On February 14th, 2002, I lost the ability to move everything from the shoulders down, in an hour. Eventually, though the onset was atypical, it was determined I had multiple sclerosis (MS). It’s coming up on four years this winter, and I am still getting around in a motorized wheelchair. Having MS certainly does one thing for you: it makes you want to know more. Research is being done on just about every possible avenue when it comes to MS. One thing is pretty much set in stone, though, when it comes to this disease. MS has definable links with various aspects of the immune and nervous systems that allow for autoimmunity to occur.

MS is an autoimmune disease where the body’s defense system attacks the central nervous system (CNS), resulting in varying degrees of disability. Though no definite test yet exists to pinpoint MS, there are several key symptoms that are associated with it. The National MS Society website notes the symptoms of MS vary, but the more common ones are bladder problems, walking and balance difficulties, numbness, fatigue, vision issues, and plasticity (“Symptoms”). Since MS is so varying in its onset and progression, the medical community has categorized the disease into four different types. The Neurology channel website acknowledges that “Multiple sclerosis is classified according to frequency and severity of neurological symptoms, the ability of the CNS to recover, and the accumulation of damage” (“Overview”). The types are primary progressive, relapsing-remitting, secondary progressive, and relapsing-progressive (“Overview”). Medications are prescribed for treatment, along with rehabilitation and drugs to deal with the side effects of the disease. Avonex, Rebif, Betaseron, and Copaxone are four medications given by injection that affect the progression of the disease (“Treatment”). Corticosteroids, which Venes defines, are both made by the body naturally and synthetically produced for medicinal uses, and are used during the worsening of symptoms or relapses (“Corticosteriods” 474; “Treatment”). Treatment also includes various therapies like physical, occupational, and sometimes even speech in order to deal with the disabilities that can occur with its progression. The disabilities that can arise are due to the attack of the immune system on the body.

The nervous system bears the brunt of this disease, and the area typically affected and which causes the most noticeable disability is the spinal cord. Clayman explains that the central nervous system is considered to be the brain, spinal cord, and neurons, which are nervous system cells that make both of these (60, 62). The spinal cord is like a highway for both voluntary and involuntary orders from the brain to do things in the body. The CNS connects with what is known as the peripheral nervous system and together they help us do things like walk, think, or remember (Clayman 60-61). Freeman mentions that the nervous system is also involved in things you might not think of, like the regulation of how fast the heart beats, bladder function, pupil dilation and restriction in the eyes, and the release of glucose, a sugar which is processed into energy (821). The neurons, which allow for electrical signals to be sent through the spinal cord, have arm-like structures known as axons and dendrites (Clayman 62). Dendrites receive signals from other neurons while the axons send them to wherever they are supposed to go (Clayman 62-63). The axons can be thought of as an electrical wire, and often wires have insulation around them that protects the electricity from escaping. Well, axons have something known as myelin sheaths that protect them and allow for ease of transmission of electrical signals (Clayman 62). The nervous system has cells that support it; known as neuroglia, these cells can be astrocytes, oligodendrocytes, Schwann cells, and microglia among others (“Neuroglia” 1383). Oligodendrocytes are important, as they are responsible for generating the myelin to protect the nerves. Another system in the body that is heavily involved in MS is the immune system.

A healthy immune system has several factors that work together to defend the body against foreign materials or invaders. The system can be broken down into two parts, the innate immune response and the acquired immune response (Freeman 892). The innate response is ready at any time while the acquired immune response involves activation before it can aid in defense (Freeman 892). The acquired immune response is characteristic of cells known as lymphocytes, which are moved through the lymphatic system and the blood to aid in the body’s defense (Clayman 124-125). Lymphocytes are a white blood cell and can be broken up into three groups: B cells, T cells, and natural killer cells (“Lymphocytes” 1221). Lymphocytes fall under the broader category of leukocytes; these are white blood cells and can also be neutrophils, macrophages, mast cells, and dendritic cells among some others (“Leukocytes 1171-72; Freeman 904). The dendritic cells are involved in the processing and activation of T cells with the major histocampatibility protein (MHC) (Freeman 904). Basically the dendritic cell takes in a antigen, which “is any foreign molecule,” processes it into a MHC-antigen complex, and then presents it so T cells can interact with it (Freeman 892, 904). The MHC protein is attached to the process’s piece of antigen and displayed in the outside of the dendritic cell. MHC can be divided into two types, the MHC class I and MHC class II. It’s through this interaction that the acquired immune system lymphocyte T cell is activated, multiplies, and turns into other types of T cells, such as helper T cells and cytotoxic T lymphocytes (Freeman 904). The helper T cells can be broken down into two subtypes, helper T cell 1 (Th1) and helper T cell 2 (Th2). Hormones are a type of molecule that is released into the body to illicit effects on various things such as organs and cells, and immune cells also release molecules for the same type of purpose.

Different cells involved in the immune system secrete hormone-like molecules that influence responses from the body. Marc Feldmann, from the Kennedy Institute of Rheumatology in London says cytokines are “protein mediators involved in cell growth, inflammation, immunity, differentiation and repair” (719). Though they are not just involved in the immune system, they do play a key role in it. Like the lymphocyte T and B cells, most cytokines are only produced after activation, and their range of effect is very close to where they are released (Feldmann 720). Some of the important cytokines that will come into play with MS are: interleukin (IL)-1?, IL-3, tumor necrosis factor (TNF)-?, interferon (IFN)-?, IL-6, IL-10, IL-12, IFN-?, and TNF-? (Feldmann 721). The definition for interleukin is “a type of cytokine that enables communication among leukocytes and other cells active in inflammation or the specific immune response” (“Interleukin” 1067). Interferons are proteins and are involved in “antiviral activity” (“Interferons” 1066). The tumor necrosis factors mentioned are produced mostly by T cells and macrophages, and are involved in the immune response as regulators (“Tumor Necrosis Factors” 2164). Chemokines, a type of cytokine, attract cells like neutrophils and T cells which are involved in destroying foreign elements in the body (““Chemokines” 377). Hans Link and Bao-Guo Xiao, from the Division of Neurology at Huddinge University Hospital in Sweden, say that “Transforming growth factor ? (TGF?) is a cytokine produced by a multitude of cells, including T and B lymphocytes and macrophages” (2392). This particular cytokine has been found to function with immune suppressive actions. For the immune system to work normally there must be a balanced system between pro-inflammatory and anti-inflammatory molecules, and TGF? is one of those regulatory molecules. It’s when these balances get thrown off that problems can arise as is the case with MS.

The immune system has safe guards to ensure self tolerance, but in some cases, as with MS, autoimmunity can develop. The definition of autoimmunity is “the body’s tolerance of the antigens present on its own cells” (““Autoimmunity” 194). Allergies and asthma are both autoimmune reactions in the body; however, the autoimmune diseases take things one step further. If your immune system didn’t have a type of safe guard in it, then it could very well start attacking normal cells that are in the body. Peter J. Delves, from the Department of Immunology at University College London Medical School, reports that it has ways of recognizing “self from nonself” antigens and eliminating those destroying cells that pose a risk towards autoimmunity (293). Evidence has even been found through scientific studies, like the one performed by Waldner, Collins, and Kuchroo, that the cells that present antigens on their surfaces (for example, dendritic cells) “can break self tolerance and trigger the development of autoimmunity” (990). Autoimmunity, as you might guess, is tied closely with autoantigens, which is what the cells that cause destruction (like T cells) are attracted to and consequently cause damage to the tissue presenting it (“Autoantigens” 193). When the body starts presenting this type of antigen, autoimmunity and autoimmune disease are most certainly involved. Autoimmune diseases come in a variety of forms. Ian R. Mackay, from the Department of Biochemistry and Molecular Biology at Monash University in Australia, lists a few that are fairly well known: Graves’ disease, MS, rheumatoid arthritis, and possibly psoriasis (288).

MS is considered a neurological disease when it comes to autoimmunity; it, along with other disorders of this type, happen when, as A. Vojdani, E. Vojdani, and Cooper explain, “tolerance to myelin and other neurological antigens of Schwann cells, axons and motor neurones [sic] are lost” (363). The problem with MS and the idea of autoimmunity is that researchers have a limited understanding of everything that is going on to cause them. Konrad Schauenstein, from the Institute of Functional Pathology in Austria, states that with autoimmunity, the T cell has been targeted as an area of interest since it aids in a regulatory capacity (275). The MHC proteins that aid in presenting antigens for activation of the T cells also seem to play a crucial role. Though the exact process still remains elusive, it’s thought that the MHC molecules can in error present an autoantigen (Schauenstein 277). This in turn activates the T cells along with other cells like macrophages which are capable of destroying things within the body (Schauenstein 277). They accomplish this by releasing cytokines like IL-2, IFN-?, TNF-?/?, and others (Schauenstein 277), which leads to the consequent destruction of the whatever tissue the autoantigen came from (Schauenstein 277). With the concept of normal functions for the immune system, the parts of the nervous system they effect, and the idea of autoimmunity covered, we can now make the connections between MS specifically and all these processes.

With MS, you can easily look at the way the immune system functions and describe it as overactive. The types of cytokines associated with the debilitating effects of this disease are the ones of pro-inflammatory nature. It is well known that low levels of vitamin C in someone’s body can lead to scurvy, and too much of something also can develop into other various problems that render us unhealthy. C. S. Chiang and associates observe that IL-3, which is involved in activation and gathering of macrophages and microglial cells, in low levels is associated with demyelination (1512). Microglial cells, by definition, are “Cells of the central nervous system (CNS) present between neurons or next to capillaries. These cells may function as macrophages when they migrate to damaged CNS tissue” (“Microglial Cells” 1294). Macrophages, like T cells, are responsible for destroying foreign things within the body as part of the immune system. F. Ensoli and fellow researchers affirm that some cytokine factors which are shown to be increased in MS patients are INF-?, TNF-?, and TNF-? and these are all associated with the lesions or areas of myelin destruction (284). L. G. Filion and company add that also associated with MS lesions are a host of other cytokines like IL-1, IL-6, IL-10, and IL-12 (324). IL-12 in particular, which is produced by monocytes, a type of white blood cell similar in function to macrophages, is associated with how severe MS presents itself (Filion et al. 324).

Z. A. Erkut and fellow researchers emphasize that while IL-1, IL-6, and TNF-? are implicated with roles during relapses of MS, and IL-4 and IL-10 are considered tied with times of remission (229). The ramifications of this disease are plentiful and severe, but there are some ways to fight against it even though a total cure has yet to be found.

By investigating naturally what the body does in response to factors in MS, treatments have been formulated to aid in the reduction of relapses and their severity. INF-? is commonly used because it “suppresses the expression of MHC class II and production of IL-12 by macrophage and microglial” (Kato et al. 651). TGF-? can be secreted by T cells and macrophages, among others, and is considered a cytokine (Link and Xiao 2392). As A. P. Kuruvilla and company, along with Link and Xiao, note, it has immunosuppressive qualities as it is credited with regulating the production of cytokines like IFN-?, IL-4, IL-1, and TNF-? (2918; 2396). All the main factors attributed to MS and its disability like IFN-?, IL-1, and TNF-? are controlled, which is good, but so is IL-4, which is associated with remission points in the disease. IFN-?, the widely used synthetic treatment for MS, also has this dual effect in that it increases production of TNF-?, IL-1?, and NO which are thought to be the cause behind the flu-like side effects from taking this medication (Kato et al. 657-58). Cytokine involvement in MS has been pretty much solidified through research and the evidence accumulated during research, but the cells involved in cytokine production also come into play.

A number of cells secrete cytokines into the body, but certain specific ones are involved in the immune system and are tied to MS. The immune system cells, in a way, work together with the cytokines they produce to aid in the progression of the disease. A major player has been identified as partially responsible is the T cell. There are various kinds of T cells: the killer cells are involved in the attacking and destruction through the release of cytokines, helper cells are involved in the activation of B and T cells, while suppressor cells, as can be derived from their name, suppress other cells from responding to antigens (Clayman 127). What’s interesting to note is that two of these T cell types can be associated with MS. The killer cells could be involved in the myelin destruction and the helper cells in activating the killer cells to attack the myelin. Proinflammatory cytokines released from cells like T cells are thought to be identifying marks of disease activity while anti-inflammatory cytokines are associated with remission. The T cells not only release cytokines that are harmful to the body in an autoimmune environment; they also release ones capable of inducing other cells to release other detrimental molecules as well. Researchers note that “monocytes primed by T-cell-derived IFN-? to release TNF-? and TNF-?, have been reported to be injurious to myelin and oligodendrocytes” (A. Vojdani, E. Vojdani, and Cooper 364). Monocytes are a white blood cell involved with macrophages in the initial defense of the body against foreign invaders by attacking and destroying those (“Monocytes” 1315).

Macrophages, which are also involved in attack and destruction in the immune system, have been implicated with a role in MS. “Along with neutrophils, macrophages are the major phagocytic cells of the immune system” (“Macrophages”1227). However, outright destruction is not their only function, and it is just another reason they are suspect in MS. Like dendritic cells, which are a lymphocyte like macrophages, they “also serve a vital role by processing antigens and presenting them to T cells, activating the specific immune response” (“Dendritic Cells” 1227). It’s easy to see how these processes, which in most people serve as a life-saving purpose, can be turned into the instigator in a disease like MS. Microglia, which are cells found within the CNS, can act as macrophages when around damaged areas within the CNS (“Microglia” 1295). The article titled “Weapons of Sheath Destruction,” along with researchers Loughlin, Woodroofe, and Cuzner, reports that these cells have been observed to be involved in the harming and destruction of oligodendrocytes and the clean up of debris within the CNS (125). This is important as it implicates microglia in furthering the progression of the disease. The lesions, a classic sign found in MS patients, are spots in the nervous system that have been damaged. Though it’s possible that microglia are also partly responsible in the actual damaging process, they have positively been noted to be “packed with myelin debris” within the close vicinity of lesions from MS (Loughlin, Woodroofe, and Cuzner 125). As can be expected, microglia also produce cytokines that can be harmful under certain circumstances, like in MS. M. Yoshikawa and associates list that among these are TNF-??, IL-1, IL-5, IL-6, IL-10, IL-12, and TGF-? (126). What is also important to draw attention to is that both proinflammatory and anti-inflammatory molecules are produced. Like the use of synthetic IFN-? as a medication, which in the process of helping to lower the intensity and regularity of relapses also upregulates the production of some of the harmful cytokines involved in MS, trying to suppress microglia can be both beneficial and somewhat detrimental. The cytokines, which both microglia and macrophages produce and which are thought to aid in demyelination, are good candidates for suppression and in theory would relieve the symptoms of MS (Kato et al. 651). These three types of cells are thought to be responsible for the damage inflicted on the nervous system, but what is also important are the variables which are being affected by these cells and the molecules they produce.

Myelin and myelin-associated molecules are a key factor in MS and the disability that goes with it. It is well established how important oligodendrocytes are in regards to the nervous system: “Oligodendrocytes are the cells responsible for myelin synthesis and assembly around axons in the central nervous system” (Molina-Holgado et al. 493). The unique thing about oligodendrocytes is that they can in fact repair myelin; it is an incredibly slow process but it can be done. In the body, certain cells are regenerated easily, like skin cells or the cells lining the digestive tract. However, some cells like cardiac cells and neurons cannot be regenerated. Damage to these cells is permanent and naturally the body is unable to generate replacements. The number of heart and neuron cells you have when you are born is all you have to work with. With MS, however, certain cytokines have been linked to the harming of oligodendrocytes, not just the myelin itself. Benoit Fellay and colleagues note that TNF-?? and IL-1? have been implicated in the destruction of oligodendrocytes (383; Kato et al. 657). The harming of the oligodendrocytes doesn’t induce the disability in MS but does impede the recovery. It’s easy to make the connection between how long it takes for myelin to be regenerated and the lower number of oligodendrocytes capable of doing the work in someone who has MS. On a positive note, though, some factors can improve what seems to be a dismal situation when it comes to the oligodendrocytes. Robert D. Hollifield and company say that TGF-?1 is thought to decrease the production of proinflammatory cytokines and consequently protect the oligodendrocytes (134). Anti-inflammatory cytokines are also credited with being beneficial. The inhibition of cells that can be harmful in the course of MS encourages the continued remyelination by oligodendrocytes; Il-10 in particular is associated with damage reduction and repair enhancement (Molina-Holgado et al. 501).

On the horizon when it comes to MS treatment is the research and possible application of stem cell therapy. As is probably familiar with most, when an egg and sperm come together an embryo is eventually formed. The sperm and egg each contain half a full set of DNA from the contributors, which combine to make up the regular set found in healthy humans. So provided that development occurs normally, what began as a tiny sperm and egg in nine months or so will grow into a baby. What is less well known is how this occurs and it begins with DNA. Every cell in your body has DNA that codes for everything that was needed to make you who you are today. Provided there are no mutations or other problems, the DNA combined from your parents is used to create every cell in your body and, through other processes, place them where they are supposed to go. In one of the very early stages, these cells haven’t been informed of what they will eventually turn into, and it’s at this point that you are referring to embryonic stem cells. There are other types of stem cells, and they aren’t just there when you are still in your mother’s tummy before birth. They have umbilical cord stem cells, bone marrow stem cells, and they can be found in various points in the body for the regeneration of other cells. The difference with stem cells found in adults versus those found in the embryos is their ability to be turned into any type of cell. For instance, the stem cells found in bone marrow can become bone, red blood cells, or white blood cells, but they wouldn’t necessarily be capable of becoming neurons. Stem cells are not only being looked at for people with MS, but also for those with spinal cord injuries and numerous other diseases like Alzheimer’s.

Today the debate rages on and will continue to as the race for stem cell therapy continues around the world, but I think there’s another side that people need to know too.

Merlin Curry, a colleague of mine, mentioned that “most importantly finding the ‘bleeding edge’ and pushing for more research” were two things I’d want to try to do with this paper. Stem cells are what I’m pushing for, and this is why. On Valentine’s Day in 2002, I woke up and in an hour lost my independence, my ability to walk, and, for the time-being, my dignity. By that evening I was laying immobile in the Intensive Care Unit at Kaiser Sunnyside Hospital with two tubes down my throat and a machine breathing for me. I spent the next three months of my life in the hospital. I got out in early May, in time for my twentieth birthday. It’s coming up on four years now, and I’ve had one relapse since. I had regained the ability to walk, stand for long periods of time, to almost do stairs on my own with little help. One relapse, and now I can’t do any of those anymore. I read in my National Geographic magazine about a man who had MS, and they harvested stem cells from his own bone marrow and released them into his body. He was confined to a wheelchair without the ability to walk. Now he can walk again, and all physical signs of the disease are gone. On Wednesday August 3rd, I had a neurology appointment, just a standard check-up with my doctor. I mentioned the story, the treatment, and my doctor could only offer his apologies. Even though it would just be using my own bone marrow, no one he has contact with around here will do it because of the political situation. Right now, my chance to walk again isn’t allowed because the government won’t fund it. I just turned 23 this summer, and I am one of those “bleeding edges” that Curry mentioned. I’m giving a call for research so that I have the possibility of running once more.