1. Varun U. Shetty, MD* 2. Parul Chaudhuri, MD† 3. Camille Sabella, MD‡ 1. *Department of Internal Medicine–Pediatrics 2. †Department of Internal Medicine, Case Western Reserve University–MetroHealth Medical Center, Cleveland, OH 3. ‡Center for Pediatric Infectious Diseases, Cleveland Clinic Children’s Hospital, Cleveland, OH * Abbreviations: APC: : antigen-presenting cell BCG: : bacille Calmette-Guerin CDC: : Centers for Disease Control and Prevention DC: : dendritic cell DTaP: : diphtheria-tetanus-acellular pertussis Hep B: : hepatitis B Hib: : Haemophilus influenzae type b IPV: : inactivated polio vaccine MMR: : measles-mumps-rubella OPV: : oral polio vaccine PCV13: : 13-valent pneumococcal conjugate vaccine PS: : polysaccharide Tfh: : follicular T helper cell VAPP: : vaccine-associated paralytic poliomyelitis WHO: : World Health Organization 1. Clinicians must understand the rationale for the current immunization schedule. 2. Clinicians must understand the basic immunologic responses associated with the various vaccine components. After completing this article, readers should be able to: 1. Understand the basic concepts of vaccination immunology. 2. Provide the rationale for age at first vaccine dose. 3. Provide the rationale for spacing out vaccines at 4 to 8 weeks. 4. Explain the rationale for primary series and booster combination. 5. Explain why vaccinations do not need to be started over again during catch-up. Vaccines use the knowledge of the immune system to mimic infection, generate immunologic memory, and prepare the body for future infections. An ideal vaccine provides lifelong immunity from disease and protects against multiple strains of the same disease; it is safe, inexpensive, stable, and preferably not administered via injection. (1) The main objective of the vaccination schedule is to protect individuals from disease by providing immunity before they acquire disease. (2) Long-term immunity is important in determining the effectiveness of the immunization schedule. Along with this, short-term protection, local prevalence and incidence, disease epidemiology, safety, and programmatic aspects (including number of doses, funding, organization, and cost) are important factors in determining the immunization schedule. (3)(4) Development of vaccine schedules is based on a large body of basic sciences and epidemiologic research. There is constant review of evidence, adverse events, and epidemiology by a panel of experts. To understand how vaccines provide protection, it is important to understand the essential components that compose the immune system and how the immune system generates a response to perceived pathogens. The immune system can be classified into …