A 1-year-old boy is brought to the office for a health maintenance visit. He has had no significant health issues and is growing well. The patient is up to date with recommended vaccinations and has had no prior vaccine-related adverse events. He has no known allergies. Physical examination shows no abnormalities. The patient receives the first dose of the subcutaneous measles-mumps-rubella vaccine. The next day, his mother calls the office because the patient has a temperature of 38 C (100.4 F) and has been irritable since the vaccination. The immunization site is mildly red, swollen, and tender; there is no other skin rash. Which of the following cells and effector mechanisms is most likely involved in pathogenesis of this patient's current condition?

Question

A 1-year-old boy is brought to the office for a health maintenance visit.  He has had no significant health issues and is growing well.  The patient is up to date with recommended vaccinations and has had no prior vaccine-related adverse events.  He has no known allergies.  Physical examination shows no abnormalities.  The patient receives the first dose of the subcutaneous measles-mumps-rubella vaccine.  The next day, his mother calls the office because the patient has a temperature of 38 C (100.4 F) and has been irritable since the vaccination.  The immunization site is mildly red, swollen, and tender; there is no other skin rash.  Which of the following cells and effector mechanisms is most likely involved in pathogenesis of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3a6f_32a6_9249_41fad140ce50_MD0001_00 This boy developed fever, irritability, and local inflammatory symptoms (eg, redness, tenderness, swelling) within hours of vaccination, indicating reactogenicity, an inflammatory reaction that occurs shortly after vaccination. Vaccinations typically inject a foreign, unencountered antigen into subcutaneous tissue in order to promote the development of adaptive immunity against the antigen. However, foreign antigens can also trigger a rapid-onset innate immune response driven by the presence of pattern recognition receptors (eg, toll-like receptors) on local stromal and local/circulating immune cells (eg, macrophages, monocytes, mast cells). Pattern recognition receptors identify conserved motifs present on many pathogens (eg, lipopolysaccharide). Activation of these receptors leads to the release of pyrogenic cytokines (eg, TNF-alpha, IL-1, IL-6), which can cause local inflammation (eg, edema, warmth, swelling) due to increased vascular permeability/immune cell recruitment and systemic inflammation (eg, fever, irritability, fatigue, headache) due to increased circulating inflammatory cytokines. Many vaccines also contain adjuvants (eg, aluminum salts, virosomes, oil-in-water) to increase the immune response to the injected antigen. Adjuvants are strongly immunostimulatory and frequently increase the risk of reactogenicity. However, manifestations of reactogenicity tend to improve 24-36 hours after vaccination. (Choices A and C) Dendritic cells are antigen-presenting cells (APCs) that display foreign antigens on their surface on major histocompatibility complex class II molecules. CD4 T lymphocytes with antigen-specific receptors bind to the antigen on the APCs and are costimulated by the interaction between CD80/86 on the APCs and CD28 on the T-cell surface. Activated CD4 T-cells then increase display of CD40 ligand, which binds CD40 on the APC, leading to full APC maturation. These adaptive immune responses take several days to form and do not cause local reactions soon after vaccination. (Choice B) Cytotoxic T-cells recognize a foreign antigen on major histocompatibility complex class I and release perforins to induce cell lysis; they primarily attack cells infected by intracellular pathogens (eg, viruses). Cytotoxic T-cells do not significantly contribute to vaccination reactions within hours of vaccination. (Choice E) Some activated B-cells differentiate into short-lived plasma cells that secrete IgM. However, this typically takes several days to occur and would not cause local inflammatory symptoms. Educational objective: Vaccine reactogenicity is a local (eg, warmth, swelling, edema) and systemic (eg, fatigue, fever, headache) inflammatory reaction to the vaccine due to the innate immune response. It is primarily caused by pattern recognition receptors present on the surface of macrophages and mast cells, which identify the antigen and release inflammatory cytokines (eg, IL-1, IL-6).

A 1-Year-Old Boy Is Brought to the Office for a Health