There are a number of thyroid
But by far the most common are the two that are 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 epithelial cells.
The autoantibodies that are bound to the thyroid
epithelial cells can activate the classical pathway of
complement, 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 agonists
to the receptor, they mimic the effect of TSH.
And therefore they are
Following binding to the TSH receptor, there
is stimulation of the thyroid epithelial
cells, just like thyroid stimulating hormone
would 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, there’s
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 these stimulatory autoantibodies.
So 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 these particular types of autoimmune disease,
there is a syndrome that is seen in the newborn
where the newborn baby has symptoms that are very
similar to the mother due to an autoimmune condition.
One of the best described examples
of this is neonatal thyrotoxicosis.
In the mother, she is producing IgG
antibodies against the TSH receptor.
So this lady has Grave’s disease.
But during pregnancy, IgG antibodies
are passed across the placenta.
Now most of those will 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 the placenta.
So the maternal IgG
crosses the placenta.
And this includes the anti-TSH
receptor stimulatory autoantibodies.
So this causes a condition that is very
similar to Grave’s disease in the neonate.
And this is referred to as
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
immunoflurescence tissue section of the 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,
because it 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 cell specific peptides shown to
the T-cell receptor on the cytotoxic T-lymphocyte.
And the result is the 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 apopototic cell death in the beta cells.