The gradual deterioration in immune function that occurs with aging
is manifest both as reduced in vitro immune responsiveness and impaired
immune response to
acute infection.
vaccination (e.g. intramuscular (IM) influenza vaccines are only 30-40%
effective in preventing clinical illness among the frail elderly individuals
vs. 70-90% in young adults, and their effectiveness in eliciting mucosal
response may be even lower. Subjects who respond to influenza vaccination
show a significant increase in serum HLA class I levels 2 weeks after immunization
: 2 forms of sHLA class I molecules of relative mass of Mr 42,000
and 40,000 are immunoprecipitated from the serum of nonresponders whereas
only the M(r) 40,000 form is detected in the sera of young controls and
of elderly respondersref.
A novel inactivated intranasal (IN) trivalent whole influenza virus vaccine
is significantly more effective than the IM vaccine in inducing mucosal
IgA response in nursing-home elderlyref)
Innate immunity : the functions
of NK cells, macrophages, and neutrophils, crucial cellular components
of innate immunity, are decreased with aging. In the aged mouse
AMs are decreased in number and are not efficient at presenting Ag to T
cells, and more macrophages are needed to effectively activate a T cell
neutrophils have impaired chemotaxis, degranulation, and phagocytosis :
the detrimental effect of stress on the immune response increases with
age, though the mechanisms responsible are not fully understood. The physiological
response to stress is regulated in part by the adrenocortical system. Adrenal
hormones dehydroepiandrosterone sulphate (DHEAS) and cortisol have opposing
effects on the innate immune system, DHEAS enhances while cortisol suppresses
immunity
and the molar ratio of cortisol to DHEAS increases with age. Ederly hip
fracture patients produced a robust neutrophilia after injury, but circulating
neutrophils showed an impaired antibacterial response. Adrenocortical hormones
mediate the heightened immunosuppression seen in the elderly after injury.
Neutrophil function and adrenocortical hormone levels were examined in
elderly (> 65 years) hip fracture patients and age-matched healthy controls.
Thirteen out of 35 elderly patients acquired infections following hip fracture.
Neutrophil superoxide production was lower in elderly hip fracture patients
compared with controls (P < 0.005) and lower in patients who acquired
infection following injury compared with those who did not (P < 0.05).
Serum cortisol:DHEAS ratio was higher in elderly hip fracture patients
(0.56 +/- 0.38) compared with either age-matched controls (0.36 +/- 0.21;
P < 0.05) or young fracture patients (0.087 +/- 0.033; P < 0.0001).
Moreover, cortisol: DHEAS was increased in elderly patients who succumbed
to infection compared with those who did not (0.803 +/- 0.42 vs. 0.467
+/- 0.28; P < 0.02). In vitro cortisol significantly decreased
neutrophil superoxide generation (P < 0.05) and this was prevented by
coincubation with DHEAS. Increased cortisol:DHEAS ratios may contribute
to reduced immunity following physical stress in the elderlyref.
Because macrophages, NK cells, and neutrophils provide the first line of
defense against bacterial and viral infections, the decline in function
could possibly explain the increased incidence of bacterial and viral pneumonias
and gastrointestinal and skin infections in the aged as well as diminished
protective immune responses to pneumococcal and influenza vaccines. Both
splenic and activated peritoneal macrophages from aged mice express significantly
lower levels of al TLRs and secrete lower IL-6
and TNF-a
when stimulated.
Adaptive immunity : people older
than 60 who showed shorter-than-average telomeres
have 86% higher death rate over the next 15 years than others, especially
from heart disease and pneumonia. They run a 3-fold higher risk of dying
from heart disease and an 8-fold higher risk of death from infectious disease,
almost entirely pneumonia. Their rates of death from stroke and cancer
are higher, but by too little to be considered meaningful. That might mean
that short telomeres leave immune system cells with less capacity to multiply
for fighting off infections.
cell-mediated immunity
the expression of CAMs on APCs and T cells declines, possibly contributing
to immune dysfunction
as the thymus atrophies with age, there are fewer naive
T cells available to respond to new pathogens and neoantigens, with
a concomitant accumulation of (oligo)clonally expanded memory CD8+28-57+
T cells (T cell clonal expansions (TCE)) (> 80% of the total CD8+
population), whose presence has been directly correlated with poor immune
function. Anyway the age-associated alterations in naive CD8+
cell function are not found after primary stimulation, but may become apparent
upon restimulation. This shift from naive to memory cells also causes
a shift in the cytokine environment.
with increasing age, CD45RA+naive cells are replaced
by CD45RA- memory CD4+ T cells.
in the CD8+ T-cell subset, there is an increased proportion
of cells co-expressing CD57
in monocytes also, some alterations of the immunophenotype, for example
the expression of the adhesion molecule CD54, are observed
a relative deficit of transendothelial migration with aging was found in
T cells, whereas this function was not impaired in monocytes
the immunophenotype and the function of dendritic cells do no t appear
to be affected by aging. Due to their capacity to present antigens to T
cells and to induce T-cell proliferation, dendritic cells may provide a
useful tool for immunotherapyref
antibody-mediated immunity
: aging is accompanied by greatly reduced B cell production in the bone
marrow, yet peripheral B cell numbers do not decline. This may reflect
filling
of the peripheral pool with B cells that are long-lived as a consequence
of specifity for, and chronic stimulation by, environmental Ags (a novel
form of receptor revision in which B cells are selected rather than deleted
based on Ag reactivity). It has been suggested that the dimished ability
to generate high-affinity protective Abs against infectious agents may
be due to inefficient somatic hypermutation in the V gene segments of the
Abs, inefficient help by aged Th cells, and the altered cytokine
environment. It is postulated that the Ab repertoire maturation in aged
mice is delayed and may be notably improved by repeated immunizations.
There is an increase in the asymmetric
IgG
: symmetric IgG ratio with aging.
Immune senescence is a factor in the increased susceptibility of the elderly
to infectious diseases, such as pneumonias, urinary tract infections, and
tuberculosis : decrease of immune surveillance could be a factor in the
increasing incidence of cancer with increasin age. The age-associated increase
in autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus,
and glomerulonephritis, certainly results from deterioration of the immune
system. Specifically, there is a loss in the ability to distinguish between
self and non-self.
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