Download Immune Senescence

Aging is associated with an increased frequency of infection and neoplastic disease. Alterations of the
immune system, especially T cell function, contribute to this phenomenon and are referred to as
immune senescence.
CHANGES IN T CELL FUNCTIONS
The involution of the thymus begins during the second decade of life and is complete by about age 50.
This decrease in thymocyte number leads to decreased production of T cells. The number of
thymocyte precursors produced in the bone marrow remains unchanged, but thymocyte maturation
declines with age. Involution of the thymus leads to a decreased ratio of naïve T cells to memory T
cells in the periphery. The decreased production in naïve T cells leads to a decline in T cell dependent
cell-mediated, which indirectly affects humoral immunity.
Despite the decreased production of T cells
from the thymus with advancing age, the
The involution of the thymus begins
overall number of circulating T cells is
during the second decade of life and
unchanged due to peripheral renewal and
is complete by age 50.
clonal expansion. Late in life, fewer
naïve T cells are present in the periphery, the rate of clonal expansion decreases, and more memory T
cells are circulating. Cytokine-dependent immune responses are altered by this shift from naïve to
memory T cells, and there is a change in the proportions of different cytokines. Naïve T cells produce
more IFN-and IL-2, whereas memory T cells in the elderly produce more IL-4 and IL-6. Likewise,
the ratio of CD4 to CD8 T cells significantly increases with aging.
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Histological appearance of thymi from a child (left) and an older adult (right)
CHANGES IN B CELL FUNCTIONS
The number of B cell precursors in the bone marrow decreases with age. However, the number of
circulating peripheral B cell lymphocytes is maintained through self-renewal and clonal expansion.
With aging, there is a shift in the ratio of CD5+:CD5- B cells with the normally less plentiful CD5+ B
cells becoming more frequent. CD5+ B lymphocytes are most frequently found in the peritoneal
cavity and often produce antibodies to autoantigens.
In an older adult, the immune response to
most vaccines is weakened, while the
frequency of autoantibody production
increases. Despite this increased frequency
of CD5+ B lymphocytes, the incidence of
autoimmune diseases, other than pernicious
anemia and autoimmune thyroiditis, is not
increased in older adults.
With aging, the frequency of CD5+
autoantibody-producing B cells
increases, while responses to
vaccine antigens become less
vigorous.
TEST YOUR UNDERSTANDING
Case 1
Mr. H is a 74-year-old Caucasian male who presents to the emergency department with a complaint of
intense burning pain in his right upper quadrant. The presumed initial diagnosis of gallbladder disease
is dispelled by normal radiologic tests. He is discharged home with pain medication. Ten days of
relentless pain later, he is noted to have a blistered rash on a red base. The rash is noted in the T5
dermatome. The rash subsides within two weeks, but he endures years of continued pain in this
distribution.
This is a common presentation of shingles or Varicella Zoster. It is caused by the reactivation of
varicella virus and the incidence increases significantly with age. Mr. H had chicken pox as a small
child. He asks the physician why, after nearly 70 years, the virus has suddenly reactivated.
How would you advise this patient?
Shingles, or Herpes Zoster is caused by the same virus that causes chickenpox. The Varicella Zoster
Virus (VZV) remains dormant in the dorsal spinal root ganglion neurons and the fifth cranial nerve
ganglion neurons until it is reactivated. Research has indicated that immune senescence leads to a
muted immune response to the VZV and an increased likelihood of reemergence of disease. When
older adults are skin tested with subcutaneous VZV antigens, their T cell-mediated delayed
hypersensitivity response is significantly less than in younger subjects. Shingles are much more likely
to occur in patients who are immunocompromised by disease or some cancers but also occurs in
otherwise healthy older adults.
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Typical Herpes Zoster
or Shingles rash on
the abdomen of an
elderly patient.
Case 2
Mrs. S is an 82 year-old healthy female who visits her doctor with questions regarding a pneumonia
vaccination. Her physician has been advising her to have the pneumovax vaccine for several years,
but she has been resistant. She has never
had pneumonia and she has read in the lay press that the pneumonia vaccination is less effective in
older adults. She is unsure why she should proceed with the vaccination in light of these facts.
How would you advise this patient?
Mrs. S is correct that pneumonia vaccination is less effective in older adults. Studies have shown that
older adults have significantly lessened antibody response to the vaccination. However, it is still
important for her to have the pneumovax vaccine as it is thought that even if she developed
pneumonia, her overall illness would be less severe.
The risk for developing pneumonia, regardless of vaccination status, is increased in older adults. Lung
elasticity decreases and respiratory muscle strength decreases with aging. This leads to an overall
diminished cough and impaired clearance of secretions. The age-related cumulative effect of diseases,
such as asthma or COPD, further impair pulmonary resistance to infection.