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The ‘bad’ antibodies in the immune system which are usually ‘silenced’ because they can harm the body can provide crucial protection against invading microbes. The ‘bad’ antibodies are known to react against the body’s tissues and can cause autoimmune disease. The new findings show for the first time that ‘bad’ antibodies go through a rapid ‘redemption’ process and are activated when the body is faced with a disease threat that other antibodies cannot handle.
The ‘bad’ antibodies no longer threaten the body, but become useful and fight disease that evade the immune system by disguising to look like normal body tissue. Professor Chris Goodnow, who co-led the new research with A/Prof Daniel Christ (both Immunology Division, Garvan), says the new findings will fundamentally change thinking about how the immune system protects human body. The research shows that every antibody is precious when it comes to fighting invading microbes, ‘bad’ antibodies are valuable resource for the development of vaccines for HIV and other diseases that go undercover in the body.
Campylobacter, HIV and others are problematic targets for the immune system because they appear identical to the body’s molecules; this makes it difficult for the immune system to attack them, because it systematically avoids using antibodies that can attack ‘self’. To understand how the immune system recognises these invaders, scientists from the Garvan Institute zeroed in on a mysterious army of immune cells in the bloodstream.
The silenced cell army contains millions of immune cells known as B cells that produce antibodies to fight diseases. Unlike other B cells, though, the cells of this army pose a danger to the body. This is because they can make ‘bad’ antibodies, which can attack ‘self’ and cause autoimmune disease. For this reason, they are kept in a long-term silenced state (known as anergy). Selected cells in the army can be reawakened to fight invaders when their ‘bad’ antibodies are made good.
Silenced cells do have a crucial purpose, they can produce antibodies when they encounter an invader that appears highly similar to ‘self’. Crucially, before the cells attack, the antibodies they make are first redeemed through tiny alterations to their DNA sequence. This ensures the antibody that each cell makes no longer attacks ‘self’, but rapidly becomes more potent weapon against the invading foreigner.
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