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Question:

A 4-year-old girl is brought to the clinic for her routine yearly visit.  She has no chronic medical conditions and has received all previously recommended vaccinations.  The patient is due to receive several vaccinations today including a second measles vaccine.  Which of the following IgM and IgG trends is expected to occur after initial and subsequent measles vaccinations?

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Explanation:

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Although B cells are the primary players in inducing a vaccine response, T cells play a key role in enabling high-affinity antibodies and immunological memory.  Most vaccinations use peptide antigens or nonpeptides bonded to peptides (ie, conjugate vaccine) so the antigen can be displayed on MHC class II molecules on antigen-presenting cells (APCs), which leads to a much stronger T-cell–mediated immune response.

Vaccines given in series (eg, measles, mumps, and rubella) typically trigger the following immunologic changes:

  • Primary response:  Upon initial vaccination, foreign antigen binds to and activates B lymphocytes with compatible antigen receptors, leading to clonal B-cell expansion and differentiation into short-lived plasma cells that secrete low-affinity IgM.  Early production of IgM can be detected in the serum within a few days of immunization.  APCs also ingest the peptide and travel to regional lymph nodes where they stimulate CD4 T lymphocytes to interact with activated B cells.  This interaction facilitates immunoglobulin class switching from IgM to other types (eg, IgG, IgA) and stimulates B-cell differentiation into memory B cells.  Plasma cells secrete high-affinity IgG, and levels peak a few weeks after immunization (after IgM peaks) before slowly waning (Choices B and E).

  • Secondary response:  subsequent vaccination or pathogen exposure results in a IgM response similar to initial vaccination due to stimulation of antigen-specific naïve B lymphocytes.  However, the previously formed memory B cells quickly differentiate into long-lasting plasma cells to produce a rapid and sustained IgG response that peaks around the same time as the IgM response but is greater in magnitude (Choices C and D).  IgG rapidly neutralizes invading organisms and is responsible for the protective effects of the vaccine.

Educational objective:
Initial vaccination generates an early IgM response by short-lived plasma cells followed by a delayed-onset, longer-lasting IgG response due to T-cell dependent class switching (IgM peaks before IgG).  Due to formation of memory B cells, secondary responses (eg, booster vaccination, pathogen exposure) are characterized by a rapid and sustained IgG response with a short-term, more muted IgM response.