1. Autoimmunity disease is caused by failure of
tolerance processes to protect the host from the action
of self-reactive lymphocytes. These disease result from
the destruction of self proteins, cell, and organs by
auto-antibodies or self reactive T cells. For example,
auto-antibodies are the major offender in Hashimoto’s
thyroidtis, in which antibodies reactive with thyroid
specific antigens cause severe tissue destruction. On
the other hand, many autoimmune disease are
characterized by tissue destruction mediated directly by
T cells. A well known example is rheumatoid arthritis
(RT), in which self reactive T cells attack the tissue in
joints,
2. Causing an inflammatory response that result
in swelling and tissue destruction.
These diseases are often categorized as
either organ-specific or systemic, depending
on whether they affect a single organ or
multiple system in the body. In each case, we
discuss the antigenic target, the causative
process, and the resulting symptoms.
3.
4. In HT, an individual produces auto- antibodies
and sensitized TH1cells specific for thyroid
antigens. This disease much more common in
woman. Antibodies are formed to a number of
thyroid proteins, including thyroglobulin and
thyroid peroxidase, both of which are involved if
in the uptake of iodine. Binding of the auto-
antibodies to these proteins interferes with
iodine uptake, leading to dec. Thyroid function
and hypothyroidism(dec. Production of thyroid
hormones). The ensuing inflammatory response
cause a goiter, or enlargement of the thyroid
gland, a physiological response to
hypothyroidism.
5.
6. T1DM or insulin- dependent diabetes, affects almost 1000
children in the U.S.
It is seen mostly in youth under the age of 14 and less
common then Type 2, or non-insulin- dependent diabetes
mellitus. T1DM is caused by an autoimmune attack against
insulin- producing cells (beta cell) scattered throughout
the pancreas, which results in decreased production of
insulin and consequently increased levels of blood
glucose. The attack begins with cytotoxic T lymphocytes
(CTL) infiltration and activation of macrophages, frequently
referred to as insulities, followed by cytokine release and
the production of auto-antibodies, which leads to a cell
mediated DTH response. Auto-antibodies specific for beta
cells may contribute to cell destruction by facilitating
either antibody –mediated complement lysis or antibody –
dependent cell- mediated cytotoxicity (ADCC).
7. The abnormalities in glucose metabolism
associated with T1DM result in serious metabolic
problems that include ketoacidosis
(accumulation of ketone, a breakdown product
from fat) and increased urine production. The
last stages of the disease are often characterized
by atherosclerotic vascular lesion(which cause
gangrene of extremities due to impeded vascular
flow), renal failure, and blindness. If untreated,
death can result. The most common therapy for
T1DH is daily administration of insulin.
Unfortunately, diabetes can remain undetected
for many years, allowing irreparable los of
pancreatic tissue to occur before the treatment
begins.
8.
9. MS is the most common cause of neurologic disability
associated with disease in Western countries.MS occurs in
woman two to three times more frequently than men and,
like SLE (Systemic Lupus Erythematosus ) frequently
develops during childbearing years. Individuals with this
disease produce autoreactive T cell that participate in the
formation of inflammatory lesion along the myelin sheath
of nerve fibbers in the brain and spinal cord. Since myelin
functions to insulate the nerve fibers, a breakdown in the
myelin sheath leads to numerous neurologic dysfunction,
ranging from numbness in the limbs to paralysis or loss of
vision. The cause of Ms is not well understood. Infection
by certain viruses, such as Epstein-Barr virus (EBV), may
predispose a person to MS. Some viruses can cause
demyelinating diseases, but the data linking viruses to MS
are not definitive.
10. Environmental Factors Favouring the
Development of Autoimmune Disease
Some autoimmune syndromes are more
common in certain geographic locations or in a
particular climates. Infection may also influence
the induction of autoimmunity. For example,
tissue pathology following infection may result in
the release of sequestered self antigens that are
presented in a way that fosters immune
activation rather than tolerance induction.
Likewise, the molecular structures of certain
microbes may share chemical features with self
components, resulting the activation of immune
cells with cross- reactive potential.
11. In both organ specific and systemic autoimmunity,
CD4+ rather than CD8+ T cells have been linked to
disease pathogenesis. The antigen , the type of APC
to make first encounter, and the surface receptor used
during this engagement set the stage for the transition
from innate to adaptive immunity. In this transition,
cytokines milieu will help determine which subset of a
TH cell will predominate. The induction of
autoimmunity is likewise a complex process, where
even experimental model of the same human disease
can be induced by different means.
12. The induction of self tolerance in T cells results from exposure of
immature thymocytes to self antigens in the thymus, followed by
clonal deletion or inactivation of any self-reactive cells. Tissue
antigens that are not expressed in the thymus will not engage
with developing T cells and will thus not induce self tolerance.
Trauma to tissues following either an accident or an infection
can release these sequestered antigens into the circulation. For
instance, the release of heart muscle antigen following
myocardial infarction ( heart attack ) can leads to the formation
of auto-antibodies that target healthy heart muscle cells. Studies
involving injection of normally sequestered animal support this
proposed mechanism: injection of CNS myelin proteins or
pancreatic beta cells can inhibit the development of EAE or
diabetes, respectively. In these experiments, exposure of
immature T cells to self antigens normally not present in the
thymus presumably led to central and possibly also peripheral
tolerance to these antigen.
