Chapter 16 Immunizations and Immunity

Amazing Fact “An estimated 2.1 million people around the world died in 2002 of diseases preventable by widely used vaccines. 1 With an investment of 3 billion USD a year, every child in the developing world could receive complete immunization coverage. 2 1 World Health Organization. Immunization Against Diseases of Public Health Importance. March 2005.) 2 UNICEF. Immunize Every Child: GAVI Strategy for Immunization Services. February 2000)

History Edward Jenner –Cowpox and smallpox experiments Louis Pasteur –Cholera work –Originator of term “vaccine”

Mechanisms of Immunity Innate immune system –Present from birth –Does not differentiate challenge Adaptive immune system –Synonyms: acquired or specific immunity –Responds to specific challenges

Innate Immunity Nonspecific response –Anatomic barriers Skin and mucosal membranes –Physiologic barriers Acidity and chemical mediators –Phagocytosis Neutrophils and macrophages –Inflammation Antibacterial and stimulatory effects –Natural killer cells Tumor cytotoxicity

Figure 1: Phagocytosis

Adaptive Immunity Responds to specific antigenic challenge –Cells involved T lymphocytes (T cells) B lymphocytes (B cells) Types of adaptive responses –Cell-mediated (cellular) immunity –Humoral immunity

Cell-mediated Immunity Involves T lymphocytes –Derived from cells in the bone marrow –Mature and differentiate in the thymus –Help eliminate intracellular organisms –Present protein antigens to B cells –Secrete cytokines –Develop specific functions after antigenic exposure

Lymphocytic stem cell T lymphocyte B lymphocyte Antigen Memory cell Cytotoxic cell Helper cell Suppressor cell Antibody producing cell Memory cell Figure 2: Functional lymphoid populations following antigenic stimulation

Humoral Immunity Involves B lymphocytes –Primary defense against extracellular organisms –Recognize antigenic determinants (epitopes) leading to antibody production by plasma cells –Antibodies produced IgM, IgG, IgA, IgD, IgE

Humoral Immunity Chief functions of antibodies –Neutralize bacterial toxins –Neutralize viruses –Promote phagocytosis –Activate inflammatory response Antibodies at work –Primary and secondary responses

Antibody Titer Time 1 st exposure to antigen 2 nd exposure to antigen Figure 3: Primary and secondary response curves

Active and Passive Immunity Active immunity –Immunocompetent individual produces immune products after exposure to foreign organism Immune products: antibodies, memory cells –May be naturally developed (natural infection) or artificially acquired (vaccine)

Active and Passive Immunity Passive immunity –Involves transfer of preformed antibodies –May involve natural acquisition (maternal- fetal transfer) or may be acquired (injection of immunoglobulin)

Active and Passive Immunity Differences in protection –Active immunity Long-term protection due to production of memory cells –Passive immunity Short-term protection due to lack of memory cell production

Vaccines Mimic natural infection Stimulate the immune system Key requirements for success –Immunologic memory –Specificity

Vaccines Goal –Stimulate memory T and B cells To induce specific immunity Eliminate organisms Neutralize bacterial toxins

Vaccines Live, attenuated vaccine –Contains weakened (attenuated) form of live organisms –Advantage: produces strong cellular and humoral responses –Disadvantages: chance organism may become virulent again requires refrigeration

Vaccines Inactivated vaccines –Killed organisms –Advantages: Safer and more stable than live vaccines Usually do not require refrigeration Some may be freeze-dried –Disadvantage: May stimulate weaker response than live vaccines

Vaccines Toxoid vaccines –Treated microbial toxins –Advantage: Stimulate strong antibody responses that eliminate harmful toxins

Vaccines Subunit vaccines –Composed of selected microbial epitopes –Often administered with adjuvants such as aluminum salts –Advantages: Greater specificity Adverse reactions less likely

Vaccines Conjugate vaccines –Couple polysaccharide antigens to protein carrier –Advantage: Better recognition by the immune system to stimulate strong immune response especially in infants and children

Table 3: Types of Vaccines Vaccine Type Examples of Vaccines Live, attenuated vaccine Measles, mumps, rubella, polio (Sabin) vaccine, varicella Inactivated (killed) vaccine Cholera, rabies, influenza, hepatitis A, polio (Salk) vaccine Toxoid vaccine Tetanus, diphtheria Subunit vaccine Hepatitis B, pertussis, pneumococcus (Streptococcus pneumoniae) Conjugate vaccine Haemophilus influenzae type B, pneumococcus (Streptococcus pneumoniae)

Future Vaccines DNA vaccines –Use organism’s genes to invoke antigen expression in host Recombinant vector vaccines –Use attenuated organism to introduce organism’s DNA into host Hurdles to vaccine development –Mutation of organisms especially viruses –Genetic complexity of certain organisms

Immunization of Selected Groups Childhood immunizations –Recommendations approved yearly by Centers for Disease Control and Prevention (CDC) American Academy of Pediatrics American Academy of Family Physicians

Immunization Schedule

Immunization of Selected Groups Adult immunizations –Influenza –Pneumococcal Travelers –Depends on site of travel Workers exposed to biological agents in work environment –Anthrax –Smallpox

Effectiveness of Vaccines Generally effective in most populations Poor-responders –Small group of individuals –Herd (community) immunity Immunity developed by group of vaccinated individuals Impediments to achieving herd immunity –Concerns regarding adverse side effects –Costs of vaccines

Barriers to Widespread Coverage Developed world –Access and cost issues among certain populations –Language barriers –Failure to obtain booster shots or complete series –Fears concerning vaccination –Underestimation of disease risk

Barriers to Widespread Coverage Developing Countries –Logistical issues Storage requirements Poor infrastructure Lack of roads –Personnel issues Shortage of health care workers