As we get older, things begin to go wrong, and
the immune system is no exception to this.
particularly affects T-cells.
The thymus shrinks by about 3%
each year following puberty.
And therefore, there is a reduced
production of naïve T-cells.
In infancy, the thymus produces T-cells
with a mixture of different specificities.
The T-cell numbers in the peripheral pool are
maintained by replication of circulating cells.
In early adult life, the
thymus produces fewer T-cells.
Proliferation in the periphery
maintains the size of the T-cell pool.
Replicative senescence related to the shortening of
telomeres limits the number of times a cell can divide.
Cytomegalovirus-specific T-cells become dominant
at the expense of other specificities during aging.
And the response to vaccines
and to infection declines.
So in the elderly, nearly no new
T-cells are produced by the thymus.
And this replicative senescence makes it harder for
proliferation in the periphery to maintain T-cell numbers.
In addition, the T-cell pool
has become very oligoclonal.
That means there are very few
different clones of T-cells.
Their specificity becomes
more limited as we age.
In fact as we age, neutrophils have a lower ability to produce
reactive oxygen species, they have a lower ability to be
chemotactically attracted to the site of the infection, and
they have a reduced ability to phagocytose microorganisms.
Dendritic cells have a reduced ability
to co-stimulate for T-cell activation.
Macrophages again like neutrophils, have a reduced ability to
produce reactive oxygen species,
also to produce reactive nitrogen
intermediates, the amount of IL-6
they can produce goes down, and the
amount of prostaglandin E2, a
pro-inflammatory substance goes up.
Natural killer cells have reduced
cytokine production and a decreased
ability to kill infected cells, in
other words reduced cytotoxicity.
Antibody levels overall do not decline, but there
is a reduced affinity of the antibodies produced,
and also there are greater numbers of autoantibodies
against self antigens that are produced.
Infection can be an important cause
of secondary immunodeficiency.
So to just give you a few examples; Example
of a parasite- malaria, a protozoan parasite.
In malaria, hemozoin which is produced from
host hemoglobin upon infection with the
Plasmodium species that causes malaria, this
substance inhibits dendritic cell function.
An example of a virus
- the measles virus.
Infection of dendritic cells leads
to reduced T-cell responsiveness.
Example amongst the
bacteria - Staphylococcus.
The toxic shock syndrome that you
see in Staphylococcal infections
is caused by a superantigen that leads to T-cell exhaustion.
A superantigen is a molecule that stimulates
lots and lots and lots of different
T-cell clones, not just the ones specific
for the antigen, but many others as well.
And then finally of course, the Human Immunodeficiency Virus
that leads to the Acquired Immune Deficiency Syndrome (AIDS).