Tuesday, July 19, 2011

Human Immune System’s Defense Against Anthrax Infections


Recent studies have revealed that the human body’s immune system has its own self-defense mechanism against the anthrax bacterium, Bacillus anthracis. The findings suggest that the body sends out emergency signals when it is faced with a deadly infection.

Bacillus anthracis
is a rod-shaped, Gram positive, aerobic bacterium that causes the anthrax disease. B. anthracis produces spores that can survive for years. Anthrax is a disease that mainly infects animals that ingest or inhale the spores while grazing on soils that are contaminated; however, in rare cases, anthrax can affect humans who come into contact with infected animals or animal products. Ingestion, inhalation, and skin contact are ways that anthrax can enter the human body. Once the bacterium is inside the body, it spreads from the tissues to the lymphatics. B. anthracis specifically targets immune cells, called macrophages, that protect the body from infection. The bacterium then produces two very powerful exo-toxins and lethal toxin that causes rapid cell death. If left untreated, the body’s immune defenses could collapse, which would allow the bacteria to reproduce and eventually cause septic shock and rapid person death.


The researchers at the University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences have discovered the macrophages that are initially infected by the anthrax bacterium, immediately send out signals to other immune cells as a defense-mechanism. Adenosine triphosphate (ATP) is the actual molecule that macrophages use in order to communicate with the other immune cells during this survival strategy. Michael Karin, PhD, distinguished professor of pharmacology and senior author of the study, said, “The warning alarm sounded during anthrax infection is elegant, complex and can be effective in slowing spread of the pathogen.” According to Karin, ATP that is released from the initial infected macrophage is sensed by a second macrophage. The second macrophage triggers the molecule inflammasome, and, in turn, inflammasome then releases a molecule called interleukin-1beta (IL-1beta) into the bloodstream. IL-1beta warns other macrophages to strengthen their resistance against cell death caused by anthrax.


The researchers performed a series of experiments, involving the use of genetically altered mice or inhibitor drugs, in order to confirm the significance of this molecular circuit. Several different results were discovered when the researchers interfered with the ATP channel, the ATP receptor, inflammasome or the IL-1beta molecule; the macrophages were not able to survive, there was unimpeded growth of the anthrax bacteria, or there was rapid death of the anthrax-infected mice. The researchers also concluded that only the most dangerous bacterial pathogens caused a response in the immune response pathway.


Victor Nizet, MD, professor of pediatrics and pharmacy said, “We hope these findings can be exploited for the design of new treatments to help the body combat serious bacterial pathogens. Supporting the survival of macrophages and preserving their immune function may buy patients precious time until antibiotic therapy is brought on board to clear the infection.”


References:

University of California - San Diego. "How the immune system fights back against anthrax infections." ScienceDaily, 17 Jun. 2011. Web. 18 Jul. 2011.

http://en.wikipedia.org/wiki/Anthrax

http://www.dhpe.org/infect/anthrax.html

http://scopeblog.stanford.edu/2011/06/human-immune-system-has-developed-elegant-self-defense-against-anthrax-infection/

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