USMLE® Step 2 style questions USMLE
A 15-year-old boy comes to the office for a wellness check prior to beginning high school. He currently feels healthy and has no known allergies. His most recent immunization was for MCV-4 (meningococcal) two years ago, and his last immunization for tetanus was 10 years ago. Based on the patient's immunization history, which of the following vaccinations would be most appropriate to give at this time?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS, Will Wei, Jake Ryan, Elizabeth Nixon-Shapiro, MSMI, Kara Lukasiewicz, PhD, MScBMC
When you get an infection, you develop adaptive immunity.
In other words, you generate memory T and B cells, so that if you encounter the same antigen again, they can quickly replicate and respond.
Most of the time we think of immunologic memory developing after natural infection. But memory T and B cells also develop after vaccination.
Vaccination is the process of generating a protective adaptive immune responses against microbes by exposure to nonpathogenic forms or components of microbes.
That’s the key - getting long term active protection to a harmful microbe, from something that’s not harmful.
Vaccination also helps up to establish herd immunity.
Herd immunity is the concept that if enough people in the population - or herd - are vaccinated the entire population, even those who are unvaccinated, develop a higher resistance to that infection.
The amount of people within a herd that need to be vaccinated to maintain herd immune status differs from pathogen to pathogen.
When too few people in a herd are vaccinated, there are more people in the population that are able to get the illness and spread it.
Vaccination is an active process of developing immunity.
This is different from passive immunity which is where a person gets antibodies that are made by another person or animal like a horse or mouse or by cells in a lab.
A common form of this is when antibodies are pooled from the community and is given intravenously - it’s called intravenous immunoglobulin or IV-Ig.
Passive immunity last for only as long as the antibodies last - usually weeks to months.
The antibodies that an infant receives from their mother in utero or during breastfeeding are examples of passive immunity.
IgG antibodies in the blood cross the placenta initially protecting the baby to some pathogens that mom has already made antibodies to.
These IgG maternal antibodies will be degraded around six months of age.
IgA antibodies are plentiful in breast milk and are passed to the baby during nursing, these antibodies provide protection from pathogens that may be found at mucosal sites.
Once a baby weans off of breastmilk, these antibodies are no longer passed and the ones that have already entered the baby slowly degrade over the course of a few months. Fortunately, by that point the baby will begin to make some of their own antibodies.
Vaccines can be administered four ways: intramuscularly, intradermally, subcutaneously or subQ, or orally.
Typically, a vaccine is considered successful if it results in a strong antigen specific antibody titer, meaning in most recipients a strong antibody response is made to the vaccine.
When a patient receives a vaccine, CD4+ helper T cells are activated and produce cytokines like IFN gamma, TNF alpha, and IL-2 to promote growth of immune cells and class switching of activated B cells.
Once activated B cells will differentiate into plasma cells capable of producing IgG, IgA, or IgE antibodies.
The exact antibody response depends on the route and type of vaccine.
For example, most intramuscular vaccinations lead to IgG production while the rotavirus vaccine, which is given orally, leads to IgA production.
There are four main types of vaccines: Live attenuated, inactivated, subunit, and toxoid vaccines.
Live attenuated and inactivated vaccines are whole cell vaccines, which means that the whole virus or bacteria is used to create the vaccine. Subunit vaccines - which includes polysaccharide vaccines, and Toxoid are considered fractionated vaccines because only one part of the pathogen is used to create the vaccine.
Live vaccines are attenuated, meaning that the pathogen has been weakened in the laboratory to make it less pathogenic, but still able to replicate in the vaccinated person so that it can stimulate an immune response.
In fact, the immune response to a live attenuated vaccine is almost identical to what happens in a natural infection.
Inactivated vaccines use a pathogen that has been killed using heat or chemical fixation with formalin.
The immune response is mostly humoral or antibody mediated and with little to no cellular immunity, meaning mostly plasma cells making antibodies, and not T cells.
As a result, the immune response generated by inactivated vaccines is not as strong as that from natural infection or from a live vaccine.
For this reason, as immunity wanes over time patients may require “booster shots” or additional vaccination to boost the memory response.
Subunit vaccines that contain just the portions of pathogens that our bodies response to - like polysaccharides or proteins.
Often proteins from several different pathogens are conjugated or attached together to form conjugate subunit vaccines.