Role Of T Cells In Asthma example essay topic

The immune system is one of the most complex systems in the human body, it has the ability to recognize and destroy foreign invaders. It can determine foreign from self and can adapt to virtually destroy any antigen. What happens when the immune system is too efficient for its own good? Allergic immune responses are estimated to effect 20% percent of Americans. The word allergy is defined in the dictionary as a hypersensitive state. The hyper-sensitive state is caused by an exaggerated immune response to normal stimuli in our surroundings.

Common stimuli or allergens are pollens, mold, house dust mites, animal dander, and insects (Allernet, 1999). These normal substances stimulate the body to release immuno globin E (IgE) antibodies that are involved in the recognition of these allergens. IgE antibodies on the surface of mast cells are the primary cause of allergies; it is know that these IgE antibodies originated in the body to kill off parasites. Since we hardly ever face attack by parasites, these IgE molecules have focused their attack elsewhere.

Individuals that suffer from allergies most likely acquired them by inheritance from someone in there family. The most common diseases associated with allergies are hay fever, rhinitis, asthma, eczema, contact dermatitis, and urticaria (Allernet, 1999). Asthma is the most widely spread of these diseases and there are 17.6 million Americans who suffer from asthma (Asthma Statistics, 1998). There are 4.8 million children under the age of 18 with asthma (Asthma Statistics, 1998). In order to understand asthma and the effects its has on the human body we must first examine a primary allergic response.

An allergic response is described as a three-step process that involves an initial sensitization to the allergen followed by activation of mast cells and then prolongation of immune activity. The sensitization functions very much like an immune response to chicken pocks. When you first get chickens pocks the immune systems builds up antibodies to eliminate the infection. These built up antibodies remain in your blood stream as an arsenal to ward off future attack. Like the response to chicken pocks the body reacts to the first exposure by building up IgE antibodies to help in a future attack.

The problem is once your immune systems responds to the harmless allergen (Ex. grass) you will then develop a predisposition to this substance. Most likely you will be allergic to grass the rest of your life. Allergy mediations and therapy will be your only option if you plan to go outside. Grass is an also of an allergen that is hard to avoid. I use grass as my example because it is not a seasonal allergy and I am personally allergic to all types of grass. Sensitization begins by an allergen, typically a protein, making its way into the body through several routes.

Usually they enter through the mouth and nasal pathways but they can also enter the bloodstream by means of a scratch or insect sting. Once the allergen enters the body it starts of chain reaction within the immune system that causes the construction of the IgE antibodies. When the allergen enters the body it's first engulfed and degraded by macrophages. The macrophages then present fragments of the allergen that T lymphocytes recognize and bind to. Binding of the T lymphocytes starts the secretion a chemical known as interleukin-4. Interleukin-4 is a chemical that causes neighboring B lymphocytes to mature into plasma cells.

Plasma cells are mature B lymphocytes that are capable of creating and releasing antibodies. In the case of an allergic response these plasma cell form the IgE antibodies, which migrate and attach to mast cells and basophils. Mast cells, which are located close to blood vessel and epithelial tissue, are then ready to promptly react in future encounters with specific allergens. Now that the mast cells are primed we will look at what happens when the immune system later encounters the same allergen. The second stage is usually recognized by the activation of mast cells. It is important to note that in the first stage you will not find symptoms of an allergic reaction.

The symptoms that are normally observed are caused by the activation of these mast cells in your tissues. When the same allergen enters your body for the second time they attach to the IgE antibodies found on the surface of the mast cells. When it attaches to two IgE antibodies it draws together the IgE receptors in the cell membrane of the mast cells which are then activated. When the cell is activated the receptors secrete a variety of enzymes. Enzymes include tyrosine kinase, phospholipase C, protein kinase C and an influx of calcium ions (Chung, 1990). The combination of all these enzymes stimulates granules inside the mast cells to release their contents.

The granules then migrate to the surface of the cell and release prostaglandins, leukotrienes, histamine, and cytokines (Redington, 1995). These chemicals are responsible for the symptoms that appear during exposure to an allergen. Now you understand why the mast cells and IgE antibodies serve as the control behind allergic reactions. The third and final stage is not really a stage but a continuation of the physiological effects of the chemicals secreted by the mast cells.

Chemicals from mast cells cause a prolonged response that stimulates basophils and eosinophils moving throughout the bloodstream to migrate into affected tissues. The basophils and eosinophils are capable of secreting enzymes that can cause damage to tissues thus prolonging response. The presence of a large numbers of these cells in the location of inflammation is another example of the similarities between allergic and parasitic responses. You will never find basophils present at the site of a bacterial or viral infection. They cells are only found at sites of parasitic invasion. Now that we know how an allergic response is triggered in the immune system we can examine the human mast cell and the mediators that it releases.

Human mast cells have the ability to release a wide variety of pro-inflammatory mediators and have a high-affinity receptor for the IgE antibody (Redington, 1995). Its proximity to blood vessels, mucous surfaces and smooth muscles has given it a close association with asthma and other allergic disease (Redington, 1995). Mast cells are most abundant in the lungs and 80% of them are located in the conducting airways (Redington, 1995). Their location further illustrates how they are involved in diseases like asthma. Within the bronchi, they are situated in the sub epithelial connective tissue and between the smooth muscles (Redington, 1995).

Because they are located in the areas of the lungs they are in prime position to respond to allergens in the environment. Mast cells secrete two different types of cellular mediators, preformed mediators found in the granules and lipid or lipid-derived mediators. Preformed mediators consist of histamine, proteoglycans, and platelet-activating factors. Cytokines, leukotrienes, and prostaglandins make up the group of lipid mediators.

Histamine is probably one of the best known of all the mediators associated with the mast cells. Histamine is synthesized in the Golgi apparatus from the precursor amino acid histidine and then is stored in the granules of the mast cells (Redington, 1995). Histamine induces broncho constriction by making the smooth muscles contract around the bronchioles (Curry, 1946). This can cause wheezing and breathing difficulties.

Histamine stimulates nerve endings in you skin and they also cause secretion of mucus in the airways. Patents usually develop rashes because histamine is forcing them to have to itch their skin. Histamine is the main target of drugs such as Zyrtec and Claritin. These drugs are categorized as antihistamines, which means that they prevent the secretion of histamine by the mast cells. Leukotrienes and prostaglandins act similar to histamine in that they increase constriction of the bronchioles and the permeability of small blood vessels. Leukotrienes are derived from arachidonic acid and are produced by leukocytes (Nathan, 1996).

The problem is that leukotrienes are 150-1000 more potent then histamine and can cause bronchial hyperreponsiveness (BHR) to last up to two weeks (Nathan, 1996). New therapies are being used to target the production of leukotrienes. Since they are more potent then other mediators it a good target for drug intervention. Basophils are not always described when talking about allergies but were rather once thought to be precursors of mast cells (Redington, 1995). These cells are similar to mast cells in that they are derived from CD 34 cells in the bone marrow (Redington, 1995). Unlike mast cells basophils do not reside in the tissues but are only recruited into tissues from blood in response to specific stimuli.

They are recruited usually in response to cytokines derived from the mast cells. Basophils solely release histamine and leukotrienes and are important because they are the main suppliers of histamine during late phases of allergic reactions and asthma. Remember that basophils receive express IgE antibodies on their surfaces that were attached during the sensitization phase. If both the mast cells and the basophils have the same IgE antibodies then they are both capable of reacting to the same allergen. They in affect pose a double threat to the site of exposure.

There are several well-known allergic conditions that are associated with people who have allergies. One of them is asthma, which we well cover in depth later, and the other is hay fever. Allergic rhinitis affects 15% of Americans and there are two different forms (Asthma Statistics, 1998). The first being hay fever in which the person has seasonal allergies and react to allergens in the outside world. They usually are allergic to such things as pollens, grasses, and weeds. The other is termed perennial meaning that symptoms are usually caused by indoor allergens, such as dust mites and animal dander.

Allergic rhinitis is never fatal and is more of a nuisance then anything. Doctor usually combat rhinitis with antihistamines. But if antihistamines don t help they will sometimes use corticosteriods to prevent inflammation. Corticosteriods are normally used to treat patients with asthma. Believe it or not allergies can sometimes be fatal. You don t hear a lot about people dying from an allergic reaction but there is on average of more than 5,000 deaths a year from asthma alone (Asthma Statistics, 1998).

Another major threat is what is called anaphylaxis, which results from an acute explosion of chemicals from mast cells. This is a very dangerous situation and a person can virtually die within minutes. Usually anaphylaxis is caused by allergic reactions to foods such as shellfish, peanuts and cod, or to bee and wasp stings. The exposure to one of the above allergens elicits one or more symptoms immediately. The deadly symptoms include swelling of the lips, tongue, and larynx that can cause suffocation. It can cause nausea, vomiting and abdominal cramps, and even potential heart attacks.

Shock is the major cause of death. The best treatment for people who suffer from this condition is to avoid exposure. For people who are allergic to bee stings researchers have developed an immunotherapy to help prevent anaphylaxis. When doing immunotherapy they would expose the patient to a small amount of the allergen in order to slower strengthen the immune system.

How do you know if you have allergies? Doctor's typically use a test called a wheel-and-flare reaction test. What they will do is inject a tiny amount of a certain allergen into your skin. If you are allergic to the substance injected then you will develop an immune response causing a red bump to appear. This test is very crucial in determining what a patient is allergic to. For example if you are allergic to different types of molds, you can use preventative measures to avoid contact.

You might want to make sure that your shower or bathtubs stay free of molds. There are a lot of helpful benefits to being able to identify substance that promote allergic responses. I have personally had this test done and it has helped me to acknowledge and avoid allergens that might cause irritation. Asthma has become an increasing problem with young children showing a 75 percent increase in the number of cases since 1980 (Asthma Statistics, 1998). Asthma is a condition that can be directly linked with allergic reactions. There are two forms of asthma; the first known as atopic (extrinsic) can be traced to a certain allergen that stimulates the production of IgE antibodies.

The second non-atopic (intrinsic) cannot be traced to a certain substance. A person that has asthma suffers from constriction of the airways that intern limits lung function. The first type of asthma can be correlated to the release of histamine by the mast cells. Exposure to an allergen is not the only way to stimulate symptoms in asthmatics. Exercise and cold, dry air can brings on symptoms just as easily as does and allergic exposure. In the mid-1980's there was general consensus that the mast cell was the central structure behind asthma (Kay, 1998).

The leaky mast cells were capable of explaining both the atopic and the non-atopic forms of asthma. It was not till later that they determined that antihistamines had little or no effect on some patients. Researchers begin to realize that even between acute attacks the airways were responsive to stimuli such as methacholine (Kay, 1998). This gave rise to two subdivisions of asthma: acute and chronic. Acute being the normal response to allergens and chronic is characterized by damage to the actual lung tissue. Thus the concept of chronic inflammatory disease emerged.

Advances in the early 1980's soon established that esoniphils and activated T lymphocytes were a feature of asthmatic airways even in the lack of symptoms (Kay, 1998). This gives us reason to look at T cells and the role that they play in chronic asthma. T cells play a direct role in chronic asthma because they control the action of the esoniphils. Esoniphils are cells that are located in the bloodstream especially in the vessels of the lungs.

When stimulated they release enzymes that cause damage to the lung tissue. During acute asthma we know that the T lymphocytes release interleukin-4 which stimulates surrounding B cells to produce IgE antibodies. The difference between acute asthma and chronic asthma is that in chronic asthma T lymphocytes release interleukin-5. Interleukin-5 and Interleukin-3 mobilize and activate esoniphils that in turn promote tissue damage (Kay, 1998). Chronic asthma is more of a problem and is harder to deal with then acute cases. This is due to the fact that chronic asthma is easier set off by vapors and other trace chemicals in the environment.

There are several different therapeutic approaches when it comes to treating asthma. The most common treatment is the use of bronchodilators to help open airways back up. They serve to relieve the symptoms brought on by histamines in the lungs. Bronchodilators are very safe and effective but prolonged use of the same one can cause a rebound effect in the lungs. Asthma therapists will usually prescribe one for a short length of time and then they will switch to another to avoid rebound. There are about four or five different types available and I have been using a Ventolin inhaler for years.

These inhalers are good for immediate relief of wheezing and tight airways. But many doctors will take a more preventive approach to treating asthma. The discovery of corti-co steroids and their effect on the lungs have greatly improved the quality of life for asthma patients. They serve to prevent inflammation of the lungs tissues and the bronchioles. When corticosteroids first came on to the scene there was a fear that they would produce steroid-like affects in the patients. When the steroid is inhaled it eliminates all the side effects of normal steroid use.

Corti co- steroids not only control symptoms and improve lung function but they also reduce asthma mortality. They inhibit the activity and recruitment of inflammatory cells, particularly eosinophils, T lymphocytes, and microphages (Barnes, 1998). These inhaled steroids reduce responsiveness to exercise, fog, cold air, allergens, and inhaled chemicals (Barnes, 1998). A typical brand of inhaled corticosteroid prescribed by doctors is know as Azmacort. Studies have shown that for inhaled corticosteroids to prove effective they must be taken regularly (Barnes, 1998). When inhaled corticosteroids are discontinued, there is a gradual increase in symptoms and airway responsiveness back to pretreatment values (Barnes, 1998).

Clinically is has been conventional to start with a low dosage and gradually increase the dosage till asthma control is achieved. Questions however have developed over whether there is side effects to these drugs when they are administered on a daily basis. There are some risk factors when corticosteroids are used on a daily basis. The problem is that for the inhaled steroids to be effective they must be taken on a regular basis with usually means every day.

Some of the side effects are lose of bone density which can led to bone fractures. Most side effects have been correlated to high dosage use by the patient (Toogood, 1998). Even small medium size dosages have shown to cause stunting of bone growth in young children (Toogood, 1998). Because of the knowledge of these side effects doctors are sometimes cautious when prescribing inhaled steroids for treatment of asthma in young patients.

It seems that young adults are more susceptible to these adverse side effects than normal adults. The most effective way to prevent side effects is to use the least amount that still is effective in controlling symptoms. Exercise induced asthma affects 12-13% of people who suffer from asthma (Nastasi, 1995). The level of activity reached, the intensity sustained, the duration of activity, ant he climatic conditions are important factor affecting the severity of each attack (Nastasi, 1995).

Educational and treatment programs have enabled most athletes to participate in strenuous activity without any significant limitations. Many famous athletes have been diagnosed with exercise induced asthma including Dennis Rodman and Jackie Joyner-Ker see. These athletes have still been able to not only perform at a professional level but to excel. One way to determine how exercise induced asthma affects a patient is by use of a peak flow meter. A peak flow meter is a device that measures lung capacity. It works by taking a deep breath and blowing into a chamber as hard as you can.

Peak flow meters are very effective in keeping track of a patients lung capacity. A patient can use it a couple times a day to determine how their lungs are performing. Allergies and asthma is something that I have dealt with on a daily basis for the majority of my life. I have suffered from atopic asthma from an early age and have tried several different types of inhalers.

The most effective of all the inhalers is the one that I mentioned above Azmacort. It is a inhaled corticosteroids and it virtually eliminated all my symptoms. Because my asthma was brought on by allergens doctors had me not only use Azmacort but also take antihistamines to eliminate any allergic reactions. They also prescribed me bronchodilators to handle immediate symptoms.

Use of both preventive medicine and reactive medicine is a common way to treat people with asthma. I m have been diagnosed with being allergic to cats, dogs, grasses, and molds. Before I came to college I had tough times with my allergies and asthma because my entire life I have had cats. Now that I live away from home, away from the cats, I have been able to take myself off Azmacort and just use antihistamines. I rarely have reason to use bronchodilators and I have to say my quality of life has vastly improved. My knowledge of the fundamentals of allergies and asthma has enabled me to share my experiences with others in hope that I might help them too have an asthma free life.

Journals and Literature Cited Allergies and Asthma 1. All About Asthma, National Pollen Network, 1999 web / Reviewed October 8, 1999 2. Allergy FAQ, National Pollen Network, 1999 web / Reviewed October 8, 1999 3. Asthma Statistics, Asthma in America, 1998 web / Reviewed October 9, 1999 4. Barnes, Peter J., (1998) Efficacy of inhaled corticosteriods in asthma. The Journal of Allergy and Clinical Immunology 102 (4 pt 1): 531-37 5.

Chung, K.F., (1990) Mediators of Bronchial Hyper responsiveness. Clinical and Experimental Allergy 20: 453-58 6. Curry, JJ (1946) The action of histamine on the respiratory tract in normal and asthmatic subjects. Journal of Clinical Investigation. 25: 785-794.7. Durham, S.R., (1991) The significance of late response in asthma.

Clinical and Experimental Allergy 21: 3-7 8. Holgate, S.T., (1991) The mast cell and its function in allergic disease. Clinical and Experimental Allergy 21 (S 3): 11-16 9. Kay, A.B., (1998) Role of T Cells in Asthma. Chemical Immunology 71: 178-91 10.

Nastasi, Kent J., He inly, Tammy L., and Bliss, Michael S., (1995) Exercise-Induced Asthma and the Athlete. Journal of Asthma 32 (4): 249-57 11. Nathan, Robert A., (1996) Anti-Leukotriene Agents: A New Direction in Asthma Therapy. Journal of Asthma 33 (6): 353-66 12.

Redington, Anthony E., Polos a, Riccardo, and Watts, Andrew F., (1995) role of Mast Cells and Basophils in Asthma. Chemical Immunology 62: 22-59 13. Toogood, John H., (1998) Side effects of inhaled corticosteroids. The Journal of Allergy and Clinical Immunology 102 (5): 705-12 Glossary Basophils A type of white blood cell, which can be easily stained with alkaline dyes.

It has a nucleus with two lobes and it carries around substances like histamine and a hormone called serotonin. Contact dermatitis inflammation of the skin caused by something that has been in contact with the skin tissue Cytokines – any of many soluble molecules that cells produce to control reactions between other cells. Eczema inflammation of the skin, usually causing itchiness and sometimes blisters and scaling; may be caused by allergies, but often occurs for no apparent reason Eosinophils A type of granular leukocyte that is an amoeba-like scavenger that disposes of cellular debris. This cell takes its name from the fact that it can be stained with eosin. Histamine An amine with the chemical formula C 5 H 9 N 3, released during an allergic response which causes smooth muscle contraction, inflammation, the secretion of mucus, and other allergy symptoms. Interleukin – Any of a group of protein factors which are produced by T lymphocytes and macrophages (a type of white blood cell) in the presence of antigens.

They cause the T lymphocytes to activate and proliferate. Leukotrienes Any of a group of hormone derived from arachidonate (arachidonic acid). They are thought to mediate the allergic response that causes lung constriction and muscle contraction in asthma. Urticaria an allergic reaction in which itchy white lumps surrounded by areas of inflammation appear on the skin; commonly called "hives'.