Saturday, March 19, 2005

Lessons from the Acquired Immunity

Evolution has no foresight. Neither do we.

This is an age of insecurity. Hijacked planes, suicide bombs, weapons of mass destruction, phishing emails, computer viruses. We are under attack everywhere and everyday.

But this is also an age of protection. National security advisory code, airport shoe check, National Missile Defense system, liberation of Iraq, sophisticated message encryption, antivirus software, firewalls, deadbolts on the doors. We live behind the shields of better and better defense.

But are we protected? A recent commentary published in the journal Immunity should make us thinking again.

In his article, Stephen Hedrick re-exams the usefulness of the acquired immune system. The acquired immune system is vertebrates' second line of defense against pathogens, and it is activated when the first barrier against infection, the innate immune system, is breached. The acquired immunity employs a sophisticated mechanism -- somatic hypermutations combined with thymus or germinal center selections -- to generate pathogen-specific T-cells and B-cells to search and destroy the invaders. These T-cells and B-cells then remember their specific targets, and become a fast response force against any recurring infection. Thanks to the acquired immunity, we do not get many diseases twice, and we can be vaccinated against these diseases before they strike. In contrast, the innate immunity, which is universal to vertebrates and invertebrates alike, uses seemingly mundane mechanisms: cell membranes and coagulation to deny pathogen's access into host, defensins and lysozymes to destroy the parasites before their entry, and other brute force measures.

Until now, the majority of immunologists view the acquired immunity as an optimal defense system, a superior weapon that confers great health advantage onto vertebrates over invertebrates. Hedrick's commentary overturns this conventional view. He argues that the acquired immunity overall does not benefit vertebrates as a kind. Comparisons between insects and vertebrates have yielded several surprises. For example, the morbidity and mortality of insects due to infection are not higher than that of vertebrates. Compared to the pathogens for invertebrates, the pathogens that infect vertebrates have developed more adaptive strategies to evade the acquired immune system. Influenza is one best known example of this adaptability. Not only the acquired immunity can be easily rendered useless by the evasive pathogens, it can also be exploited by the viruses for their replication, as in the case of AIDS, or backfire on the host and cause autoimmune diseases such as arthritis and lupus.

Instead, the acquired immunity appeared to be an evolutionary misstep. The strain that first developed the acquired immunity had a temporary advantage over the rest of the animal kingdom, so it multiplied, eventually developing into the vertebrate subphylum. Unfortunately, it underestimated the infinite resourcefulness of the pathogens. The fateful genetic mutation that gave rise to the acquired immunity inadvertently escalated the war between the pathogens and the vertebrate hosts, one that had inflicted heavy costs and casualties on both sides for the past four hundred million years. Meanwhile, the acquired immunity becomes an absolute necessity for vertebrates, because any deficiency in it will make the individual defenseless against the highly evolved pathogens.

Hedrick’s insight should reach beyond immunologists.

So much as our sophisticated acquired immunity cannot make us impermeable to germs, any defense that we can mount against foreign or domestic attacks can be defeated by a clever enemy. It is an arms race that no one wins in the end. The National Missile Defense system will not protect us, because it will be easily overwhelmed by inexhaustible possibilities of countermeasures. Hundreds of billions of dollars will only buy the Americans a false sense of protection, and will prompt the Russians and the Chinese into a race to develop missile technologies capable of circumventing NMD.

Neither will the antivirus software make our PCs virus-free. After all, it can only recognize a known virus and is useless against any new strain. It seems that the real defense against computer viruses is plain caution: do not visit suspicious websites, do not download programs without a proper certificate, do not open emails from unknown senders. It is just like the innate immunity, mundane but effective.

Yet all is too late. The acquired immunity is here to stay. So is the National Missile Defense, so is the antivirus software, so is the spam email filter. They have all become the cause of their own necessity. We pay for their existence because they protect us from all known forms of attack. But by the force of the unknown future, we remain in the shadow of menace.

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