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of pharmacology and clinical reasoning topics. Try it free today. Having a hypersensitivity means that someone’s
immune system has reacted to something in a way that ends up damaging them, as opposed
to protecting them. There are four different hypersensitivities
and the third type or type III hypersensitivity reaction happens when antigen-antibody complexes
deposit in blood vessel walls, causing inflammation and tissue damage. Alright so first off, type III hypersensitivity
reactions are mediated by immune complexes. Immune complexes, aka antigen-antibody complexes
are made of two parts—the antigen and the antibody. Antibodies, sometimes called immunoglobulins,
are produced by plasma cells, which are basically fully matured and differentiated B cells. Initially these cells make IgM - which can
be secreted or bound to the plasma cell surface where it acts as a B cell receptor. When a B cell undergoes cross-linking of two
surface bound IgMs, it then takes up the antigen and presents a piece of it to T helper cells
via t cell receptor to the MHC- class II molecule presenting the piece of antigen, along with
costimulatory molecule CD4. The B cell’s CD40 also binds to the T cell’s
CD40 ligand, and then the t cell releases cytokines, which results in b cell activation
and class switching, or isotype switching, where it changes the type of antibodies it
makes. In type III hypersensitivity reactions, typically
B cells will switch from making IgM to making IgG antibodies. Now remember that all antibodies are specific,
right? Meaning that they recognize specific molecules
called antigens, the second part of immune complexes. Antigens can come in all sorts of flavors,
some float around in the blood by themselves, and are soluble, but some are bound to cell
surfaces. Immune complexes are formed when antibodies
bind to soluble antigens. Antibodies can also target antigens on cell
surfaces, but these are not considered immune complexes. This is the first major distinction between
type II hypersensitivity reactions, which involve antibodies binding to antigens on
cell surfaces, and type III hypersensitivity reactions, which involve immune complexes
with soluble antigens. A good example of a type III Hypersensitivity
is the autoimmune disease systemic lupus erythematosus, also just called lupus. In lupus, the IgG antibodies are typically
specific for DNA and nucleoproteins, both of which are part of your own cells, making
them self-reactive. Normally, your body should only react to things
that are foreign or not-self. And this is maintained by a process known
as tolerance where only non-self-reactive B and T cells are allowed to mature, whereas
self-reactive B and T cells aren’t. This process, though, isn’t perfect and
sometimes, some self-reactive cells escape, and these can mount an immune response against
autoantigens or self-antigens. With lupus, a DNA autoantigen may get released
from a damaged cell where a circulating self-B cell might find it and bind to it. If a T helper cell that is also specific for
the same DNA autoantigen is close by, it will help activate the B cell and enable it to
differentiate into an IgG secreting machine specific to that DNA autoantigen. Now what? Well, first off, there may be lots of this
DNA autoantigen around since DNA is in most human cells, right? Which allows a lot of IgG-DNA autoantigen
complexes to form. Now, if this were an infection, there would
be lots of antibodies surrounding a large single microbe which marks it for destruction
by macrophages and other phagocytes. But in this case, the antibodies are trying
to bind a small, soluble antigen and there may be a lot of antigen relative to the number
of antibodies. Small antigen-antibody complexes are less
immunogenic meaning they’re less attractive to the macrophages, and they don’t get removed
from the bloodstream as quickly. As a result, the immune complexes float around
in the blood longer, and typically make their way into the basement membrane layer of various
blood vessels. At this point, you’ve got immune complexes
ionically attached to or deposited in a larger structure, the basement membrane. Once deposited, the immune complexes activate
the complement system, a family of 9 small proteins called C1 through C9 that work in
an enzymatic cascade to clear infections in various ways. In this case, C1 binds the antibody-antigen
complex setting off a chain reaction and activates C2 through C9. When a complement protein becomes “activated”,
it’s often cleaved or chopped by an enzyme, which results in little fragments. Fragments C3a, C4a, and C5a are anaphylatoxins,
and increase vascular permeability, meaning fluid leaks out more easily, which causes
edema or fluid buildup. And this is the second major distinction between
type II hypersensitivity where complement proteins are activated in relatively small
amounts, and type III hypersensitivity reactions where complement proteins are rapidly consumed
in large amounts, specifically C3 and C4, which means that complement levels in the
blood can be used to track disease progression over time. The second thing C3a, C4a, and C5a do is act
as chemokines, meaning they recruit other cells like neutrophils to the site. Now, once neutrophils join the party, they
try and phagocytize the immune complex, but usually can’t. During this process, they degranulate, meaning
they dump a bunch of lysosomal enzymes and reactive oxygen species which cause inflammation
and tissue necrosis, which ultimately causes vasculitis or inflammation of the blood vessels. With inflammation comes further cellular destruction,
and more autoantigen release, repeating the cycle again. This most commonly takes place in areas like
the kidney where the blood is being filtered - causing glomerulonephritis, as well as the
joints, since blood plasma is being filtered to produce synovial fluid— and this causes
inflammation of the joints, or arthritis. This brings up a third major distinction between
type II hypersensitivity, where clinical symptoms correspond to the tissue where antibodies
attach to and destroy cells, and type III hypersensitivity, where clinical symptoms
correspond to the tissue where immune complexes are deposited, not where the immune complexes
are made. Now another example of a type III hypersensitivity
is serum sickness, which typically happens when a patient receives foreign serum and
elicits an antibody response against those foreign antigens. A classic example would be to get bitten by
a snake, and then get serum with anti-venom antibodies. In response the body would make some antibodies
against the anti-venom antibodies. Now if the person gets bitten by a snake again
some time later, and gets serum with anti-venom antibodies again, those antibodies that were
made the first time around will bind up and make immune complexes with the anti-venom
antibodies which are treated like an antigen. These immune complexes then cause vasculitis
and tissue necrosis, and would teach a person not to play with snakes.