Looking at autoimmune hemolytic anemia, one
can identify two types of autoantibody.
The cold antibodies are anti red blood cell autoantibodies
that only bind at significantly below normal body temperature.
And therefore the extremities
are particularly affected.
These antibodies are
usually of the IgM class.
In contrast, the warm type antibodies
found in autoimmune hemolytic anemia are
anti red blood cell autoantibodies
that bind at normal body temperatures.
And these are usually
of the IgG class.
Following binding of IgM or IgG autoantibodies to
the surface of the red blood cells, the classical
pathway of complement can become activated leading
to the generation of the membrane attack complex.
This will cause lysis
of the red blood cells.
In addition, phagocytic cells with Fc receptors on
their cell surface can take up erythrocytes that
have been coated with antibody, and this again will
lead to the destruction of those red blood cells.
One can test for the presence of these
autoantibodies using a test called the Coombs test.
And there are two different
versions of this test.
In the direct test, one takes a blood
sample from the patient and looks for
the presence of autoantibodies that are
already coating the red blood cells.
And one detects the presence of these
autoantibodies that have already coated
the red blood cells, using a second
antibody - an anti-human immunoglobulin.
This will cross link together the
antibodies on the surface of the red
blood cells causing agglutination
which can be visualized by the eye.
In the indirect test, one looks for
the presence of the autoantibody
itself, free autoantibody that
is not bound to the erythrocytes.
One can take this antibody from the serum
of patients, mix it with red blood cells.
And if the autoantibody has
specificity for red blood cells, this
anti red blood cell autoantibody
will bind to the red blood cells.
And this autoantibody can then again be detected by
using a second antibody, an anti-human immunoglobulin.
So this is the indirect Coombs test.
And again, upon adding the anti-human
immunoglobulin, there will be agglutination which
can be visualized by simply looking at the
slide on which this test is being carried out.
In pernicious anemia, there is a autoimmune attack that
prevents the absorption of vitamin B12 from the gut.
So in the normal individual, ingested vitamin B12
is picked up by intrinsic factor in the stomach.
And this complex of vitamin B12 bound
to intrinsic factor is then absorbed
from the gut and can be used in the
development of red blood cells.
However in pernicious anemia, there
are autoantibodies being produced.
One of those autoantibodies is against
the parietal cell H+ K+ ATPase.
This leads to a reduced
production of intrinsic factor.
And there are also autoantibodies
against intrinsic factor itself.
This means that vitamin B12 is not
absorbed from the gut resulting in anemia.
In autoimmune thrombocytopenic
purpura, platelets are affected.
There are autoantibodies to the platelet
glycoproteins GPIIb-IIIa and GPIb-IX.
These are removed and destroyed by splenic
macrophages and liver Kupffer cells.
So following binding of these
autoantibodies to the platelets, the complex
of the autoantibody together with
the platelet is recognized by Fc
gamma receptors on the surface of these
phagocytic cells and the platelets
are destroyed, resulting in autoimmune thrombocytopenic purpura.