What you don’t know can harm you

"Anything that can be eaten will be eaten" was the first statement Dr. Ed Padlan said during our seminar class at the UP Marine Science Institute. Our topic wasn’t about predators and prey in the vast ocean but something more familiar to us – the human body. It wasn’t a seminar course in Marine Ecology after all, but in Molecular Immunology.

It is quite amusing how we can go on with our daily tasks and not notice and feel the "battle" going on inside us. In connection with the first statement I quoted from my professor, it is unfortunate that we are, in a way, food – a source of nutrition and essential for the survival of a wide array of microorganisms. But fortunately enough, our body has defense mechanisms to overcome this attack by preventing the entry or containing the spread of these foreign materials collectively called antigens, once they are able to find their way inside our cells or in the body in general. The immune system, composed of humoral and cellular components, is responsible for our survival despite the ubiquitous presence of bacteria and other pathogens (disease-causing agents). This brings to mind an experiment in our Microbiology class back in college wherein we prepared sterilized agar culture media in petri dishes. We exposed one to the open air, others were made to come in contact with the doorknob, to a money bill, and lastly, with our own hands. It was a total revelation of the presence of bacteria everywhere when several different bacterial colonies were seen in all plates after incubation. It is unimaginable how many of those kinds we will have to come in contact with during our lifetime. It’s a relief to learn what our immune system can do. The humoral arm of the immune system involves antibodies that circulate in the body fluids and specifically recognize antigens such as bacterial and viral components. There are approximately 108 different B cells in one’s body each producing antibodies with different specificities at any given time. Antibodies cross-link with the antigens and form an immune complex that is engulfed by macrophages (a cellular component). Aside from the macrophages, the cellular arm is composed of cytotoxic T lymphocytes (CTLs), and T-helper cells. CTLs target and kill cells expressing fragments of the antigen on its surface. T helper cells direct antibody- and cell-mediated immune responses through the secretion of molecules called cytokines that have important effects on B cells, CTLs and other immune cells. However, despite the sophistication and complexity of our immune system, having been a product of evolution for quite a long time, our body may still lose control and succumb to invaders. Most, if not all, pathogens are continuously evolving by the process of mutation to be able to crack down the defenses of their host, develop a new mode of transmission, and expand their host choices.

Let’s take, for example, the Human Immunodeficiency Virus or HIV, the retrovirus that causes AIDS. The retrovirus’ genetic material is in the form of RNA instead of the usual DNA but it possesses an enzyme called reverse transcriptase that converts RNA to DNA. This allows the retrovirus to use the genetic machinery of the host cell for its own replication. Our immune system initially has the ability to contain HIV infection, as it is able to produce antibodies directed to the HIV. But after some time, the immune system is subverted and the person becomes susceptible to diseases caused by other pathogens, which normally would have been easily regulated by the immune system. The latter signals the onset of AIDS. The progression from HIV infection to AIDS tends to vary between individuals and the HIV strain. How is HIV able to get away from the offense launched against it? It is tempting to believe that there is such a thing as "viral intelligence" as Dr. Padlan would usually refer to it. It is interesting to note that this highly evolved virus seems to be using a very ancient tactic – a successful approach used in the Trojan war of ancient Greece – the Trojan Horse. Integrating the existing data on retroviral biology, researchers from the John Hopkins University composed of Dr. Stephen Gould, Amy Booth and James Hildreth came up with a model of retroviral biogenesis and transmission and called it the Trojan Exosome Hypothesis. An article bearing the same title was published in the Sept. 16, 2003 issue of the Proceedings of the National Academy of Sciences (PNAS).

Exosomes are small membrane bound molecules that are released into the external environment, which fuse with membranes of neighboring cells to deliver membrane and cytoplasmic proteins from one cell to another. Inter-cellular signaling by exosome exchange is important in many physiological processes, including lymphocyte activation and the development of immunological tolerance

Previous models of retroviral transmission assumed that the binding and fusion of retroviruses, such as HIV, to host cells are completely dependent on the retroviral envelope proteins. This is not the case, however, as retroviruses can have many types of host cell molecules and are capable of receptor- and envelope-independent infections. The Trojan Hypothesis states that the retrovirus taps the pre-existing, non-viral pathway of exosome biogenesis and exosome uptake for the formation of retroviral particles and transmission, respectively. As the cells involved in the process of immune surveillance and signaling circulate throughout the body, they are exposed to numerous exosomes, which may be loaded with retroviral particles. As it replicates predominantly in the immune cell population, it is able to evade attack launched by the immune system and at the same time disrupt the host’s response to the infection, thereby enabling continuous replenishment of the virus population.

Despite the tremendous efforts in HIV and human immune system research, an ideal vaccine has not yet been made. This difficulty lies in the HIV’s extraordinarily high mutation rate. This also allows the virus to evolve resistance to the drugs used for treatment. And this is further aggravated by the fact that HIV exploits the immune system designed to stop it and other infections. It is by increasing our knowledge of how the HIV and the components of our immune system interact at the molecular level that an effective approach to combat HIV infection and AIDS may be developed. As Sun Tzu stated in his book The Art of War, "If you know the enemy and you know yourself you need not fear the results of a hundred battles."

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Mary Anne Q. Astilla completed her BS Marine Biology degree at the University of San Carlos, Cebu City. She is currently an M.S. Marine Science student majoring in Marine Biotechnology at the University of the Philippines-Marine Science Institute. E-mail her at [email protected]