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Type III hypersensitivity
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Type III hypersensitivity

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In type III hypersensitivity reactions, B-cells produce antibodies rather than immunoglobulin M. 

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A 49-year-old woman comes to the office for management of her autoimmune disease. Her last urinalysis showed hematuria and casts. Laboratory testing showed elevated anti-DNA titers and low C3 and C4. A kidney biopsy is performed and shows subendothelial deposits on electron microscopy and wire loop appearance on light microscopy. Increase in which of the following is most likely involved in this patient's nephritis?

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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.