A 75-year-old man is hospitalized due to respiratory distress. The patient developed fever, cough, and muscle aches 4 days prior to admission. He is otherwise healthy and has no chronic medical conditions. The patient has received all recommended vaccinations, including a yearly flu vaccine. Temperature is 39 C (102.2 F), blood pressure is 110/65 mm Hg, pulse is 115/min, and respirations are 29/min. Chest x-ray shows bilateral infiltrates. Reverse transcriptase PCR of a specimen from a nasopharyngeal swab reveals a strain of influenza A virus that was included in the seasonal trivalent flu vaccine. The patient lives with his 50-year-old son, who received the same vaccine but did not develop the infection. Which of the following factors most likely increased this patient's risk of vaccine failure compared with that of his son?
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Most of the protection provided by vaccines depends on antibodies generated by an immune response to pathogen-specific antigens. These antibodies can bind to the pathogen and directly neutralize it or facilitate elimination of the pathogen through phagocytosis, complement fixation, and/or antibody-dependent cytotoxicity. The risk of primary vaccine failure is increased in patients with altered immune function, including those with atopic disorders (eg, asthma, eczema), steroid use, or age-related immune decline (eg, immunosenescence).
The loss of telomere length during normal aging particularly affects rapidly dividing immune cells (eg, bone marrow stem cells, lymphocyte precursors), resulting in decreased production of naive B and T lymphocytes. Aging is also associated with chronic low-grade inflammation that causes much of the remaining naive lymphocyte pool to differentiate into memory lymphocytes against previously encountered antigens. These changes impair the adaptive immune response to novel antigens (eg, pathogens, vaccinations) and predispose these patients to vaccine failure and increased susceptibility to infection.
(Choices A and C) Antibody quality (ie, avidity for the target antigen) and levels of memory B and T lymphocytes are preserved with age, allowing most aging individuals to mount an effective immune response to previously encountered antigens.
(Choice D) Neutrophil-induced apoptosis is reduced in aging individuals, increasing susceptibility for nonhealing wounds/infections. However, a change in neutrophil function would not significantly impact the vaccine response.
(Choice E) Phagocytosis and antigen presentation by dendritic cells and macrophages decline with age, further impairing the immune response to novel antigens.
Educational objective:
Immunosenescense is the normal age-related decline that impairs most aspects of immune function, including the production of naive B and T cells. This results in a diminished antibody-based immune response to novel antigens (eg, infections, vaccinations). The immune response to previously experienced pathogens is typically intact due to normal or increased levels of memory B and T cells and preserved antibody quality.