The immune system is a complex of organs--highly specialized cells
and even a circulatory system separate from blood vessels--all of which
work together to clear infection from the body.
The organs of the immune system, positioned throughout the body, are
called lymphoid organs. The word "lymph" in Greek means a pure, clear
stream--an appropriate description considering its appearance and
purpose.
Cells that will grow into the many types of more specialized cells
that circulate throughout the immune system are produced in the bone
marrow. This nutrient-rich, spongy tissue is found in the center shafts
of certain long, flat bones of the body, such as the bones of the
pelvis. The cells most relevant for understanding vaccines are the
lymphocytes, numbering close to one trillion.
Scientists have gained important new insights into the underlying
causes of age-related changes in the immune system which lead to
decreased immune function and increased vulnerability to infectious
diseases in older people.
T-cells sometimes called "T-helper cells" play a central role in the
immune response, signalling other cells in the immune system to perform
their special functions. They play an important immune regulatory
function and are critical components in defenses against cancer as well
as a variety of infectious agents (bacterial, viral, fungal).
Age-related defects in T-cell function also can contribute to the
diminished response to immunization in older adults.
One process which was found to become abnormal in T-cells from aged
mice is called apoptosis. Sometimes referred to as programmed cell
death, apoptosis is thought to provide a critical step in the
regulation of T-cell response by removing cells with defects and by
maintaining appropriate levels of T-cells. Apoptosis is necessary for
the removal of inactive or senescent T-cells that may accumulate with
age, leading to decreases in immune function.
HIV disease is characterized by a gradual deterioration of immune
function. Most notably, crucial immune cells called CD4+ T cells are
disabled and killed during the typical course of infection.
Scientists have also discovered that telomerase is present at high
levels during both the development and activation stages of immune
cells and that this may affect the way the immune system is turned on
and regulated. Telomerase, previously thought to be present only in
"immortal" cells like sperm, egg, and tumor cells, is also present in
normal human immune cells.
Telomerase regulates DNA length by replenishing the ends of DNA
strands, called telomeres. These end segments are thought to be
responsible, in part, for maintaining the structural integrity of DNA.
In most types of cells, telomeres shorten as the cell ages, but in
tumor cells, and also in normal immune cells, telomerase might help
slow this shortening.
Research has led to improved therapy for individuals with primary immunodeficiency diseases.
Bone Marrow Transplantation
Transplantation of bone marrow cells from a family member with
identical human leukocyte antigens (HLA) has led to normal immune
function in patients with combined immunodeficiencies. HLA proteins
mark the donor tissue as self, which minimizes the potential for
rejection by the recipient's immune system. Investigators are working
to improve success using bone marrow from an unrelated HLA-matched
donor for the two-thirds of patients who lack an HLA-identical family
member and to use stem cell transplantation (stem cells can generate
all the cells of the immune system).
Replacement of Antibodies
Research has demonstrated the safety and efficacy of replacement
therapy with intravenous immunoglobulin (i.e., antibodies) in patients
with defects in antibody production. This treatment is life saving,
prevents many types of infection, and should be given to all primary
immunodeficiency disease patients with defects in antibody production.
Antimicrobials
The use of antibiotics to treat and prevent infections is a key element in the treatment of primary immunodeficiency disease patients. National Institute of Allergy and Infectious Diseases
- supported investigators helped identify new antimicrobial agents and
new treatment regimens. For example, NIAID researchers showed that
chronic granulomatous disease patients receiving daily doses of the
antibiotic cotrimoxazole had 65 percent fewer infections.
Immunomodulation
Immune system molecules can be injected into patients to improve
immune function. NIAID researchers showed that the immune system
molecule interferon gamma improves the function of the white blood
cells called neutrophils in patients with chronic granulomatous
disease, reducing infections by 70 percent.
