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How Lyme Disease Affects the Immune System
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September 8, 2010
Getting Lyme
Lyme disease is like no other bacterial infection. With most bacterial infections, you expect to take an antibiotic and be over the infection within a week to 10 days. Despite treatment, however, many people with Lyme disease often end up with more serious, widespread infection.
Borrelia burgdorferi: An odd bacterium
The Borrelia burgdorferi spirochete causes most Lyme disease in the United States. At least two other Borrelia species lead to Lyme in the rest of the world. Borrelia burgdorferi is a parasite transmitted by infected ticks from deer, mice, and other small rodents that harbor the spirochete. These animals can have huge numbers of the bacteria and not show any symptoms of disease. Yet when these same spirochetes are transmitted to humans, they cause problems in many organ systems.
Why does the Lyme bacterium affect humans and not the infected animals?
The primary difference is the way the spirochete is transmitted and the way the human immune system reacts to this invader. In humans, the Lyme organism has learned to survive brilliantly.
Evasion starts with invasion
Starting as early as the tick bite itself, Borrelia burgdorferi can evade the best efforts of the immune system in several ways. The tick has certain factors in its saliva that coat the invading spirochetes, protecting them as they enter the body through the skin. This prevents the immune system from “seeing” them. For weeks after a tick bite the immune system of someone infected with Borrelia burgdorferi may not produce antibodies against the bacterium.
Structure is important for evasion
Then there’s the unique feature of Borrelia itself, its flagellum. The flagellum gives the spirochete the ability to cause profound disease. A flagellum is typically an outside tail a bacterium uses to propel itself from place to place. In the Borrelia corkscrew-shaped spirochete, however, the flagellum is located inside the bacteria’s body, somewhat like the skeleton of a snake. The flagellum helps the bacterium invade tissues and thick mucus that would stop most bacteria in their tracks. The flagellum also excites the immune system. Although the immune system can now see the bacterium, it can’t effectively attack it. Instead it launches a massive inflammatory response that ends up damaging surrounding human tissue rather than killing the bug.
Evasion continues with metamorphosis
Once inside the body, the saliva-protected spirochete also starts to change the proteins on its outer cell wall. The immune system typically uses cell wall proteins to detect a foreign invader, develop specific antibodies to fight it, and mount a coordinated immune attack. But the Borrelia spirochete is like a spy who changes his disguise to blend into the crowd. The police have an initial description of the spy, but it’s no longer accurate.
Lyme symptoms and the immune system
The prolonged immune response, trying to fight Borrelia burgdorferi infection, causes most of the symptoms of Lyme disease, including joint inflammation, skin changes, and neurological problems.
Another aspect of Borrelia burgdorferi is that its changing outer proteins further stimulate the immune system. To return to our spy analogy, it’s as if the police know the spy is disguised and somewhere in the crowd. But because they can’t mount a focused attack, they send all available officers to the scene to destroy everything in the environment. In our analogy,Borrelia burgdorferi is the spy and the officers are immune system cells. The environment, unfortunately, is the tissues of the body.
Immune cells that try to fight the invaders include neutrophils, monocytes, macro-phages, and dendritic cells. None are very effective at clearing the infection, but they do wreak havoc when they are in places like joints. Massive numbers of immune cells that invade the joint tissue take up space and release toxic compounds in an attempt to destroy the spirochetes. These cells (particularly neutrophils) release proteins and small molecules such as cytokines, which further stoke inflammation. The result of all this immune activity is joint pain, inflammation, and persistent arthritis. The same principle operates in virtually all organs affected by Lyme disease.
Borrelia burgdorferi in the brain
In the central nervous system, the story is slightly different. The brain doesn’t have the same immune cells that most other body tissues have. In the brain and spinal cord, the de factoimmune system is cells such as astroctyes and microglia. These cells are bad at detecting and eradicating infections. Moreover, they release substances (like quinolinic acid) that can be directly or indirectly toxic to nerves. Similar to elsewhere in the body, they kill human tissue in an effort to kill the spirochete. The infection persists and the brain is damaged as a result of the failed attack.
The unique way that the human immune system responds to the Borrelia spirochete infection causes more problems than it solves. The more that scientists discover about the human immune system and Lyme disease, the better equipped they’ll be to develop treatments that can modulate these painful immune system effects. The ultimate goal of course is reducing orgetting rid of Lyme disease altogether.
