immune system diagram

The Immune System & Lupus Lyubov Korolchuk Bunsree Patel Topics in Medicine and Biology Summer Ventures in Science & Math Instructor: Willson Kwok July 14, 2006 Abstract: The body has a system of defenses known as the immune system. The immune system has many parts that work together to protect the body against viruses, bacteria, micro-organisms, parasites, and other foreign bodies. Lymphatic organs and leukocytes each have their own role in fighting off invaders of the body. There are two types of leukocytes: phagocytes, which ingest and destroy foreign matter, and lymphocytes, which consist of B-cells and T-cells that regulate the two immune responses: cellular and humoral. When problems arise with the immune system because of non-self/self recognition breakdown, allergies, and excessive response, disorders arise. This paper also discusses Lupus, an autoimmune disorder, which affects all parts of the body. In Lupus, the immune system loses its ability to tell the difference between foreign substances (antigens) and its own cells and tissues, making it a serious and life-threatening disease. Introduction to the System: The immune system is a complex and intricate network of many organs and cells that work together in combination to defend the body against infection, disease, and foreign substances. It can be stimulated in specific ways to fight specific health challenges, which includes fighting off millions of bacteria, microbes, viruses, toxins, cancer cells, and parasites. The organs of the immune system, which are spread throughout the entire body, are called the lymphatic organs (Wikipedia Immune System, 2006). The Human Body’s Lines of General Defense: There are three lines of defense for the human body. The first line of defense consists of surface membrane barriers such as the skin. The skin, which has an acidic pH, is a passive physical barrier to foreign materials such as bacteria and viruses. The skin glands secrete chemicals to inhibit bacterial growth and organisms that live on the skin’s surface are unable to penetrate through. Moreover mucous membranes in the respiratory, digestive, reproductive, and urinary tracts secrete mucus to form an additional barrier. The mucus in the digestive and respiratory pathways traps micro-organisms while the mucosa of the stomach produces hydrochloric acid (HCl) and has protein-digesting enzymes (Farabee, 2001). The second line of defense is the inflammatory response, which is triggered when body tissues are injured. There are four cardinal signs of inflammation: redness, heat, swelling, and pain, which result in a chain of events that lead to defense and healing. The inflammatory response helps prevent the spread of infectious and harmful agents, it removes cell debris and pathogens, and helps set the stage for body repair (Marieb, 2003). The third line of defense is a specific response known as the immune system. It is antigen specific, which means it recognizes and acts against particular foreign substances. In addition it is system and is not restricted to the initial infection site, and has memory, which aids in a stronger attack on previously encountered pathogens (Marieb, 2001). Parts of the Immune System: Throughout the entire human body, the parts of the immune system each have their own role. The bone marrow is the site of origin for all the cells of the immune system including red blood cells, white cells (neutrophils, lymphocytes), and platelets, which are formed and then released into circulation. These cells form through a process called hematopoiesis, where bone marrow-derived stem cells differentiate into either mature cells or into precursors of cells that migrate out of the bone marrow to continue their maturation elsewhere. In the thorax, the thymus gland is responsible for the maturation of new lymphoid cells before they are released into the bloodstream. This maturation process allows T cells to develop self tolerance and white cells to develop specialized functions. the The small bean-shaped structures known as the lymph nodes filter particulate matter and micro-organisms, and produce antibodies to destroy invading organisms and abnormal cells. The defense cells within the lymph nodes are macrophages, which engulf and destroy foreign substances, and lymphocytes, which provide an immune response to antigens (Cann, 2005). The spleen in the upper left section of the abdomen consists of two components which filter blood, destroys worn out blood cells, forms blood cells in the fetus, acts a blood reservoir, and removes abnormal cells from circulation: the red pulp and the white pulp. The red pulp houses a complex system of blood vessels, designed to remove old or damage blood cells from circulation. The white pulp, which contains T cells, B cells and accessory cells, has the role of mounting immunological responses to antigens within the blood. Another important part of the immune system is Gut Associated Lymphoid Tissue, which includes tonsils, adenoids (Waldeyer’s ring), Peyer’s patches, lymphoid aggregates in the appendix and large intestine, lymphoid tissue in the stomach, small lymphoid aggregates in the esophagus, diffusely distributed lymphoid cells and plasma cells in the lamina propria of the gut. The tonsils are small masses of lymphoid tissue in the back of the throat around the pharynx. They act as a filter to trap and remove bacteria and foreign intruders that cause infection. Peyer’s patches in the walls of the small intestine capture and destroy bacteria. They facilitate the generation of an immune response within the mucosal membrane, where B cell precursors and memory cells are stimulated by antigens (Cann, 2005). The Cells of the Immune System and their Function: There are many different types of cells in the immune system that work together to protect the human body. The two main classes of lymphocytes are B cells and T cells, which originate from the hemocytoblasts in the red bone marrow. B lymphocytes mature in the bone marrow, while T lymphocytes mature in the thymus. B lymphocytes play a large role in the humoral immune response and function to produce antibodies in response to foreign proteins such as bacteria, viruses, and tumor cells. Antibodies are specialized proteins that specifically recognize and bind to one particular protein. Antibody production and binding to a foreign substance or antigen is critical as a means of communicating with other cells to engulf, kill or remove that substance from the body. B-cells differentiate to form plasma cells and memory cells. The plasma cells secrete antibodies which help destroy antigens by binding to them and the memory cells produce antibodies to provide immunity to a familiar antigen. There are three different types of T-cells: helper T-cells, suppressor T-cells, and killer T-cells. Helper T-cells (CD4+) activate B-cells that produce antibodies; suppressor T-cells slow down and inhibit Bcells and T-cells from generating an immune response; and cytotoxic (CD8+) aka Killer T-cells recognize and kill virus-infected cells without communicating with other lymphoid organs. Helper T-cells aid the cellular and humoral immune responses by supplying cytokines. Killer T-cells that are activated by CD4+ T-cells secretions kill their viral-infected targets more effectively. B-cells make up 10-20%, helper T-cells make up 68-75%, and killer T-cells make up 5-10% of lymphocytes (Purves, 2001). In addition to B-cells and T-cells, there are monocytes, macrophages, dendritic cells, and granulocytes. These cells are known as phagocytes because they engulf and ingest foreign bodies and harmful micro-organisms while absorbing waste materials in the bloodstream and tissues. Monocytes make up to 1-6% of white blood cells; their function is to circulate in the bloodstream, migrate to other tissues, and differentiate into macrophages. Macrophages, which are phagocytic cells, can be found in a variety of tissues. They play an important role in regulating immune responses because they collect and ingest foreign materials and present the antigens to B-cells and T-cells. Along with activating the immune response, they engulf and digest micro-organisms along with releasing cytokines to activate T-cells. Another type of cells is a dendritic cell, which can be found in the structural components of lymphoid organs i.e. thymus, lymph nodes, and spleen. They capture antigens and transport them to the lymphoid organs, but little is known about these cells due to the difficulty in isolating them (NIAID, 2003). There is another group of white blood cells known as granulocytes or polymorphonuclear leukocytes. There are three cell types that compose granulocytes: neutrophils, eosinophils, and basophils. Their overall role is to remove bacteria and parasites by engulfing these foreign materials and using powerful enzymes to wear them down. Neutrophils, making up 50-70% of white blood cells, respond to inflammation by moving from the blood to the site of inflammation, where they phagocytize debris and pathogens. Another type of cell that makes up 1-3% of white blood cells is an eosinophil. They migrate from the blood to other tissues and kill antibody-coated parasites. Basophils are the third and smallest group of granulocytes that make up less than 1% of white blood cells. Basophils secrete histamine, several proteoglycans, lipid mediators like leukotrienes, and several cytokines, all which contribute to inflammation and an allergic response (Linnemeyer, 1993). Types of Immunity: There are four different types of immunity: natural passive immunity, acquired passive immunity, natural active immunity, and acquired active immunity. Natural passive immunity is where antibodies produced by one individual are passed into another individual i.e. from a mother to her baby. In this type of hereditary immunity, antibodies from a mother cross the placenta and enter her fetus so that they can protect the baby for the first six months of its life, until its own immune system is functional. Passive immunity can also be transferred from a mother’s first milk because the baby’s intestines absorb antibodies. A second type of passive immunity is acquired from vaccines i.e. rabies and tetanus, where antibodies made in one individual are injected into another individual’s blood. It is not permanent and only lasts for a temporary period of time. Just as there are two types of passive immunities, there are two active forms. The first is natural active immunity, in which a person who has suffered a disease and its symptoms becomes immune to it. It is also known as a secondary response, where B-Cells fire off antibodies to combat a recognized antigen. The body makes its own antibodies the first time it is exposed to the infectious agent, and the memory cells that were formed the first time are able to manufacture mass amounts of antibodies when the same antigen presents itself again. An example of this is chicken pox, because after the infectious antigen presents itself once, the body is immune to it, and it generally persists for life. The last type of immunity is acquired active immunity, where a vaccine i.e. polio (small amounts of antigen) is injected in an individual. This small dose guarantees that the individual will not contract that disease and will produce antibodies against the antigen. The Immune Responses: There are two types of immune responses in the human body: cellular (controlled by T-cells) and humoral (regulated by B cells and their antibodies). The cellular or cell-mediated response does not involve antibodies, and instead involves the activation of macrophages and killer T-cells, the production of antigen-specific cytotoxic T-cells, and the release of various cytokines in response to an antigen. In this immune response antigens must be presented to an immunocompetent T- cell by macrophages. The T- cell must recognize if it is non-self or self, an important function of the immune system. After antigen binding, clones form as with B cells, but different classes of cells are produced. The cytotoxic T-cells specialize in killing infected cells by inserting a toxic chemical called perforin. The helper T-cells recruit other cells to fight the invaders and interact directly with B cells. The suppressor T-cells release chemicals to suppress T-cell and B-cell activity, and are like the off switch for the immune response in order to prevent uncontrolled activity (Marieb, 2003). The humoral immune response is regulated by B-cells and the antibodies they produce. Some of the digested antigens are displayed on the surfaces of the macrophages and provide other cells of the immune system with an opportunity to recognize the invader and become activated. In this process known as antigen presentation, the macrophage selects helper T-cells and B-cells which have membrane receptors that are complementary in shape to the antigens exposed. This selection process is known as clonal selection (Millar, 2003). The humoral response pathway diagram (Figure 5) shows that in the humoral immune response, B lymphocytes with specific receptors bind to a specific antigen. This binding activates the lymphocyte to undergo clonal selection, where a large number of clones are produced (primary humoral response). Most B cells become plasma cells, which produce antibodies to destroy antigens, although some B cells become long-lived memory cells (secondary humoral response). The following chart on the next page shows the two types immunities and the process B-cells and T-cells undergo to emit an immune response (Millar, 2003). Disorders: In many cases, the immune system fails. An impaired immune system is called immunocompromise and can leave the body vulnerable to various viral, bacterial, or fungal opportunistic infections. Causes of immune deficiency can include various illnesses such as viruses, chronic illness, or immune system illnesses i.e. AIDS. Other types of immune disorders involve an over-active immune response. There are several different classes of diseases from an excessive response by the immune system: 1. Allergies - a true allergy to a substance or food is caused by the immune response. 2. Asthma - caused by an allergic reaction affecting the airway passages. 3. Anaphylaxis - an extremely dangerous over-reaction that can lead to shock 4. Autoimmune diseases - a group of more than 100 diseases where the body's own immune system gets confused and starts to attack good body cells. In the case of autoimmune diseases like multiple sclerosis, systemic lupus erythematosus, and some forms of arthritis and diabetes, the process of self/non-self recognition breaks down, and the immune system attacks its own cells (Wikipedia Immune System, 2006). Background: Lupus is an autoimmune disease that affects your immune system. Autoimmune diseases are illnesses which occur when the body’s tissues are attacked by its own immune system. It may also be called Systemic Lupus Erythematosus or (SLE). Usually your immune system tries to fight off infections by killing germs, but in Lupus it makes the mistake of attacking its healthy cells instead. Lupus can affect any part of an individual’s body from their joints, kidneys, skin, all the way to their heart and lungs. The body’s immune system normally makes proteins called antibodies to protect the body against viruses, bacteria and other foreign materials. These foreign materials are called antigens. In an autoimmune disorder such as lupus, the immune system loses its ability to tell the difference between foreign substances (antigens) and its own cells and tissues. The immune system then makes antibodies directed against “self.” These antibodies, called “auto-antibodies,” react with the “self” antigens to form immune complexes. The immune complexes build up in the tissues and cause inflammation, injury to tissues, and pain. In some people, Lupus’s effects are not as prevalent as it is in others. A few will only be affected in the joints and skin, but others will be affected in the heart and lungs. Lupus is usually a slow processing disease that has symptoms, which just come and go, but sometimes it becomes life threatening and can become very dangerous about deadly. Lupus can be thought of as a self allergy that attacks its own cells and tissues, which causes inflammation, pain, swelling, and possible organ damage. Patients with lupus produce abnormal antibodies in their blood that target tissues within their own body rather than foreign infectious agents. Lupus can cause disease of the skin, heart, lungs, kidneys, joints, and nervous system. When only the skin is involved, the condition is called systemic lupus erythematosus (SLE). Lupus is one of America’s least recognized diseases but is one of its major diseases. More people in America have lupus than any other disease like anemia, multiple sclerosis, or even cystic fibrosis. It is one of the most prevailing diseases in America, but it is very unnoticeable. However, while lupus is widespread, awareness and accurate knowledge about it lags behind many other illnesses. Statistics: Lupus is on the rise, and scientists don't know exactly why. A recent report from the Centers for Disease Control and Prevention (CDC) revealed a 60 to 70 percent rise in lupus deaths between the years of 1979 and 1998. Each year during the study phase, death rates were more than five times higher for women than for men, and more than three times higher for African Americans than for Caucasians. The LFA market research data show that between 1,400,000 and 2,000,000 people reported to have been diagnosed with lupus. Lupus is more common in women especially in Latino, Asian, and Native American. Women take over 90 percent of the lupus disease population. Lupus is the leading cause of kidney disease, stroke, and premature cardiovascular disease in women of childbearing years. Regrettably, statistics show that 5 percent of children born to lupus-diagnosed mothers will eventually develop the disease themselves. Types: There are several forms of lupus. The first one, which is also the most common type of lupus is Systemic Lupus Erythematosus (SLE). SLE can affect a magnificent amount of parts of the body like joints, skin, kidneys, blood vessels, nervous system, heart, blood, brain, and the lungs. This type of lupus is found in teens and adults from the ages ranging from 15 to 44. Even though SLE happens between these ages it could show early or late symptoms as well. SLE is an elaborate disorder affecting a diminutive young population and shares resemblances with the HIV infection. The etiology of SLE is not known. It can occur at all ages, but is more common in young women. It is also a disease with many manifestations. The immune complex deposition in many tissues leads to the manifestations of the disease. Immune complexes can be deposited in glomeruli, skin, lungs, synovium, mesothelium, and other places. Many SLE patients develop renal complications (Eustice, 2006). Discoid lupus erythematosus (DLE) is a second type of lupus which affects just the skin. Patients with DLE could also get sores in the mouth and throat. Discoid lupus erythematosus is a chronic skin condition characterized by inflammation and scarring type skin lesions which occur on the ears, face, scalp and sometimes on other parts of the body. These lesions develop as a swollen growth with, scaling and a warty like form. The center areas may appear lighter in color encircled by an area darker than the normal skin. When wounds occur in hairy areas such as the scalp, permanent scarring and hair loss can occur. A small percentage of patients with discoid lupus can develop disease of the internal organs which can make the person sick. Not many but a few people with DLE get SLE. It is not known for sure if a DLE person will get SLE. DLE does not affect the organs as SLE does, even though there are a small percentage of people who get DLE have organ failure. The cause of this type is unknown and it is said that this condition tends to run in families; females outnumber males with this condition 3 to 1. In some patients with discoid lupus erythematosus, sunlight may make the lesions come out (Eustice, 2006). The next type of lupus is Neonatal Lupus Erythematosus (NLE). Neonatal lupus occurs in babies. If a woman gets pregnant and she has SLE or any other immune system disorders then the baby could be born with neonatal lupus. Neonatal is a rare type of lupus. In most of the cases neonatal lupus does not need to be treated. In those cases neonatal lupus disappears impulsively in a few weeks, leaving nothing behind. With a simple blood test you will be able to tell which women will deliver a child with neonatal lupus. Many of the children born with neonatal lupus are born to mothers who don’t have SLE. Some of the babies who are born with this disease could have a serious or even sometimes minor heart defect, though most of the time it is serious. Once a baby is born with this heart defect it stays permanent and cannot be cured but treated with a pacemaker (Eustice, 2006). The very last type of lupus is the Drug-Induced Lupus Erythematosus (DILE); it is related to drug prescriptions. This type of lupus is related to a reaction from some sort of prescription medications. This type of lupus will not show right away after you had a reaction to medicine it would have to take months or even years before the first symptoms show and then when you quit taking those medications it would take days, weeks, months, or even years for the symptoms to go away. Lupus-inducing drugs are normally those used to treat chronic diseases. The list includes medicines used to treat: Heart disease, Thyroid disease, Hypertension, Neuropsychiatric disorders, and certain anti-inflammatory agents and antibiotics. At least 38 drugs recently used can cause DILE. However, most cases have been associated with these three drugs: Procainamide (Pronestyl), Hydralazine (Apresoline), Quinidine (Quinaglute). The risk for developing lupus-like disease from any of the other 35 drugs is very low; with some drugs only one or two cases have been reported. For the high-risk drugs such as procainamide and hydralazine, only 5 to 20 percent of people treated for one to two years at currently used doses will develop drug-induced lupus. With most of the other drugs, the risk is less than 1 percent that those taking the medication will develop DILE. Some studies show that Caucasians are more likely to develop this than African Americans. Usually DILE occurs in males over the age of 50, because they have a higher chance of developing chronic diseases that require this type of continuous medication procainamide or quinidine is prescribed for cardiac arrhythmias, and hydralazine is prescribed for hypertension. Obviously men over 50 have both or one of these (Eustice, 2006). Causes: Lupus is a disease whose cause is still unknown, even if it is starting to become one of the major diseases in Americans. It is thought that there is no single cause for any type of lupus but a combination of many things. These include genetic, environmental, and maybe hormonal factors that work together to make this immune disorder come alive. People cannot catch lupus from a person when they sneeze or even when they breath on you because lupus is not contagious, but is known to run in the family. Some of the environmental factors that may trigger the disease are: infections, antibiotics (especially those in the sulfa and penicillin groups), ultraviolet light, extreme stress, and certain drugs (What causes lupus?, 1996). People Affected: Lupus is often called a "woman's disease" despite the fact that many men are affected. Lupus can occur at any age, and in either sex, although it occurs 10 to15 times more frequently among adult females than among adult males. The symptoms of the disease are the same in men and women. People of African, American Indian, and Asian origin are thought to develop the disease more frequently than Caucasian women, but the studies that led to this result are small and need validation. Hormonal factors may explain why lupus occurs more frequently in females than in males. The increase of disease symptoms before menstrual periods and/or during pregnancy support the belief that hormones, particularly estrogen, may be involved. However, the exact hormonal reason for the greater prevalence of lupus in women, and the cyclic increase in symptoms, is unknown. Symptoms: Although lupus can affect any part of the body, most people experience symptoms in only a few organs. Since there is more than one type of lupus each type has its own symptoms. Symptoms Achy joints (arthralgia) Fever over 100 degrees F (38 degrees C) 81% Prolonged or extreme fatigue 90% Arthritis (swollen joints) 74% Skin Rashes 71% Anemia 50% Kidney Involvement 45% Pain in the chest on deep breathing (pleurisy) 42% Butterfly-shaped rash across the cheeks and nose 27% Hair loss 17% Raynaud's phenomenon (fingers turning white and/or blue in the cold) 15% Seizures 12% Mouth or nose ulcers SLE type can present itself in very different ways regarding of the person’s body. About 80% of people develop joint and muscle pain, skin rashes, fatigue and a general feeling of being unwell. Often symptoms are worse before a menstrual period and they are often thought to be just pre-menstrual tension. The most common signs and symptoms are arthritis, fatigue, skin rashes, sun sensitivity, hair loss, kidneys, Percentage 95% 90% depression, and some other symptoms. During a lupus flare-up the most common complaints are of flu-like symptoms (with or without fever), fatigue, muscle and joint pains. Often symptoms are reported to be worse before a menstrual period and they are often thought to be just pre-menstrual tension. People with lupus can also have a variety of other symptoms including high temperature, blood disorders, miscarriage, headaches, weight loss, chest pain and abdominal pain. However, it is important to remember that the symptoms can vary greatly from person to person. People with DLE tend to be quite sensitive to the sun. They are more likely to get sunburn and the sun is likely to worsen their discoid lesions (Lahita, 2001). Neonatal Lupus has few symptoms like skin rash, liver abnormalities, low blood counts, and heart defects. Since it happens in babies given by the mom who is pregnant with the baby the symptoms could be seen in the mom. Flares most often occur during the first or second trimester, or during the two months immediately after delivery. Most of the flares tend to be mild. Approximately 33 percent of lupus patients will have a decrease in platelet count during pregnancy, and about 20 percent will have an increase in or new occurrence of protein in the urine. It is important to distinguish the symptoms of a lupus flare from the normal body changes that occur during pregnancy (Lockshin, 1994). Treatments: Treatments for lupus are not easy to find. There is no known cure for lupus so the only option is to use home care. Home care for lupus generally involves taking prescribed medications and using sunscreen whenever patients go outside because lupus patients are known to be sensitive to the sun. For most of the symptoms, they can take medications because the symptoms are from swelling or inflammation and there are medications for it. Some medications are non-steroidal anti-inflammatory drugs (NSAIDS), which are often used to moderate joint/muscle pain and inflammation in people who have minor SLE. This medication comes in many different forms. Another kind of medicine is anti-malarial drugs, which are medicines that are used to prevent or treat malaria, joint pain, skin rashes, and ulcers. Two types of anti-malarials are hydroxychloroquine (Plaquenil) and chloroquine (Aralen). In addition, there are corticosteroid hormones that are powerful drugs, which reduce inflammation in various tissues of the body. This medication can be taken by mouth, by cream applied to the skin, or by injection. When a patient has a severe case of lupus and their major organs don’t function properly, there is a treatment that is used known as Immunosuppressive agents/chemotherapy. All of these drugs suppress the immune system to limit damage to the organs. Some examples are azathioprine (Imuran) and cyclophosphamide (Cytoxan). For a patient without a known diagnosis of lupus, the doctor will assess, but never likely provide a major diagnosis of lupus unless there are clear and unmistakable features. Evaluation of chronic (not acute) diseases is done in a medical office setting. However, certain tests to assess the possibility of organ damage including some blood and urine tests, imaging studies, and heart tracings will allow the doctors to assess an acute disease if someone with lupus seeks treatment in an emergency department (Lahita, 2001). Works Cited (1996). What causes lupus?. Retrieved July 13, 2006, from MedicineNet Web site: http://arthritis.about.com/od/lupus/a/guidetolupus.htm (1998). MayoClinic. Retrieved July 13, 2006, from Lupus Web site: http://www.mayoclinic.com/health/lupus/DS00115/DSECTION=2 B cells. (2006). In Wikipedia [Web]. Retrieved 10 July, 2006, from http://en.wikipedia.org/wiki/B_cells Cann, Alan (2005, Nov 11). The Anatomy of the Immune System. 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