Serum Sickness – causes, symptoms, diagnosis, treatment, pathology

Let’s imagine for a minute that you found
yourself in the somewhat unfavorable position of having being bitten by a venomous snake. Now, to treat that, you might get injected
with anti-venom, which is the serum, or just the liquid part of blood and it’s had the
coagulation proteins removed, and it comes from another animal, like a mouse, and that
mouse has already encountered that particular venom and so it’s developed antibodies against
it. These antibodies can bind to the venom molecules
and render them harmless. Now normally that’s the end of that, but in
serum sickness, your immune system actually mounts an attack against the foreign serum. It’s just like attacking a friendly police
officer that’s trying to help you out. Serum sickness is a type III hypersensitivity
reaction, which means that it’s mediated by immune complexes, which are combinations
of antibodies and soluble antigens, in this case the antigens are the foreign antibodies
in the serum. Now normally, antibodies, which are sometimes
called immunoglobulins, are produced by plasma cells, which are fully mature and differentiated
B cells. B cells have multiple IgM antibodies on their
surface and they act like receptors. When an antigen binds to two of these receptors
it’s called cross-linking. This triggers the B cell to take in the antigen,
break it all apart, and present a piece on the surface on a protein called MHC class
II, which stands for major histocompatibility complex class II. Nearby T helper cells can then bind to the
MHC class II protein via their T cell receptor, this happens along with costimulatory molecule
CD4. The B cell’s CD40 also binds to the T cell’s
CD40 ligand, and that causes the T cell to release cytokines, which then results in B
cell activation and class switching, or isotype switching. This means that it changes from producing
IgM antibodies to producing IgG antibodies instead. After class switching, B cells become plasma
cells and they focus on producing large amounts of this IgG antibody. The IgG antibodies bind to the antigen on
pathogens like a bacterium the IgG antibodies would bind to the antigen on the bacterium
and mark it for destruction by macrophages and neutrophils.. In serum sickness, however, plasma cells start
producing IgG antibodies in response to the antibodies in foreign serum that gets mistaken
for a harmful antigen. This process all starts with the initial exposure
exposure to the foreign antibodies that triggers the B cells to become plasma cells and produce
IgG antibodies against the foreign antibodies; and this all usually takes 4 to 10 days. If there are still foreign antibodies around,
the IgG will bind to them and form immune complexes. Since multiple IgGs can bind to the same antigen,
we end up with large immune complexes that then get deposited in the basement membrane
of blood vessels. This can happen in blood vessels throughout
the body, and that explains the various symptoms that can develop from serum sickness. Once these immune complexes are deposited
in the basement membrane, they activate something called the complement system which is made
up of tiny proteins in the blood that attract nearby neutrophils. So, neutrophils come to the area and degranulate,
which means they dump a bunch of lysosomal enzymes and reactive oxygen species on the
surface of the blood vessels, and this causes tissue necrosis and inflammation. They also release cytokines which are tiny
signal proteins that attract additional immune cells, that’s why there’s local inflammation
as well as systemic inflammation. Now, let’s say that this person were to
have a second exposure to the serum. In that situation, the whole reaction would
be much, much faster, happening within hours, and it would also be much more potent since
there are already tons and tons of plasma cells from the first exposure, and these are
all prepped and ready to produce IgG antibodies against the antigen. The symptoms of serum sickness include fever,
rashes, and itching and these usually starts within one or two weeks after the initial
exposure to the serum or 12 to 36 hours after a second exposure. There might also be lymphadenopathy, or swelling
of lymph nodes, proteinuria which is an increase in the concentration of protein in the urine,
and arthralgia, which is joint pain. The diagnosis is usually made when there are
allergy-like symptoms that start a week or two after a first-time exposure to foreign
serum. The treatment for serum sickness is generally
to use antihistamines and analgesics which help with symptoms and to avoid the serum
that triggered the reaction in the future. OK, so to recap the main points…serum sickness
is a type III hypersensitivity reaction where foreign blood serum causes an allergy-like
response. This happens when small, soluble antigens,
so the foreign serum, elicit the production of antibodies, and those antigens and antibodies
bind together to form immune complexes. These immune complexes then build up on the
basement membrane of blood vessels in various parts of the body, and then the complement
system is activated and this causes inflammation in and damage to nearby tissues.