Serum sickness

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.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.

All of 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 (ROS) 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 this person has 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 because 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 start 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 clinically when there are allergy-like symptoms that start a week or two after the first exposure to the foreign serum.The treatment for serum sickness is generally to use antihistamines and analgesics which help with symptoms; also, and very importantly, avoiding 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 within and damage to nearby tissues.

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 within and damage to nearby tissues Hi everyone Sara here Thank you for watching that video on serum sickness I hope you found it informative The brilliant script was written by Thomas Bush and the script was edited by Rishi Dezi and Yihan Chaw And then I did the illustration and the voiceover and the whole thing was edited by Sam Gillespie So big thanks to the team of osmosis for making it happen If you liked it you'd probably be aware that we've got loads more videos on our youtube channel which are really really helpful for simplifying and making medicine and healthcare subjects a lot easier to learn But one of the things we pride ourselves in at osmosis is making this information way more accessible for patients and people who are affected by these conditions So if you're one of them or if you're a student and you like what we do or you don't let us know we'd love to hear from you If you're a student what you should do is head over to osmosis dot org because there we've got loads more videos that aren't released on the youtube channel as well as questions flashcards basically everything you need to learn medical subjects