basics of the immune system
Acquired hemophilia A is caused by a person's immune system "mistakenly" making an inhibitor to factor VIII. It is one of the many medical conditions that have puzzled doctors, because it is caused by an immune response activated not in the presence of an infectious agent (such as from bacteria or a virus). To understand what is happening in the body when an immune response is activated in the absence of infection, it is useful to understand the basics of the immune system (and the study of the immune system, or immunology) in the context of acquired hemophilia A. If you have any questions, please ask your doctor, as I have simplified the very complex language and workings of immunology for this page from a textbook I used in college (CA Janeway, et al. Immunobiology, 4th ed., Elsevier Publishing Ltd/Garland Publishing, 1999).

inhibitors
Simply, in scientific terms, an inhibitor is something that prevents some other thing from doing its job. If you have ever taken a chemistry class, you probably remember that a non-naturally occurring competitive inhibitor is something that can be put into a reaction and prevent the natural substrate, one part of the reaction, from binding to the second part of the reaction. If the natural substrate never gets the chance to bind to the second part, this has dire consequences, because the reaction between the natural substrate and the second part will never occur.

It was never fully explained to me whether the agent acting to destroy or make factor VIII inactive in a person with acquired hemophilia A was an inhibitor or an antibody. However, the most important thing you need to know about acquired hemophilia A is that factor VIII levels are so low or undetectable by blood tests and therefore cannot be counted on to perform normally in the formation of a blood clot.

antibodies - why they are made, where they come from, and how they work

• Antibodies are made in response to seeing an invader (an infectious agent) for the first time. This explains how vaccines are effective in preventing disease. The particles inside a flu shot, for example, are not complete, infectious flu viruses, but appear to the immune system to look enough like a complete flu virus. Your body's immune system will mount an immune response, with the final result being that antibodies to that invader are made. If the immune cells in your body ever encounter another invader that looks similar, these antibodies generated will be called in to help get rid of the invader.
• Antibodies come from B cells. B cells are the precursors of antibodies. In a very complicated and regulated "dance" of lots of cells interacting, activating, and signaling each other, as well as undergoing genetic recombination, antibodies are "born." In people with autoimmune disorders, antibodies are made incorrectly, because the immune system gets confused and makes antibodies against parts of the body or blood that are normal and should be there. I believe this is how the factor VIII inhibitor is generated in acquired hemophilia A, but I don't know if there is direct evidence of this. There may not be, considering that it is still unclear why acquired hemophilia A occurs in some people in the first place.
• Antibodies work in three major ways - neutralization, opsonization, and complement activation. In neutralization, antibodies may surround an invader and prevent it from binding to a cell surface, where it can fuse with the cell and cause damage. In opsonization, the antibodies help the body "eat" the entire invader (a process called phagocytosis). Complement is the collective name for a group of proteins that works with antibodies to get rid of invaders. Antibodies themselves can help activate the complement cascade and speed up the elimination process.

  On the National Center for Biotechnology Information (NCBI) page by the National Library of Medicine (NLM), this diagram (from CA Janeway, et al. Immunobiology, 5th ed., Garland Publishing, 2001) shows the three ways antibodies assist in the immune response against a foreign invader. The yellow Y-shaped molecules represent antibodies.

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M. Chang
19 November 2006

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