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.