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Home , Leukemia

CH 14 LECTURE OUTLINE I. Introduction A. The immune and lymphatic systems protect the body from - that can produce disease B. Methods of protection 1. If pathogens try to enter the body, they must first get past the barriers, such as intact skin and the secretions of mucous membranes 2. If the does get into the body, the body recognizes it as not belonging in the body a. This stimulates a series of responses to neutralize the pathogen b. Weapons include special cells and powerful chemicals of the immune and lymph systems c. Other chemicals stimulate inflammatory and clean-up responses C. The combined efforts of the lymphatic and immune systems are required to accomplish this protection II. The A. The lymphatic system is both the transport system and “barracks” of the immune system B. It works closely with the cardiovascular system C. The lymphatic system has four functions 1. Recycling fluids lost from the cardiovascular system 2. Transporting pathogens to the lymph nodes where they can be destroyed 3. Storage and maturation of some types of white cells 4. Absorption of glycerol and fatty acids from food D. Structures of the lymphatic system (lymph vessels and lymph organs) 1. Lymph capillaries a. Tiny open-ended “pipes” that form a network between cells of connective tissues b. These pipes, which are the smallest in the lymphatic -system, move a fluid called lymph (lymphatic fluid) 2. Lymph capillaries empty into lymphatic vessels, which are similar to veins and have valves a. Body movement and contraction of smooth muscles propel the lymph 3. Large lymphatic vessels empty into lymph nodes a. Many lymph vessels empty into each node b. Lymph nodes are small, encapsulated bodies that can range from the size of a pinhead to the size of an olive i. They act like “filters” for the lymph ii. Inside, the node is divided into sections called -lymphatic sinuses • Each sinus contains white cells (WBCs) known as • These WBCs destroy pathogens in the lymph c. Lymph nodes are concentrated in the cervical, axillary, inguinal, pelvic, abdominal, thoracic, and supratrochlear areas i. Adenoids and , the , and the thymus also contain lymph tissue 4. Lymphatic vessels exiting lymph nodes empty into one of -several lymphatic trunks a. Lymph trunks are named for their location and include the lumbar, intestinal, intercostal, bronchomediastinal, -subclavian, and jugular trunks b. Lymph trunks empty into one of two collecting ducts: i. Thoracic duct • A large duct that runs from the abdomen up through the diaphragm • Empties into the left subclavian vein • Receives lymph from more than two-thirds of the lymphatic system, including - Lumbar trunk - Intestinal trunk - Intercostal trunk ii. Right lymphatic duct • A smaller duct within the right thorax • Empties into the right subclavian vein • Receives lymph from: - Bronchomediastinal trunk - Subclavian trunk - Jugular trunk 5. The lymph ducts empty into the subclavian veins (as noted earlier) a. The thoracic duct empties into the left subclavian vein b. The right lymphatic duct empties into the right subclavian vein 6. The circulation of fluid then follows this pattern, beginning and ending in the bloodstream a. Fluid leaks out of the bloodstream into the tissue b. Tissue fluid goes into lymphatic capillaries c. Lymphatic capillaries carry fluid (lymph) to lymphatic vessels d. Lymphatic vessels carry fluid to lymph nodes e. Lymph nodes filter fluid to remove pathogens; i. Then fluid is delivered to other lymphatic vessels f. Lymphatic vessels carry fluid to lymph trunks g. Lymphatic trunks carry fluid to collecting ducts h. Collecting ducts carry fluid to the subclavian veins, where it reenters the bloodstream 7. Pathology Connection: Tonsillitis a. Tonsillitis i. An inflammation of the tonsils, usually caused by -bacterial or viral ii. Symptoms • Sore throat • Swollen tonsils • • Upper respiratory symptoms • Swollen lymph glands • Visible coating or spots on the tonsils • Sometimes upset stomach iii. Diagnosis • Based on the presence of visible inflammation on physical exam • Throat culture can distinguish between bacterial and viral causes of tonsillitis iv. Treatment • Bacterial tonsillitis must be treated with antibiotics • Viral tonsillitis will resolve on its own • In both types of tonsillitis, symptoms are managed with rest, fluids, and analgesics like Tylenol • Tonsillectomy - Used regularly as a treatment in the past - Today only used if tonsillitis becomes chronic, or if tonsils become enlarged to the point of obstructing the airway 8. Lymph organs—collections of lymphatic tissue (similar to that seen in lymph nodes) located outside the lymph circulation a. Tonsils i. Structures in the throat that contain lymphatic tissue ii. The three sets of tonsils are • Palatine tonsils (located on either side of the orthopharnyx) • Pharyngeal tonsils (known as the adenoids that are located at the posterior of the nasopharynx) • Lingual tonsils (located at the base of the tongue) b. Spleen i. A spongy organ in the upper-left quadrant of the abdomen ii. Structurally similar to lymph nodes but instead of lymphatic sinuses, has blood sinuses • Blood sinuses surround islands of white pulp -containing lymphocytes and islands of red pulp containing both red blood cells (RBCs) and WBCs iii. Functions of the spleen • Removes and destroys old, damaged, or fragile RBCs • Filters pathogens from bloodstream and destroys them iv. Not an essential organ and can be surgically removed if necessary (due to trauma, etc.) • Removal in children can severely compromise immunity but has far less effect on adults v. Because of its rich blood supply, injury to the spleen can cause internal c. Thymus i. Soft organ located between the aortic arch and sternum ii. Very large in children because of all the new - it must handle iii. Gets smaller, but continues to have some activity in adults as the immune system fully matures in its -ability to fight infection iv. Packed with lymphocytes, which mature into a type of WBC called a T- v. Also secretes a hormone (allowing it to also be referred to as an endocrine gland) that stimulates maturation of the T lymphocytes in lymph nodes 9. Pathology Connection: Lymphatic Disorders a. Lymphadenitis i. Disorder of the lymphatic system in which lymph nodes swell • Can affect a small area (localized) or a large area (generalized) • Often caused by a bacterial infection, but may also be the result of , parasites, and fungi ii. Symptoms • Swelling of lymph nodes (initial symptom) • Increased production of white blood cells (initial symptom) • Fever, chills, excessive sweating, rapid pulse, and weakness are more advanced symptoms iii. Treatment • May be treated with infection-specific (antibacterial or antiviral medication) • Rest of affected area • Hot moist compresses b. Mononucleosis (“kissing disease”) i. Caused by the Epstein-Barr that typically affects children and young adults • Can be spread through oral contact or exchange of saliva • Effects may continue from two weeks to two months after infection ii. Symptoms • • Sore throat • Fever • Lymphadenitis • Increase number of lymphocytes iii. Treatment • No specific treatment • Patient is told to get plenty of bed rest • Antibiotics may be prescribed to treat secondary infections c. Hodgkin’s disease (Hodgkin’s ) i. Rare of the lymphatic system • Characterized by and itchy skin • Unknown cause, but being a young or older adult, the Epstein- Barr infection, and being a male can contribute to the likelihood of developing the disease ii. Symptoms • Swollen lymph nodes, unexplained , , and fatigue are early symptoms iii. Treatment • May be treated successfully if caught early with , radiation, or a combination of both 10. Pathology Connection: Cancer Stages and the Lymphatic System a. i. Cancer cells can spread around the body via the -lymphatic system • The degree of spreading can be used to predict a patient’s - that have already spread at the time of diagnosis are much more likely to be fatal - The earlier a patient with cancer is diagnosed, the better their chances of beating the disease ii. Stages of cancer (based on degree of spread) • Stage 1—no spread from origin • Stage 2—spread to local tissues • Stage 3—spread to lymph nodes • Stage 4—spread to distant organs (often terminal) III. The Immune System A. The lymphatic system and immune system work together to defend the body against invaders 1. As previously discussed, the lymphatic system is considered the transport system and “barracks” of the body’s defense 2. The immune system provides the weapons and the troops that protect the body from a. It consists of cells, chemicals, and barriers that protect against pathogens b. Some processes are active, some passive, some inborn, and others change with experience B. and antibodies 1. In order to function, the immune system must be able to -identify which cells are invaders and neutralize them a. Antigens i. Molecules on the outer surface of the cells that -identify them as friend or foe • Each living thing has unique cell surface antigens, allowing the immune system to identify invaders ii. Self- and non-self-recognition are at the heart of how the immune system functions • A well-functioning immune system ignores -self-antigens and attacks non-self-antigens b. Antibodies i. Proteins produced by the body that bind to foreign antigens, eventually destroying them ii. Antibodies are called into action when a foreign - invades the body C. Innate versus adaptive immunity 1. Innate immunity a. Is the body’s inborn ability (a part of our that is not affected by our environment) to fight infection b. Is the front line of defense against invasion i. Prevents invasion, or if the invasion occurs, it takes steps to prevent the spread of infection c. Can recognize invaders as being foreign, but cannot identify them specifically i. Therefore, it cannot “remember” a previous invader or improve with experience d. Innate immunity is a collection of crude, general mechanisms i. Some kill healthy tissue as well as pathogens and healthy tissue alike 2. Adaptive immunity (or acquired immunity) a. Targets specific invaders b. Spares healthy tissue as much as possible c. Remembers invaders from previous encounters i. Allows body to prepare for future invasion, and improves the protective responses with experience by learning and changing 3. Innate and adaptive immunity are not two separate entities but work together: a. Innate immunity prepares the way for adaptive immunity, weakening some pathogens and stimulating components of adaptive immunity b. Adaptive immunity, in turn, stimulates innate immunity D. Components of the immune system 1. The immune system has numerous defensive components: a. Barriers—which prevent pathogens from invading b. Cells—which help fight off pathogens that make it past the barriers c. Chemicals—which help neutralize and destroy invaders 2. Barriers a. Act as first-line defense by preventing invaders from -getting inside the body b. Located in areas most likely to be invaded: i. Skin ii. Mucous membranes (of the eyes, digestive, respiratory, and reproductive systems) c. These surfaces are difficult to penetrate and are packed with WBCs and lymph capillaries to trap invaders d. Fluids associated with physical barriers may also contain chemicals that act as barriers i. Examples: • Tears • Saliva • Urine • Mucous secretions • Sweat • Oil from the sebaceous glands e. Barriers are part of innate immunity 3. Cells a. Are a second line of defense against pathogens that manage to get by barriers b. Leukocytes (also called white blood cells or WBCs) are the cells that defend the body against invaders c. WBCs originate in the marrow and often move to other parts of the body to grow and mature until they are needed during an invasion d. WBCs are generally not released into the bloodstream until they are needed e. Types of WBCs: i. • Function—Perform phagocytosis early in infection • Part of innate immunity ii. and mast cells • Basophils are mobile cells • Mast cells are found in connective tissue and are not mobile • Function of both basophils and mast cells: - Release chemicals to promote inflammation • Both are part of innate immunity iii. • Function—Counteract the actions of basophils • Are part of innate immunity iv. Macrophages • Functions - Perform phagocytosis later in infection - Helps further stimulate the immune system by displaying foreign antigens • Part of innate immunity, but helps stimulate -adaptive immunity v. Dendritic cells • Functions: - Weakly phagocytic - Helps further stimulate the immune system by displaying foreign antigens • Part of innate immunity, but helps stimulate -adaptive immunity vi. Natural killer cells • Function—release chemicals to kill any cells -displaying foreign antigens—pathogenic or your own cells • Part of innate immunity vii. T-lymphocytes (T cells) • Functions: - Kill infected cells - Activate and regulate immune response - Remember past infections • Part of adaptive immunity viii. B-lymphocytes (B cells) • Functions: - Release antibodies that fight foreign antigens - Remember past infections • Part of adaptive immunity 4. Chemicals a. Cytokines i. Proteins produced by damaged tissues and WBCs ii. Stimulate immune response by • Increasing inflammation • Stimulating lymphocytes • Enhancing phagocytosis iii. Involved in both innate and adaptive immunity iv. Types of cytokines: • Interferons - Cytokines produced by cells that have been infected by a virus - Function: a. Binds to neighboring, uninfected cells and stimulates them to produce chemicals that may protect these cells from viruses - Has also had some success as an anticancer drug, but are still experimental • Tumor necrosis factor (TNF) - Another cytokine - Functions: a. Stimulates macrophages b. Causes cell death in cancer cells • Interleukins - There are at least 10 different kinds of interleukins - Interleukins are involved in nearly every aspect of innate and adaptive immunity - Interleukins have been used with moderate -success to treat some forms of cancer b. Complement cascade i. A complex series of reactions that activate a series of plasma proteins in the blood • These proteins are usually inactive • They are activated by a pathogen invasion ii. When activated, these proteins have a variety of effects, including • Lysis of bacterial cell membranes • Stimulation of phagocytosis • Attraction of WBCs to site of infection iii. Complement cascade is part of both innate and -adaptive immunity E. Pathology Connection: 1. A cancer of the and blood 2. Characterized by the overproduction of white blood cells a. In some forms of leukemia, these cells are immature or nonfunctional 3. Types of leukemia a. myelogenous leukemia b. Chronic myelogenous leukemia c. Acute lymphocytic leukemia d. Chronic lymphocytic leukemia 4. Myelogenous a. The cells that divide out of control are blood stem cells 5. Lymphocytic leukemia a. The cells that divide out of control are lymphocytes 6. Acute leukemias a. Have rapid onset of symptoms b. Overproduced WBCs are immature, nonfunctional cells 7. Chronic leukemias a. Have gradual onset b. Overproduced WBCs are mature, functional cells 8. Epidemiology a. Some types of leukemia are more common in children; -others are more common in adults b. Chronic myelogenous leukemia is associated with the - (a chromosomal abnormality) c. patients are at higher risk for acute -myelogenous leukemia 9. Symptoms a. Symptoms that develop are caused by i. Decreased function of immature WBCs (in types of leukemia with immature cells) ii. Decreased numbers of red blood cells and (which are crowded out by the excessive numbers of WBCs) b. Possible symptoms: i. ii. iii. Fatigue iv. Repeated infections v. Enlarged lymph nodes vi. Weight loss vii. Muscle aches viii. Excessive bruising ix. Bleeding c. Diagnosis i. ii. Bone marrow iii. Sometimes genetic testing is also used d. Treatment may include i. Chemotherapy ii. Antibody treatments iii. Bone marrow transplant e. Prognosis varies with the type of leukemia i. Chronic lymphocytic leukemia has no cure, but -symptoms can be managed for years ii. Acute lymphocytic leukemia is common in childhood and has a very high rate of successful treatment F. Inflammation 1. Reaction is a deliberate action of the body in response to tissue damage, whether a mechanical or pathological injury a. Response helps to wall off the damaged area to prevent -further spread and allow the battle to focus at this site—called margination 2. Cardinal symptoms of inflammation include pain, swelling, heat, and redness 3. Steps in the inflammatory response: a. When tissue is damaged, cells release chemicals such as like histamine, an inflammatory modulator b. These chemicals: i. Attract WBCs to the site ii. Increase the permeability of capillaries iii. Cause local vasodilation c. More blood comes to the site, causing heat d. Extra fluid leaking out of the capillaries causes swelling e. WBCs destroy pathogens and clean away dead cells f. The increased fluid and cells in the area increases pressure and contributes to pain felt in the area 4. Inflammation is an innate immune mechanism but plays an important part in adaptive immunity G. Pathology Connection: Inflammation, a Two-Edged Sword 1. Inflammation has a positive feedback loop; once it starts, it will continue until it is “turned off” a. Too much inflammation, particularly in closed spaces (like the brain, spinal cord, or respiratory system), can cause more tissue damage than the original injury or infection 2. Inflammation can be treated with several , including a. Nonsteroidal anti-inflammatory drugs (NSAIDS) -including ibuprofen and naproxen b. Steroids c. Antihistamines (especially for allergic reactions) 3. Widespread (systemic) inflammation is called anaphylaxis a. Causes widespread vasodilation and blood pressure plummets b. Can be fatal if not treated by a medical professional immediately i. Many patients prone to anaphylaxis carry injectable epinephrine (adrenalin) to treat acute reactions c. People who are allergic to insect stings, nuts, or shellfish may experience anaphylaxis H. Fever 1. During an infection, the immune system releases cytokines that promote inflammation and immune response 2. These cytokines travel through the bloodstream and -eventually reach the hypothalamus (in the brain) a. The hypothalamus is responsible for setting and maintaining body temperature b. Under the influence of cytokines, the hypothalamus raises the body’s temperature setpoint i. You suddenly feel cold and attempt to warm up by dressing more warmly or covering up with blankets ii. You may begin to shiver c. Body temperature becomes elevated, resulting in a fever 3. This rise in body temperature is a deliberate attempt by immune system to destroy pathogens 4. Fever is part of the innate immune response IV. How the Immune System Works A. Innate immunity 1. Activation of the innate immune response a. First, the pathogen must get past physical and chemical barriers; most pathogens are kept out by these barriers b. The presence of a foreign antigen is detected by neutrophils, which ingest the foreign antigen, destroying it and releasing chemicals that attract other WBCs to the site of infection, stimulating inflammation c. The release of cytokines and stimulation of inflammation attract macrophages and natural killer cells to the infection site d. Macrophages phagocytize infected cells and NK cells use chemicals to destroy infected cells; both cells release chemicals to further stimulate inflammation, activate more immune cells, and trigger the complement cascade e. Chemicals signal the hypothalamus to raise body temperature 2. Pathogens are now under attack from phagocytosis, noxious chemicals, membrane rupture, clumping, and even alteration to molecular structure 3. This is crude warfare that destroys anything non-self; -sometimes healthy cells are killed too 4. In some cases, the innate immune response is enough, but often innate immunity is buying time for adaptive immunity a. Innate immunity stimulates adaptive immunity b. When phagocytic cells ingest pathogens, they display the foreign antigen on their cell membrane, essential to -activate B and T cells B. Pathology Connection: Autoimmune Disorders 1. Autoimmune disorders occur when the immune system attacks some part of the body a. The body fails to recognize self and destroys its own tissues 2. There are hundreds of different disorders, each affecting a -different system 3. Examples of autoimmune disorders (and the tissues they attack) a. Rheumatoid arthritis (joint linings) b. Multiple sclerosis (myelin sheath in CNS) c. Lupus erythematosus (every tissue, perhaps DNA) d. Type 1 diabetes (beta cells in pancreas) e. Myasthenia gravis (acetylcholine receptors in skeletal muscle) f. Graves’ disease (thyroid gland) g. Addison’s disease (adrenal gland) 4. Treatment is frequently with immunosuppressant drugs, but they may not be successful, and side effects can be severe 5. Rheumatoid arthritis a. An autoimmune disorder where the synovial membranes of the joints are attacked i. Leads to • Destruction of bone and cartilage in the joints • Weakening of soft tissue supporting the joints ii. Eventually, this can result in • Joint collapse • Fusion of • Shortening of tendons • Disfigurement (particularly of the hands and feet) iii. Symptoms • Joint stiffness • Symmetrical joint damage • Fatigue • Fever • Systemic symptoms may include - Anemia - Dry eye - - Lung, pericardial, and blood vessel inflammation - Increased risk of heart attack • Most patients have a relapsing-remitting pattern of symptoms iv. Epidemiology • There are juvenile and adult forms of the disease • Women are two to three times more likely than men to have RA v. Cause appears to be a combination of genetics and some environmental trigger (such as a virus, bacteria, or hormonal changes) vi. Diagnosis • There is no definitive test for RA • Diagnosis typically consists of - Medical history - Physical exam - Imaging - Lab tests a. Leukocyte counts b. Erythrocyte sedimentation rate c. Test for presence of vii. Treatment • Drugs - DMARDs (disease-modifying antirheumatic drugs) a. Injected gold b. (a cancer drug) c. Plaquinil (a malaria drug) - Biological Response Modifiers (BRMs)—-suppress the immune system by decreasing immune enhancing chemicals • Lifestyle changes - Stress reduction - Moderate exercise - Healthy eating • Assistive devices or surgery are often necessary in severe cases of RA 6. Systemic lupus erythematosis (SLE) a. A disorder in which the immune system attacks connective tissue (which is found in nearly every part of the body) b. Symptoms may include i. Fatigue ii. Joint pain and stiffness iii. Fever iv. Rashes (particularly butterfly-shaped rashes on the face) v. Kidney disease vi. Chest pain vii. Hair loss viii. Swollen glands ix. Anemia x. Heart problems xi. Atherosclerosis xii. Depression or anxiety c. Course of disease may be chronic or show a relapsing-remitting pattern d. Cause of disease is unknown, but both genetics and an environmental trigger is probably necessary for the onset of disease e. Diagnosis i. Difficult, because symptoms vary so much from patient to patient, and there is no definitive test ii. Diagnosis typically includes • Medical history • Imaging studies • Tissue • Lab tests - Blood counts - Urinalysis - Erythrocyte sedimentation rate - Complement levels - Testing for antinuclear antibodies iii. Treatment • Drug treatments - NSAIDs - DMARDs - Steroids - Immunosuppressants • BRM drugs are also being investigated for this disease C. Adaptive immunity 1. Adaptive immunity fights pathogens specifically 2. This part of the system has memory, learns from experience, and recognizes specific pathogens through a. Lymphocyte selection b. Lymphocyte activation c. Lymphocyte proliferation 3. Lymphocyte selection a. To function correctly, lymphocytes must be able to -recognize the difference between pathogens and the body’s own tissues b. The processes of positive and negative selection assure that only correctly functioning lymphocytes survive c. Positive selection i. T lymphocytes that recognize self-antigens are allowed to survive ii. T lymphocytes that do not recognize self-antigens are neglected and die d. Negative selection i. Destroys or deactivates T lymphocytes that will destroy self- antigens e. Both positive and negative selection must work for the immune system to function properly 4. Lymphocyte activation a. Lymphocytes develop, mature, and are selected when you are young i. During the maturation process, they become -differentiated, growing to be specialized cells with a special function ii. Undifferentiated lymphocytes are produced in the bone marrow • Some migrate to the thymus and become T cells when they are mature • Others develop and mature in the bone marrow to become B cells iii. Lymphocytes, once specialized, wait in the for a pathogen they recognize iv. They can remain in suspended animation for a long time b. These lymphocytes must then be “activated” to battle pathogens i. Process of lymphocyte activation: • Cells of the innate immune system (macrophages, dendritic cells, and others) phagocytize pathogens • After phagocytosis, the pathogen’s antigens are -displayed on the outside of the cell • These antigen-displaying cells then prowl the lymph nodes in search of lymphocytes that recognize the antigen • When the right match is found, the matching -lymphocytes are activated • This is the beginning of adaptive immunity 5. Lymphocyte proliferation a. Activated lymphocytes must make thousands of copies of themselves to effectively fight off the reproducing pathogens i. This process is called lymphocyte proliferation b. The process of proliferation varies depending on the type of lymphocyte i. Effector T cells (comprised of helper T cells and -cytotoxic T cells) • Are stimulated to divide by - Binding to antigen-displaying cells (like -macrophages and dendritic cells) - Cytokines secreted by the cells of the innate immune response • Helper T cells then go on to activate and -stimulate the proliferation of other lymphocytes (except cytotoxic T cells) ii. B cells and several other types of T cells • Are activated and stimulated to proliferate by helper T cells 6. B and action a. B cells i. B cells are responsible for antibody-mediated immunity • They fight pathogens by making and releasing -antibodies to attack a specific pathogen ii. Proliferating B cells develop into plasma cells and memory B cells • Each of these cells contributes to antibody mediated immunity • Plasma cells make antibodies and release them into the bloodstream - Antibodies bind to antigens of infected cells - This destroys the pathogen by a. Inactivating the antigen b. Causing clumping of antigens c. Activating complement cascade d. Releasing chemicals to stimulate the immune system and enhance phagocytosis - This process is called the primary response • Memory B cells are stored in lymph nodes in case of future infection with the same pathogen - If reexposed to this same pathogen, the memory B cells allow a much faster and stronger response than seen in the previous infection - This process is called the secondary response a. It is responsible for the immune system’s -ability to improve with experience b. T cells i. After activation and stimulation by helper T cells, the other T cells proliferate ii. Types of T cells: • Helper T cells and cytotoxic T cells (collectively known as effector T cells) • Regulatory T cells • Memory T cells iii. Cytotoxic T cells • Responsible for cell-mediated immunity • Directly kill pathogens or pathogen-infected cells - Release a cytokine called perforin, which causes infected cells to develop holes in their -membranes and die • Also release other cytokines that stimulate innate and adaptive immunity, especially attracting -macrophages to the site of infection to dispose of cellular debris • This process is called the primary response iv. Regulatory T cells • The off-switch for the immune system • Regulatory T cells (along with eosinophils from the innate immune system) turn off the immune response when the threat is over - This is important so that the immune response does not get out of control and cause unnecessary tissue damage • Though regulatory T cells are not fully understood, evidence suggests they - Directly inhibit B cells and cytotoxic T cells - Release cytokines that decrease immune and inflammatory response v. Memory T cells • Store the recognition of the pathogen in case of future encounters with it • This process is called the secondary response D. Pathology Connection: HIV and AIDS 1. Acquired immune deficiency syndrome (AIDS) is an immune deficiency disorder caused by infection with the human - virus (HIV) 2. AIDS is characterized by severely decreased immune function; this happens because the HIV virus a. Directly kills helper T cells b. Destroys lymph nodes due to chronic infection c. Decreases the amount of immune enhancing chemicals in the body 3. HIV is contracted through exposure to infected body fluids. This can occur during a. Sexual contact b. IV drug use c. Consumption of breast milk from infected mothers d. Development of fetuses in HIV-infected mothers e. Accidental exposure to infected body fluids (this is rare) f. Blood transfusions, if the donor was HIV infected (this is also rare in the U.S. today because of intense screening procedures) 4. Symptoms of HIV and AIDS a. Approximately 4 weeks after HIV infection, patients will develop flulike symptoms i. This occurs as the body makes its first attempts to fight off the virus b. The immune system may continue to fight off the disease for the next 10-12 years without having any obvious symptoms c. Eventually, the disease progresses to full-blown AIDS. At this time symptoms may include i. Opportunistic infections ii. CNS dysfunction iii. Some forms of cancer 5. Diagnosis a. Medical history b. Low helper T cell count (of less than 200 cells/uL3) 6. Treatment a. Patients with HIV usually receive a combination of antiviral drugs that i. Block viral reproduction ii. Keep the virus from assembling new viruses iii. Block the entrance of virus into cells b. These drug regimens are complicated and have severe side effects c. However, these drugs are effective at postponing the -development of full-blown AIDS E. Acquiring immunity 1. The adaptive immune system is able to create memory cells each time you meet a new pathogen a. This process is called immunization (whether natural or done by vaccination) b. Because of these memory cells, the next time you are exposed to the pathogen, it is fought off very rapidly, and you do not get ill 2. There are two basic ways of acquiring immunity: a. Active immunity—antibodies are actively produced by your body b. Passive immunity—antibodies are introduced into your body from an outside source (your body does not make its own antibodies) 3. These types of immunity may be naturally or artificially acquired a. Natural active immunity—creation of memory cells resulting from actual infection b. Artificial active immunity—creation of memory cells resulting from vaccination (deliberate exposure to -weakened pathogen) c. Natural passive immunity—immunity (in the form of -antibodies) transferred across the placenta during fetal development or transferred from mother to baby during breast feeding i. This process is important, because newborn babies cannot make their own antibodies yet d. Artificial passive immunity—when a patient is injected with antibodies that were produced by another person V. The Big Picture A. If an army of pathogens wants to invade your body, first, they must get past the body’s barriers B. If they enter the body 1. Immune cells (neutrophils, macrophages, basophils, etc.) are stimulated 2. Chemicals (cytokines) are released that stimulate inflammation and phagocytosis C. Macrophages and other cells that have ingested some of the invaders 1. Display the foreign antigens 2. Move to the lymphatic system, and search the lymph nodes for T and B cells that will recognize the intruder D. Helper T cells are activated and cause 1. The proliferation of B cells and other T cells 2. The release of chemicals to further stimulate phagocytosis and inflammation E. Cytotoxic T cells are activated and proliferate 1. Cytotoxic T cells: a. Destroy invaders directly b. Release chemicals that further stimulate immune response F. B cells produce antibodies that destroy the invaders and further stimulate immune response G. This entire immune response will continue to be stimulated until the feedback loop is stopped, at least in part by regulatory T cells H. Memory B cells and T cells are stored in lymph nodes for later use if another army of these same types of pathogens invade I. Macrophages and other phagocytic cells will clean up the debris left by the warfare, and the body will return to normal J. Pathology Connection: Hypersensitivity Reactions 1. Hypersensitivity reactions, or allergies, occur when the immune system mounts an overactive response to a foreign antigen, often treating a harmless antigen like an invading pathogen 2. Local hypersensitivity reactions, such as hay fever, hives, or rashes, are generally mild and not life threatening a. A local response begins when mast cells in a body part are stimulated by an allergen b. Other immune cells also get involved, including basophils, B cells, eosinophils, and macrophages c. The activation of these cells leads to increased inflammation and release of immune stimulating chemicals d. Symptoms will develop in whatever area the mast cells are stimulated i. Stimulation in the eyes—causes red, runny eyes ii. Stimulation in the nose—causes runny nose (allergic rhinitis) iii. Stimulation in the lungs—causes allergic asthma e. Many patients with one type of allergy also suffer from other allergies i. Example—a patient with hay fever may also suffer from allergic asthma f. Some patients experience progressive worsening of their allergy i. The first exposure may cause only a rash ii. Subsequent exposures may cause more serious -reactions such as asthma or even anaphylaxis 3. Systemic hypersensitivity reactions, or anaphylaxis, are life threatening a. Mast cells and basophils release immune-stimulating -chemicals throughout the body, causing widespread vasodilation b. This leads to dangerously low blood pressure and heart failure 4. Diagnosing allergies is difficult a. may show increased immune activity, but may not pinpoint the allergen b. Exposing the patient’s skin or blood sample to suspected allergens may help find the allergen, but these tests are often inconclusive 5. Treatment a. The best treatment is avoidance of the allergen i. If the patient is allergic to a common substance like grass, mold, or pollen, this might not be possible b. Medications can be used if the allergen is unavoidable VI. Pharmacology Corner A. Anti-inflammatory drugs—decrease inflammation 1. Nonsteroidal anti-inflammatory drugs (NSAIDs) a. Examples—aspirin, naproxin, ibuprofen, Celebrex b. Relieve pain and inflammation by inhibiting hormones called prostaglandins c. Side effects can include formation of stomach ulcers 2. Steroids a. Examples—, cortisone b. Can be administered i. Systemically (orally or by injection) • Systemic steroids can have dangerous side effects if used for long periods of time ii. Topically (applied to skin, nasal passages, or inhaled) • Topical steroids do not have severe side effects due to low dosages • Common uses include • Skin inflammation • Upper respiratory symptoms due to allergies • Asthma symptoms B. Drugs for allergies 1. Antihistamines—decrease mast cell activation a. Very effective, but older antihistamines may cause severe drowsiness 2. Drugs that block cytokines 3. Drugs that block the antibodies that mediate allergies 4. Topical steroids (inhalers or nasal sprays) 5. Epinephrine self-injections (EpiPens) are carried by people prone to anaphylaxis a. In an anaphylactic emergency, the shot of epinephrine constricts blood vessels and opens air passages, allowing time to seek medical attention C. Drugs for autoimmune disorders 1. Disease modifying anti-rheumatic drugs (DMARDs) a. Mechanism of action is not well understood b. Can be toxic c. Examples: i. Immunosuppressants (like cyclosporine, an -antirejection drug for transplant patients) ii. Gold shots iii. Methotrexate (a chemotherapy drug) iv. Anti-malarial medications 2. Biological response modifiers (BRMs) a. Given to patients who have used DMARDs unsuccessfully b. Suppress the immune system by decreasing immune enhancing chemicals or inhibiting the proliferation of cells c. Examples: i. Drugs that inhibit Tumor Necrosis Factor (TNF—a cytokine) • Etanercept (Enbrel®) • Infliximab (Remicaide®) • Adalimumab (Humira®) ii. Anakinra (Kineret®)—inhibits interleukin-1 iii. (Rituxan®)—inhibits B cells d. Side effects may include i. Increased risk of infection ii. Increased risk of some forms of cancer e. However, BRMs are less toxic than DMARDs and do a better job at decreasing fatigue in RA patients VII. A Quick Trip Through Some Diseases of the Immune System A. Lymphoma 1. Etiology—Uncontrolled proliferation of lymphocytes (30 different types) 2. —Enlarged lymph nodes, fever, weight loss, other vague symptoms 3. Diagnostic tests—Biopsy, imaging, bone marrow tests 4. Treatment—Chemotherapy, radiation, antibody therapy, stem cell or bone marrow transplant B. Tonsillitis 1. Etiology—Inflammation of the tonsils due to bacterial or viral infection 2. Signs and symptoms—Sore throat, swollen tonsils, fever, upper respiratory symptoms, swollen lymph nodes, visible coating or spots on the tonsils, upset stomach 3. Diagnostic tests—Examination showing inflamed tonsils, rule out bacterial infection 4. Treatment—If bacterial, treat with antibiotics. If viral, rest and fluids until virus runs its course. If swollen tonsils impair breathing, tonsillectomy may be necessary C. Leukemia 1. Etiology—Excess production of white blood cells, causes decreased function of WBCs, RBCs, and platelets 2. Signs and symptoms—Increased infection, anemia, bleeding, bruising, fatigue, weight loss 3. Diagnostic tests—CBC, genetic testing, bone marrow biopsy 4. Treatment—Depending on the type of leukemia, -chemotherapy, stem cells, bone marrow transplant D. Hodgkin’s disease 1. Etiology—Cancer of lymph nodes, affecting white blood cells—most common in people 5–35 years of age 2. Signs and symptoms—Painless swelling of lymph node is early symptom (often in the neck), fever, night sweats, weight loss, weakness, fatigue, and itching. Respiratory symptoms may occur with chest involvement 3. Diagnostic tests—Biopsy, various types of x-rays, ultrasounds, and lymphangiograms 4. Treatment—Possibly chemotherapy and radiation depending on age and stage E. Rheumatoid arthritis (RA) 1. Etiology—Destruction of joints by immune system 2. Signs and symptoms—Swollen painful joints, fatigue, anemia, cardiovascular abnormalities 3. Diagnostic tests—Blood tests, imaging studies 4. Treatment—DMARDs, BRMs, and lifestyle changes. Difficult to treat effectively F. Lupus 1. Etiology—Destruction of many different body tissues by immune system 2. Signs and symptoms—Swollen painful joints, fatigue, anemia, cardiovascular abnormalities 3. Diagnostic tests—Blood tests, imaging studies 4. Treatment—DMARDs, BRMs, and lifestyle changes; difficult to treat effectively G. HIV/AIDS 1. Etiology—Infection of Helper T cells by HIV causing decreased numbers of T cells, eventually leading to severe immune deficiency 2. Signs and symptoms—Flulike symptoms in early stages, -opportunistic infections and some forms of cancer in -full-blown AIDS 3. Diagnostic tests—Medical history, very low helper T cell counts; AIDS diagnosis made when helper T cell counts are less than 200 cells/uL3 4. Treatment—Drug cocktails designed to prevent infection from progressing to full-blown AIDS, treatment of opportunistic infections when they develop H. Severe combined immune deficiency (SCID) 1. Etiology—Severe decreased T cell production (and sometimes other cells) caused by a number of different genetic defects 2. Signs and symptoms—Repeated opportunistic or severe -infections in babies, fatal if untreated 3. Diagnostic tests—Genetic testing 4. Treatment—Depending on the underlying genetic problem: enzyme replacement, complete sterile environment, bone -marrow transplant, stem cells, . Most types -difficult to treat I. Allergies 1. Etiology—Overreaction of the immune system to typically harmless antigens, such as mold, pollen, or animals 2. Signs and symptoms—Depending on severity: upper -respiratory symptoms, asthma, skin rashes, anaphylaxis 3. Diagnostic tests—Medical history, elimination of suspected culprits, skin tests, blood tests 4. Treatment—Avoidance, antihistamines, allergy shots, -steroids, epinephrine