Recently, I spent several weeks hiking around the majestic mountains and beaches of New Zealand’s south island. To my better judgment, I avoided any bloodcurdling ‘extreme sports.’ Aside from a four day bike trip and a two day kayak adventure, I mostly hit the trails on foot in various national parks. It was such an incredibly gratifying experience. Part of what contributed to its delight was the absence of poison oak littering the forest floors. I could navigate a small ungroomed trail or even venture off the trail into the woods without the constant anxiety of incidentally brushing against poison oak.
Poison oak, a widespread deciduous shrub found throughout California below 5000 feet in elevation, produces an oil called urushiol that contains a mixture of similar organic compounds. This oil is highly allergenic to hypersensitive folks like me (Wayne’s world website). Urushiol resides in the plants of the Toxicodendron genus, which includes poison oak, poison ivy, and poison sumac, as well as in other closely-related plants in the Anacardiaceae family such as in the skin of mangoes and cashew nut shells (Wayne’s world website). Once the oil touches the skin of a sensitive person, it can take days or even weeks for a highly irritating and blistering rash to fully develop; this is called contact dermatitis (dermatitis means inflammation of the skin). What’s worse is that the compounds are incredibly stable and long lasting such that they will stimulate a skin reaction years later if not washed off articles of clothing with soap and water (Poison Ivy, Oak, and Sumac Information Center). To identify the plant would be an obvious approach to prevention, however, poison oak masquerades as a seemingly innocuous plant (at least to me) and appears to have more than one morphological manifestation that I can never distinctly remember. Sometimes it grows like ivy; sometimes it grows like a bush.I fearlessly hiked the trails of New Zealand, knowing I was in no danger. But, what would I do once I returned to California, a breeding ground for poison oak, ending this period of impunity? What happens when I accidentally eat mango again? Shouldn’t there be a vaccine for this problem? And, this got me thinking about allergies and a possibility for a poison oak vaccine.
With allergies, our bodies perceive non-threatening foreign biological molecules as if they were threatening like a bacterium or virus. How does this happen, and why does this happen so frequently in the population especially regarding poison oak? Approximately 80-90 percent of adults will get a rash if they are exposed to even the smallest bit of urushiol, in this case 50 micrograms (Epstein et al, 1974). In order to understand how things go wrong in our bodies, it’s important to first learn how things work. My knowledge of immunology is woefully inadequate, so I picked up a copy of In Defense of Self by William R. Clark at the library. I highly recommend it to anyone interested in learning about our immune system and its inherent problems such as autoimmune disorders and allergies. Clark masterfully goes into detail on the subject while maintaining wider audience accessibility and curiosity - a craft not bestowed on every writer of complex science topics. I also really appreciate how he infuses a bit of an historical perspective by paying tribute to scientists for their seminal discoveries that advanced the field of immunology. What I learned is fascinating....
Our immune system: a beautifully complex and coordinated defense system
Our immune system is a highly complex molecular police force that “serves and protects” our bodies from hostile takeovers by microorganisms such as bacteria, viruses, or parasites. We absolutely could not survive without it. Within our immune system, there are two coordinated yet functionally distinct responses (or police departments, if you will): the innate immune response and the adaptive immune response. The innate immune response is our first-time responders - they are a group of scavenging cells constantly out patrolling our bloodstream, looking for foreign cells or molecules of biological origin, otherwise known as pathogens. The scavenging cells quickly identify pathogens through a general mechanism (e.g. cell wall components of bacteria) and immediately gobble them up. They also emit chemical signals into the bloodstream leading to the increase of blood flow to the area of infection in an oftentimes painful process known as inflammation. One of these chemical signals is histamine which is released by the large mast cells, one type of scavenging cell of the innate immune response. Anyone who has ever taken antihistamines (e.g. diphenhydramine or Benadryl) to reduce inflammation from an allergic reaction may recognize the name.
While the innate immune response is the brawn of our immunological police force, the adaptive immune response is the brain. Although the adaptive immune response takes longer to turn on its full-blown reaction to pathogens, it certainly provides specificity and memory that’s lacking in its faster partner. B cells and T cells, which comprise the adaptive immune response, remember exactly which pathogens it has encountered through the recognition of biological structures unique to each pathogen. These pathogenic fingerprints, or antigens, are detected with the aid of specialized proteins called antibodies (or antibody-like proteins called T cell receptors, but I’ll get into that later). Only one antibody recognizes one antigen. So, how do they do it? Antibodies stick out of B cells like Y-shaped appendages, surveying cells or molecules as they swim by in proximity (Note: B and T hang out in the lymph nodes and spleen, acting like security guards at checkpoints). An antibody only makes a correct identification when the three-dimensional shape of the antibody perfectly matches that of the antigen, like a hand in a glove or a key in a lock. Well, to be perfectly honest, this perfect pairing is also dictated by complementary chemical interactions, but I won’t quiz you on that. Once a match is made, the B cell becomes activated, launching a massive production of identical antibodies destined for the bloodstream. This army of antibodies tracks down the intruder via its antigen or fingerprints and marks it for destruction. The activated B cell also divides into more identical B cells with the same antibody (called memory B cells) for a quicker, more efficient defense against the pathogen should it re-attempt invasion in the future. This type of memory-generating immunity is called adaptive immunity and is a distinctive feature of vertebrates made possible by the incredible diversity of antigen-recognizing antibodies. By the way, if you’re wondering what happens to a B cell with an antibody that never recognizes an antigen, they self-destruct after one week. The antibody never to be regenerated!
Now, onto the other branch of the adaptive immune response: the T cells. T cells have variable antigenic receptors that bind to and recognize antigens just like antibodies, however, unlike antibodies they require the antigen specifically anchored to a type of scavenging cell called an antigen presenting cell. Once a pathogen enters the body, antigen presenting cells ingest the pathogen breaking it up into smaller components. These cells eventually display these pathogenic bits on their cell surface like a tag (with the aid of specialized anchor molecules called major histocompatibility complex or MHC). Antigen presenting cells such as dendritic cells are primed for invasion as you mostly find them hovering around epithelial tissues like the skin, gut, and lungs. They eventually circulate through the bloodstream to the lymph node security checkpoints where T cells remain vigilant. T cells scan these antigen presenting cells for antigens that match their receptors (much the same way as with B cells and antibodies) and become activated once a match is made. T cells come in two flavors: helper T cells and killer T cells. Activated helper T cells in turn activate both B cells and killer T cells. They also divide to make memory cells with the same antigenic receptors so that, like the B cells, they will be able to launch a faster, more efficient attack against a reappearing pathogen. Killer T cells identify foreign cells such as those infected with viruses and destroy them.
Poison oak-contact dermatitis: a T cell-mediated immune memory response
The following information was gleaned from Wayne’s world
The overreactive inflammation of the skin that happens over the course of several days or weeks in response to the Toxicodendron resin is called delayed-type hypersensitivity. Delayed-type hypersensitivity is different from other hypersensitivity reactions, such as anaphylaxis from peanuts (immediate hypersensitivity) or autoimmune diseases like lupus, in that it is not mediated by antibodies of B cells but rather by receptors of T cells. Thus, it is referred to as a T cell-mediated immune memory response.
In one’s initial exposure to poison oak, urushiol may adhere to the skin where its organic compounds bind to proteins attached to the outer membranes of skin cells. Antigen presenting cells such as dendritic cells misidentify these skin cells marked with urushiol compounds as foreign and so they quickly engulf and digest them. This inherent ability of urushiol to bind to and disguise the skin cells as foreign in the eyes of our immune system is probably why so many of us are allergic to poison oak. The dendritic cells then attach the partially digested urushiol molecules to its surface and migrate to nearby lymph nodes. A helper T cell in the lymph node recognizes the urushiol tag on the dendritic cell through its receptor, initiating the cloning of memory T cells.
After subsequent exposures to poison oak, memory T cells with urushiol receptors may encounter and bind to new urushiol compounds bound to a dendritic cell. The memory T cells then produce even more clones and signals for a backup army of white blood cells including scavenging cells and killer T cells. This army of cells unleashes an arsenal of enzymes and toxins which destroy urushiol-marked skin cells as well as other neighboring skin cells, invariably producing a blistering rash. Fluid from the blood vessels and lymphatics ooze from the skin filling up the blisters, and inflammation makes the skin increasingly red.
Is there hope for poison oak immunity?
“One promising area of desensitization research involves oral pills and intramuscular injections of related or modified urushiol: a molecule similar enough to urushiol to have the same immunological effect, but different enough to avert its excruciating side effects. Several compounds have been used successfully with laboratory animals (Stampf et al, 1986). Future research currently underway may lead to a vaccine that blocks the specific urushiol T-cell receptor and immunizes "high risk" people against urushiol for periods of time (Stampf et al, 1990). In fact, Allergene, a biotech company in San Mateo, California, has successfully produced a hybridoma (fused lymphocyte and carcinoma cell) that makes urushiol-binding monoclonal antibodies. These antibodies prevented sensitized mice from reacting with urushiol and may eventually be available in a serum for people.” From Wayne’s world
As it turns out, the vaccine of modified urushiol compounds proved unsuccessful, mostly because it either didn’t provide immunity or it caused extremely negative reactions in patients. This makes sense as one would expect a T cell-mediated immune response if the modified urushiol molecules are still recognized by the T cell receptors. A serum against urushiol compounds (antiserum) would be nice, but not ideal as it can only be applied following a very recent exposure. It is an example of passive immunity, where antibodies are generated from an outside source. Although effective the first time, antiserum from one animal cannot usually be reapplied to subsequent allergic episodes as the body will generate antibodies against the species-specific serum proteins leading to a greater hypersensitivity in the future (In Defense of Self, William Clark). Lastly, vaccines that inhibit the actions of urushiol T cell receptors seems the most promising and less symptomatically problematic. The vaccinated individual would make antibodies that attack the T cells programmed for urushiol molecule activation rather than the urushiol molecules themselves, thus preventing a hypersensitive reaction. Sadly, searches for any recent information regarding this potentially exciting product came up empty.
So, it seems there is still much progress to be made in finding a solution to our poison oak woes. I am hopeful, especially as we learn more about the workings of our immune system and its foibles. In the meantime, however, I may relocate to the friendlier forests of New Zealand.
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