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Antibody-mediated autoimmune diseases
الخميس، 5 مارس 2015
الأربعاء، 4 سبتمبر 2013
المحاضرة الثانية
In some autoimmune diseases autoantibody is the only or main
autoimmune feature of the disease and the pathology can be
explained by the actions of the autoantibody. Therefore it is easy
to classify these as antibody-mediated autoimmune diseases.
Different classes of autoantibody, with different functions, can be produced in
autoimmune diseases and cause pathology in a number of ways:
1. Complement-mediated
lysis:
Autoantibody binding to red blood cells can
result in complement fixation and lysis of the red cells, leading to autoimmune
haemolytic anaemia
2. Opsonisation:
In autoimmune thrombocytopenia autoantibody
binds to platelets and promotes their opsonisation by phagocytes in the liver
and spleen (Figure.4). This leads to platelet deficiency (thrombocytopenia) and
poor clotting.
3. Inhibition
of receptor function:
The disease myasthenia gravis involves the
production of antibodies against the acetyl choline receptor, which is present
on muscle fibers of the neuromuscular junction. The autoantibodies bind to the
acetyl choline receptors and prevent the binding of acetyl choline released at
the nerve endings. This blocks transmission of signals across the neuromuscular
junction, leading to muscle weakness.
4. Stimulation
of receptors:
For reasons that are not understood, in
some cases antibodies against receptors can stimulate the receptor rather than
block it. This happens in Grave’s disease where autoantibodies are produced
against the thyroid-stimulating hormone (TSH) receptor present on thyroid
epithelial cells (Figure.5). Stimulation of these cells results in thyroid
overactivity with the symptoms of hyper-thyroidism – nervousness, tiredness, weight
loss despite a good appetite and proptosis (bulging of the eyes).
5. Blockage
of biological function:
Some autoantibodies block the function of
molecules other than receptors. Pernicious anemia results from autoantibodies
against intrinsic factor. Intrinsic factor is produced in the stomach and binds
to vitamin B12, enabling B12 to be absorbed from the intestine (Figure.6). The
autoantibodies against intrinsic factor prevent the binding of B12 and hence
its absorption, resulting in vitamin B12 deficiency. The vitamin deficiency
leads to a lack of platelets and leukocytes and neurological changes.
6. Deposition
of immune complexes:
In SLE, immune complexes fail to be cleared
from the blood and are deposited in various sites such as the kidney, skin and
joints. The immune complexes then fix complement, which leads to an inflammatory
response and damage to the affected tissues. In SLE this results in kidney and
joint damage and characteristic skin rashes.
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