Allergy And Asthma Essay
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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 immunoglobin 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 prostoglandins, 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 subepithelial 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 bronchoconstriction 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. Pateints 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 CD34 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...
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