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Serum sickness



Immune system


General infections
Hypersensitivity reactions
Immune system organ disorders
Immune system pathology review

Serum sickness


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Serum sickness

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Let's imagine for a minute that you found yourself in the somewhat unfavorable position of having been 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. If this situation was an immune response to a pathogen 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 to the foreign antibodies which 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.


Serum sickness is a type III hypersensitivity reaction in which a foreign blood serum causes an allergy-like response. This happens when small, soluble foreign serum, elicits 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. Symptoms include fever, urticaria, arthralgia, proteinuria, and lymphadenopathy. 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.

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  7. "Serum Sickness" Pediatric Clinical Advisor (2007)
  8. "Serum Sickness" Pediatric Emergency Medicine (2008)