Turning now to Goodpasture's Syndrome.
In Goodpasture's Syndrome, there are autoantibodies that bind to glomerular and to alveolar basement membrane.
These autoantibodies recognize the alpha-3 chain of type IV collagen.
This particular structure is found both in the kidney and in the lung.
Following binding of the autoantibodies there is activation of complement,
leading to glomerulonephritis in the kidney and the alveolar hemorrhage in the lung.
There are a number of thyroid autoimmune diseases but by far the most common are the two that is shown here.
Hashimoto's disease and Grave's disease.
In Hashimoto's disease, there are autoantibodies against the enzyme thyroid peroxidase
and against the molecule thyroglobulin which is a molecule upon which the thyroid hormones are generated.
Autoantibodies will bind to the thyroid epithelial cells and there will also be lymphocytic infiltration of the thyroid.
With subsequent destruction of the thyroid tissue by cytotoxic T-Lymphocytes releasing perforin and granzyme
which will destroy the thyroid epilthelial cells.
The autoantibodies that are bond to the thyroid epithelial cells can activate the classical pathway of complements
leading to the generation of the membrane attack complex which can also contribute to the damage.
The result of the destruction of the thyroid tissue is hypothyroidism,
an underactive thyroid with reduced production of thyroid hormone.
In contrast, in Grave's disease, there are autoantibodies that bind to the TSH receptor, the thyroid stimulating hormone receptor.
Crucially, these autoantibodies act as agonist to the receptor.
They mimic the effect of TSH and therefore they are stimulatory autoantibodies following binding to the TSH receptor,
there is stimulation of the thyroid epithelial cells just like thyroid stimulating hormone which stimulate the thyroid epithelial cells.
Here we have an autoantibody that is doing the same thing and this results in hyperthyroidism,
now, normally once we've made enough thyroid hormone as a feedback mechanism
that stops the production of more thyroid hormone,
reduces the level of TSH and everything will settle back to produce the needed level of thyroid hormone.
Here you have plasma cells that are constantly pumping out, they stimulate to your autoantibodies.
There is no negative feedback on the autoantibody so a constant stimulation of the thyroid leading to hyperthyroidism.
There is a very interesting condition that is associated with a small number of autoimmune diseases
and in this particular types of autoimmune disease, there is a syndrome that is seen in the newborn
where the new born baby has symptoms that are very similar to the mother due to an autoimmune condition.
One of the best describe examples of this is neonatal thyrotoxicosis.
In the mother, she is producing IgG antibodies, against the TSH receptor.
This lady has Grave's disease but during pregnancy, IgG antibodies pass across the placenta.
Now, most of those would be good IgG against common pathogens,
but if amongst those IgG antibodies that are against pathogens there are also autoantibodies of the IgG class, they can also go across placenta.
The maternal IgG crosses the placenta and this includes the anti-TSH receptor stimulate to your autoantibodies.
This causes a condition that is very similar to Grave’s disease in the neonate and this is referred to as neonatal thyrotoxicosis.
In Type I diabetes, the patient's serum contains IgG that has bound to cells in the pancreatic islet
that we can see here on this immunofluorescence tissue section of a pancreas.
We can see that the patient's serum is only staining one particular area of the pancreas.
The exocrine pancreas is not stained.
What is being stained here is the beta cells in the Islets of Langerhans,
becaus this is the beta cells in the pancreas that produce insulin
and the autoimmune attack is directed specifically towards the beta cells.
The autoantibodies that are present in Type I Diabetes include autoantibodies to insulin, to the enzyme glutamic acid decarboxylase,
to insulinoma antigen-2 (IA-2), and to the zinc transporter 8.
These autoantibodies will bind to the surface of the beta cells,
there is also lymphocytic infiltration of the pancreas, with cytotoxic T-Lymphocytes
recognizing pancreas specific or beta cells specific, peptide shown to the T-cell receptor on the cytotoxic T-Lymphocyte
and the result is destruction of the beta cells in the Islets of Langerhans leading to hyperglycemia.
Again, the autoantibodies activating complement causing the generation of the membrane, attack complex and the cytotoxic T-cells
releasing perforin and granzymes causing apoptotic cell death in the beta cells.