4-21-10 The Immune System-color

4-21-10 The Immune System-color - Clicker Question Which...

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Unformatted text preview: Clicker Question Which Which of the following process(es) that occur(s) at a synapse could be targeted by a drug designed to treat mental illness? A) Secretion of the neurotransmitter B) Binding of the neurotransmitter to a receptor C) Degradation of the neurotransmitter D) Re-uptake of the neurotransmitter ReE) All of the above and more • Last time I discussed… Where are we? • This time I will discuss… – that before the introduction of psychopharmacology, mentally ill patients were treated barbarically. – the brain is a trillion cauldrons of chemical activity in which neurotransmitters in the synapses regulate the transmission of electrical signals. – how psychopharmacological drugs influence the concentration of neurotransmitters in the synapses. – that while we understand a lot about the physico-chemical physicoprocesses that take place in the brain, we still do not understand the mechanism of normal and abnormal thinking and the way the psychopharmacological drugs work. – immunity—how the body protects itself from invaders. immunity— protects – the innate immune system. – the acquired immune system that, like the nervous system, can learn, remember and recognize self from non-self. learn remember recognize non- The human body is capable of resisting many harmful disease-causing agents diseasein the course of everyday life. • Not everyone in a family, dorm, sorority, fraternaty or classroom is equally or classroom is equally resistant resistant to disease. Luckily, immunity (from immunity immunis the Latin word immunis meaning “free of”) against disease can be conferred to sensitive people though vaccinations vaccinations. The Ancients Realized that Survivors of a Disease were often Immune to Getting that Disease Again • In 429 BC, Thucydides noticed • • that smallpox survivors did not get re-infected. reIn the 10 century also In the 10th century, also realizing realizing that survivors of small pox were immune to the disease, Chinese doctors put the fluid from small pox pocks into the noses of susceptible people to protect them from small pox. Puritans Puritans Learned that Africans also Inoculated People to Make them Immune to Small Pox • Lady Mary Wortley • In 1706, the Puritan minister, • Cotton Reverend Cotton Mather, learned from a slave named Onesimus Onesimus, that he had been inoculated inoculated with small pox as a child in Africa as a protective measure. Courageously going against the Church and State, in 1721, during the small pox epidemic in Boston, Cotton Mather and Dr. Zabdiel Boylston inoculated the people. • • Montagu (1721), the wife of the British Ambassador to Turkey, brought back to England a method of preventing the deadly small small pox disease. Physicians would take a small amount of pus from small amount of pus from the the pocks of a person with a mild case of small pox and rub it in to a scratch in the arm of a healthy person. Unfortunately, the healthy patient often contracted a full blown case of small pox and died. 1 Edward Jenner milkmaids he treated noticed that people who got cow pox (variolae vaccinia) were immune to the deadly small pox. One day, when Sarah Nelmes Sarah came to him with cow pox, he decided to see if inoculating decided to see if inoculating someone someone with cow pox would prevent them from getting small pox. He took pus from Sarah Nelmes’ pocks and rubbed it into James scratches in James Phipps’ arm. The 8 year old son of the gardener developed cow pox. Once he was over the cow pox, Jenner exposed him repeatedly to small pox, but he had become immune immune to the small pox virus. virus Jenner (1798) and many A Profile in Courage: Edward Jenner Profile • Jenner reported his results to Royal the Royal Society; however, Sir Joseph Banks, the president of the Royal Society suggested that he should not risk his he reputation by presenting reputation by presenting something "so something "so at variance • Thankfully Jenner used his with established knowledge". meager savings to publish his work privately and within a few years vaccinations for small pox became common practice. Cholera: Cholera: A Bacterial Infection • Cholera iis transmitted from s person to person by the fecalfecaloral route resulting from resulting drinking water contaminated with feces that contain the bacterium, Vibrio cholerae. Vibrio Vibrio secretes a toxin into the secretes toxin into the intestine intestine that results in massive diarrhea followed by dehydration dehydration. If the patient is not rehydrated rehydrated orally or and/or intravenously within hours of being infected, death can result. result. Cholera can also be prevented by a vaccine. vaccine Louis Pasteur Had a Prepared Mind • Louis Pasteur (1880) reasoned that if a vaccine could be found for small pox, then a vaccine could be found for all diseases. Pasteur found a vaccine against chicken chicken cholera by chance. chance One of his colleagues had hi inoculated inoculated chickens with chicken cholera bacilli from an old culture old culture and the chickens did not get sick. not Even when he exposed these these chickens to fresh chicken cholera bacilli that would kill other chickens, the chickens who were exposed to the old strain first still did not get sick. • • • • 2 Louis Pasteur Had a Prepared Mind • Pasteur reasoned that reasoned the potency to cause cholera in chickens had attenuated in attenuated in the old culture. He guessed that the chickens used the hi use th Anthrax Anthrax • • Pasteur pioneered the use in the fresher culture. weaker germs to form a defense against the more powerful germs • Anthrax is often a fatal disease characterized by hemorrhaging and tissue decay. of attenuated bacilli for vaccinations vaccinations, a word he coined in honor of Jenner. • It is caused by a toxin produced by Bacillus Bacillus lungs, skin or intestines. anthracis, which can enter the body through the Louis Pasteur and Anthrax • Pasteur (1881) aged cultures of anthrax anthrax to weaken them and used the weakened germs to make a vaccine. Rabies • The idea that germs could seemed unbelievable and Rossignol, the editor of The Rossi Veterinary Press, challenged Pasteur to a public test. Pasteur inoculated twenty five sheep with his vaccine while twentytwenty-five were not. Subsequently, all fifty were injected with anthrax. Those injected with the vaccine lived while those that were not inoculated died within two days. make an animal healthier • • • Rabies is a fatal disease characterized by the • Rabies is caused by the rabies virus, which is found in • Rabies is often transmitted by a bite. the saliva of an infected animal. inflammation of the brain. Louis Pasteur, Joseph Meister, Human Experimentation and Rabies • Pasteur injected healthy dogs with aged rabies germs (viruses) from the spinal cord of rabid rabbits. The vaccinated dogs became immune to rabies. A 9 year old boy named Joseph Meister Meister was bit by a rabid dog. Since the boy would have died had he been left untreated, Pasteur (1885) reluctantly took the risk on treating Joseph Meister with the vaccine that had only been tested on dogs. Happily, the vaccine worked and the boy survived to become the caretaker of the Pasteur Institute. Pasteur’s Father and Mother Painted by Louis Pasteur, Himself • • 3 The Wisdom of the Body in the Fight Against Infectious Diseases The Body’s First Line of Defense: Innate Immunity • Skin and the mucosa lining the digestive and urogenital mucosa • • tracts are physical barriers to disease, although a tiny cut will allow pathogens to enter the body. Sweat, saliva and tears contain lysozyme, an enzyme saliva tears lysozyme that degrades the cell wall of gram positive bacteria. This deg ce pos bacte causes the bacteria to lyse. Lysozyme was discovered by Alexander Fleming in 1922. The respiratory tract is guarded by the hairs in the nostrils hairs mucus cilia as well as the mucus that traps microbes and cilia that sweep the mucus out of the respiratory system and down the esophagus. The hydrochloric acid produced by the parietal cells in the hydrochloric Helicobacter stomach kills microbes (with the exception of Helicobacter) that come from the respiratory system or enter the body along with food. The body protects itself from infectious microbes in two ways: – Innate Immunity (skin, phagocytes, interferon) – Acquired Immunity (B and T lymphocytes) • The The Inflammatory Response: Phagocytes and Pus • Microbes that breach the first line of defense are accosted by the white white blood cells which are found in the blood, the interstitial fluid, and the lymph. fluid, and the lymph. The white blood cells that white engulf microbes by phagocytosis phagocytosis are known as phagocytes phagocytes. The neutrophils, neutrophils which are a kind of phagocyte phagocyte that most rapidly fights infections, make up most of the pus pus that occurs with an infection. nobelprize.org/educational_games Ilya Mechnikov In 1882, Ilya Mechnikov was studying the larvae of starfish. He noticed that when he inserted a splinter into the larva, strange cells gathered at the point of insertion. The cells surrounded the splinter, eating any foreign substances that entered through the ruptured skin. Mechnikov named these new cells phagocytes from phagocytes the Greek words “eating cells.” • Splinters “Sharp splinters were introduced into the bodies of these Bipinnaria and the next day I could see a mass of moving cells surrounding the foreign bodies to form a thick cushion layer. The analogy analogy between between this phenomenon and what happens when a man has a splinter that causes inflammation and suppuration is extraordinary.” Disease: A Fight Between Microbes Disease: and Phagocytes • This observation led Mechnikov to propose that in humans, phagocytes move to the wound and engulf the bacteria. • “…disease would be a fight fi between between the morbid agent, the microbe from outside, and the mobile cells of the organism itself. Cure would come from the victory of the cells and immunity would be the sign of their acting sufficiently to prevent the microbial onslaught.” 4 Ilya Mechnikov “Photographs taken of him when he was working at the Pasteur Institute show him with long hair and an unkempt beard. It is said of him that at this time he usually wore overshoes in all weathers and carried an umbrella, his pockets being overfull with scientific papers, and that he always wore the same hat, and often, when he was excited, sat on it.” The The Inflammatory Response The Inflammatory Response • When the skin is broken, damaged mast mast cells cells release histamine (which causes one histamine to burn and itch). The histamine diffuses to burn the capillaries and cause them to dilate capillaries dilate and become leaky. leaky The phagocytes and components of blood plasma move out of the leaky capillaries. This results in redness and swelling. The redness swelling puts pressure on the pain receptors. Consequently, the inflammation leads to pain pain. In the interstitial fluid, the phagocytes phagocytes known as neutrophils rapidly engulf neutrophils rapidly engulf microbes and dead or injured body cells. The pus at the site of injury consists mostly pus of interstitial fluid and dead neutrophils. interstitial dead Stinging Nettle Causes Inflammation Because It Contains Histamine • The hairs of stinging stinging • nettle contain contain histamine, acetylcholine and serotonin. These molecules that These molecules that occur occur in the plant and animal kingdoms cause itching, burning, reddening and swelling when you touch the hairs of the plant, informing you that the plant you touched is Urtica Urtica dioica. • • • Phagocytes, Antioxidants and Free Radicals • The phagocytes kill the invading bacteria by producing a dose of free free radicals (including superoxid ), which are ide id produced by the phagocyte itself. Vitamin C is necessary antioxidant to as an antioxidant to protect the phagocyte from its own high dose of superoxide. Corticosteroids and Anti-Inflammation Anti• Cortisol released during stress suppresses suppresses the inflammation response. In the short term, this minimizes minimizes the pain associated with • • inflammation; but in the long term it inflammation; but in the long term, it makes makes it easier to succumb to succumb germs. Synthetic corticosteroids (hydrocortisone) are used topically topically to to treat the pain and itchiness of dermatitis, dermatitis, eczema, psoriasis, hemorrhoids, and poison ivy or nasally nasally to to treat allergy symptoms. 5 Zits • Acne occurs during puberty when androgens androgens • • • • produced by the adrenal glands in men and adrenal women stimulate secretion of oils from the sebaceous (oil) glands beneath the skin. The oil glands, which are exocrine glands, exocrine continuously secrete oil in order to lubricate the skin the skin. Cells that are close to the opening of an oil gland block the duct and cause a buildup of oil Bacteria beneath the skin. Bacteria feast on this oil and trigger the inflammation response. inflammation If the inflammation is near the surface, you get pimple and boil a pimple and if it is deeper, you get a boil. When the oil breaks though to the surface, you whitehead and get a whitehead and the oil becomes oxidized, it turns black and you get a blackhead blackhead. Causes and Preventative Measures • The three basic causes of acne – Oil from sebaceous glands – Clogged pores – Bacteria • Three preventative measures – Minimize oil (wipe away with mild astringent; or kill oil producing cells with laser). – Unclog pores (soap and water; alphaalpha-hydroxy acids or betabetahydroxy acids) – Kill bacteria (benzoyl peroxide) AlphaAlpha-Hydroxy Acids Glycolic acid (from sugar beet and sugar cane) Lactic acid (from milk) BetaBeta-Hydroxy Acids • Salicylic acid, isolated from the bark of willow (Salix) trees and Spiraea bushes, is Spiraea involved in the “systemic immune response” of plants. immune response of plants Notice the greater proportion of CH bonds in this betabetahydroxy acid than in the alphaalpha-hydroxy acids. This makes salicylic acid more soluble in oil (more nonpolar) so it penetrates more deeply into the oil ducts. • • Innate Immunity Against Viruses: Interferons • Interferons are proteins that are produced by virus-infected viruscells that help other cells become resistant to resistant viruses. The interferon gene from the gene infected cell is transcribed transcribed and translated and translated to make interferon, which is secreted secreted from the cell and diffuses to the neighboring healthy cells. The interferon stimulates the healthy cells to make antiviral antiviral proteins. • • 6 Recombinant DNA Technology Makes Interferon Cheap and Accessible for the Treatment of Hepatitis and other Viral Infections Our Blood—Our Identity Blood— • Experience with blood transfusions • • indicate that our body can distinguish between our own blood and the blood of others. Karl Landsteiner found that the red red blood cells in the blood seemed to blood cells in the blood seemed to fall fall into four groups (A, B, AB and O). Jean Dausset, Baruj Benacerraf and George Snell found that the white white blood cells (as well as all the other cells in our body) also have proteins, now known as the major histocompatibility complex, in their plasma membranes that represent our self. self Karl Landsteiner (1930): Our Blood and Our Biological Individuality • Anthropological Studies – Northern Europeans are mostly Type A. – Asians are mostly Type B. – American Indians are mostly Type O. – Tests of blood found at a crime scene has been used to acquit innocent people. – Blood tests has been used to exclude a putative father. Karl Landsteiner • Forensic Studies • Paternity Tests Jean Dausset, Baruj Benacerraf and George Snell John John Galbraith Simmons: The Self “The self is not just a narrative fiction of language and mind, nor is a physical structure its only The boundaries. The self may also be said to exist on a molecular level, comprised of a group of antigenic proteins found found in all cells of the body. The specific complexion of these antigens is configured by a set of genes known as the “major histocompatibility complex” (MHC).” 7 Peter Medawar and Macfarlane Burnet: Acquired Immunity (1960) • If the innate defenses can not eliminate an • The immune system provides acquired acquired immune infection, the immune system kicks in. immunity, consisting of humoral humoral immunity and cell mediated immunity and cell-mediated immunity immunity. • Whereas the innate system may be innate effective before one is exposed to a before immune microbe, the immune response develops after after exposure to microbes. Peter Medawar (1946): The Uniqueness of the Individual “Philosophy and common sense, though often parted, have long agreed about the uniqueness of individual man. Different men have different faces, sizes, shapes and origins; different aptitudes, skills and predilections; and skills and predilections; and different ambitions, hopes and fears. Science now makes it a trio of concordant voices, for the uniqueness of individual mice and men is a proposition which science can demonstrate with equal force, perhaps with deeper cogency, and certainly with a hundred times as much precision.” • The immune system is triggered by an host’s body. antigen antigen, a molecule that is foreign to the Books by Peter Medawar Books by MacFarlane Burnet Clonal Selection Theory How does the immune system recognize so many different foreign particles, mobilize against them and remember them? MacFarlane Burnet suggested MacFarlane Burnet suggested that that it “would make real sense if Antigens Generate the Proliferation of Gen Anti Antibodies • Proteins that make up the coats of • • • • viruses, the surfaces of protozoa and antigens. other parasites act as antigens. Carbohydrates from the walls of bacteria and fungi also act as antigens and fungi also act as antigens. Various venom and toxins that get into venom toxins the blood stream also act as antigens. Vaccines act as antigens. antigens Unfortunately, proteins from the surface donated of donated blood cells, tissues and antigens organs also act as antigens. cells cells produced a characteristic pattern of globulin [antibody molecule] for genetic reasons and were stimulated stimulated to proliferate by contact with the corresponding antigenic determinant.” 8 Antigen: Antibody-Generating AntibodySubstance • An antigen triggers the immune system to antigen • • antibody that produce large quantities of the antibody that will bind to it. An antibody is protein found in the circulatory An antibody is a protein found in the circulatory specifically system system that specifically binds to an antigen high with high affinity. The immune system, like the brain, learns learns about the antigens to which a host is exposed memory and has a memory which allows it to react rapidly against an antigen it has experienced before. Antibodies • An antibody has two identical antigen binding sites that two • • allow it to form large complexes with antigens or microbes with exposed antigens. This process of forming large complexes is called agglutination agglutination. Macrophages are a kind of phagocyte that engulfs the insoluble agglutinated complexes of antigens and/or microbes phagocytosis in a process called phagocytosis. Paul Paul Ehrlich (1908) chemical bond which, in view of the strict specificity is most easily specificity is most easily explained explained by the existence of two groups of distinctive configuration - of groups which according to the comparison made by Emil Fischer fit each other ‘like ‘like lock and key’.” The antigen and the “…enter antibody “…enter into a AntibodyAntibody-Antigen: Lock and Key • The part of the antigen that the • • • • • antibody recognizes is called the antigenic antigenic determinant or epitope epitope. The antibody has amino acids with amino chemical the correct chemical properties to epitope bind the epitope. If the epitope be positively positively charged, charged, the binding site will be negatively charged. negatively charged. If the epitope be negatively negatively charged, charged, the binding site will be positively positively charged. If the epitope be polar, the binding polar site will also be polar. polar If the epitope be nonpolar, binding nonpolar site will be nonpolar. nonpolar The Complement System “Complements the AntibodyAntibody-Macrophage System” • The complement complement recognize the antibodies when they bind to an antigen on antigen on a microbe. microbe. The complement proteins poke poke B (bone marrow) Cells and T (thymus) Cells • The cells that produce antibodies are antibodies • • called lymphocytes. They are derived lymphocytes from lymphocyte stem cells. lymphocyte The lymphocyte stem cells are derived pluipotent from pluipotent stem cells in the bone marrow bone marrow. Lymphocytes that mature in the bone marrow are known as B cells. cells. Lymphocytes that move to the thymus and mature there are known as T cells cells. The mature B and T cells enter the lymphatic lymphatic system and go to the spleen lymph spleen, lymph nodes, tonsils, tonsils adenoids adenoids and appendix. appendix proteins • holes in the plasma membrane of the microbe and the microbes die. • 9 The Lymphatic System • The lymphatic system is an open open that returns fluid from the interstitial fluid back to the circulatory system system. When the lymph fights a large microbe attack, the lymphocytes and lymphocytes and Humoral Immunity: B cells • B cells, with antibodies antibodies on their surfaces, travel through the circulatory and circulatory and lymphatic lymphatic systems. The B cells also conducting system • • secrete secrete antibodies that circulate in the blood stream, interstitial fluid and lymph. macrophages macrophages accumulate in the lymph glands and one gets “swollen glands.” Susumu Tonegawa (1987): Generation of Immune Diversity by Splicing Distant Segments of DNA How can lymphocytes create antibodies to millions of antigens when there are approximately 2020-30 thousand different genes in person? in a person? Susumu Susumu Tonegawa discovered that, in each lymphocyte clone, the antibody genes are antibody formed by splicing segments of DNA in a unique way. By recombining segments of DNA, millions of genes and antibodies can be created. Revolutionary Revolutionary Idea Before Susumu Tonegawa obtained experimental evidence that the DNA that encodes a single polypeptide in an antibody occurs in two widely separated regions of the genome in non-lymphocyte cells, this revolutionary theory, originally proffered by W. J. Dreyer and J. Bennett in 1965, was not taken seriously because it contradicted two of the most widely accepted dogmas of biology: – one gene encodes one polypeptide – the genome is constant during ontogeny and cell differentiation 10 B Cells • When a B cell develops, its antibody gene is gene transcribed transcribed, the mRNA is translated and the translated resultant antibody proteins move through the antibody proteins B Cells • There are • • millions of different kinds of B cells. Each B cell produces a different antibody. B cells that have the antibody to an antigen that enters the body become activated activated. • • secretory system until 100,000 of them become incorporated into the plasma membrane. These antibodies, which can be considered receptors receptors for antigens, stick out of the plasma membrane. Some of the antibodies produced are in the in exocytotic vesicles and are not incorporated into the plasma membrane, but are secreted from secreted from the B cells into the blood (one of the four humors humors). B Cells • The activated B cells divide to produce plasma plasma cells and memory memory cells. The memory memory cells have the cells have the antibody antibody on the B cell cell surface. The plasma cells plasma live for 4-5 days producing and secreting a given antibody at a rate of 2000 molecules per second. B Cells Cells The memory memory cells, which live as long as the person does, are po poised to divide into plasma cells that will rapidly produce antibodies and memory cells following a later exposure to the same antigen. • • Only B Cells that Encounter their Antigen Propagate Every minute our body produces several million lymphocytes—each one lymphocytes— expressing its unique antibody. If a B cell encounters its antigen, it will divide to form plasma cells and memory cells, which will last a lifetime. If a B cell does not encounter its antigen, it will die. die. Memory Cells and Acquired Immunity • Acquired results from the buildup of memory cells in in your body. bod The number of types of B memory cells your body has depends on prior exposure to various antigens. immunity • “After “After the great randomized gene lottery natural selection will pick the winners, thereby generating specific immunity, the cheapest and most efficient protection there is against infections.” infections.” 11 Childhood Immunity • A mother’s antibodies, but not her mother’s placenta placenta from mother to child. Her antibodies antibodies and macrophages are macrophages passed through her breast milk. breast lymphocytes, are passed through the Dropped Pacifiers, Dirty Hands and Faces • Exposure to some amount germs of dirt and germs during childhood primes the primes immune system so that immune system so that the the secondary immune response is armed and ready. Antibacterial soaps kill germs, but they also • These antibodies provide a child with Th • While the child is immune, he/she can immunity immunity to many germs, including polio. come in contact with these germs and build up his/her own acquired acquired immunity, so that an infection will be fought in the child for the rest of his/her life by the powerful secondary immune secondary response and he/she would not even realize they were infected. • slow slow down the priming of the immune system. How Polio Became a “Disease of the Clean” • Polio is a contagious disease. • The polio virus enters the body through the mouth and leaves mouth feces the body in the feces. By not flushing the toilet or washing one’s hands, the polio virus can be transferred between infected and uninfected people by the fecalfecal-oral route. There was a polio epidemic in the United States in the 1950s. • • Consequently, health officials and scientists recommended good sanitary practices to prevent the spread of polio. 12 How Polio Became a “Disease of the Clean” • However, the recommended sanitary washing measures, including washing one’s cleaning hands, cleaning ones house and polio virusensuring a polio virus-free water prevents supply, prevents a child from developing acquired immunity to the polio virus while still being the protected by his/her mother’s antibodies. Consequently, a child or an adult, who has lost the protection of the maternal antibodies, but had not developed his/her own acquired immunity, could easily come down with polio. Consequently, polio predominantly infected those who followed the new sanitary guidelines. • • Polio Vaccines Virtually Eradicated Polio • Jonas Salk found that humans became virus. immune to the polio virus when they were “formaldehydeinjected with a “formaldehyde-killed” Eckard Wimmer (2002), who was Driven by Curiosity, Created a Synthetic Poliovirus that is Identical to the Natural Virus “Research on viruses is driven not only by an urgent need to understand, prevent, and cure viral disease. It is also also fueled by a strong curiosity about the minute particles that we can view both as chemicals and as “living” entities.” Should Scientists Create Synthetic Disease-Causing DiseaseViruses? • Albert Sabin found that people became • immune to the polio virus after eating a lump of sugar containing a live attenuated virus. The dead virus tt Th vaccine could be prepared quickly, but it took a while to find the conditions that would yield a live virus that could enter the body through the digestive system by itself and was safe. The live-attenuated virus has an liveadvantage in that it easily passes from the immunized person to his/her family and friends by the fecal-oral route resulting in fecalthe immunization of many people. Comic Book about Polio Vaccines Allergies • Allergies are an overreaction to common environmental antigens. Allergic Response • Antigens that cause (or generate) • allergies are known as aller allergens. When a person is first exposed to an allergen, the allergen binds to the B cell with a complementary cell receptor. The activated B cells divide to form plasma cells which secrete antibodies to the allergen. • These antibodies bind to receptors on Mast cells. Mast • When the antibodies on the mast cell recognize and histamine bind the allergen, the mast cells secrete histamine, inflammation which triggers the inflammation response. 13 Antihistamine • Histamine released from mast damaged mast cells causes blood capillaries to become leaky so the phagocytes can get to the region where the cells are damaged. In the case of allergies, allergies histamine histamine released from mast mast cells does the same thing, but the fluid is just a nuisance nuisance causing nasal causing nasal irritation and watery eyes. The Histamine Receptors in the Stomach Differ from those in Blood Vessels • Histamine increases the • James Whyte Black discovered that antihistamines, antihistamines, which successfully block the allergic reactions do not block the allergic reactions, do not inhibit inhibit the production of' gastric acid because the histamine receptors in the stomach (H-2 (Hreceptors) are different. production of gastric acid. • • Antihistamines block the • Histamine-2 receptor blockers, Histamineincluding Tagamet, Zantac and Tagamet, Pepcid are effective treatments for ulcers. histamine receptor on the capillaries and consequently reduce the release of fluid. Anaphylactic Shock • When a person is allergen (e.g. peanut protein, bee venom and penicillin), an exposure to the antigen will cause all their mast cells to release all their mast cells to release histamine histamine simultaneously. This will cause all the capillaries to become leaky and the blood blood CellCell-Mediated Immunity: T Cells hypersensitive hypersensitive to a given • • Anaphylactic shock can be pressure will suddenly and drastically drop. • T cells proliferate into cytotoxic T cells, Helper T cytotoxic cells and memory T cells. thwarted by injecting adrenaline adrenaline into the patient. • Cytotoxic T cells recognize and destroy the body’s body’s cancerous own cells that have become infected or cancerous. Cytotoxic T Cells Helper T Cells • Cytotoxic T cells bind to body’s cells that have a body’s that nonnon-self antigen bound to the surface. • The cytotoxic T cells then synthesize and secrete a • The macrophages that digest microbes interact with macrophages • the rest of the immune system. They have receptor proteins that bind the antigen from the microbe. The antigen-receptor complex then migrates to the antigensurface of the macrophage. number of deadly proteins, one of which is known as perforin perforin, a protein that kills the infected host cell by making holes in its membrane. 14 Helper T Cells Interleukins (or Cytokines) • The macrophage secretes a protein known as • The Helper T cell, once bound to the Helper T cell to the macrophage. interleukininterleukin-1 that promotes the binding of the • Helper T cells have receptors that bind to the bind macrophage receptormacrophage receptor-antigen complex. • Each Helper T cell has only one type of receptor that recognizes only one macrophage receptor-antigen receptorcomplex. • macrophage receptor-antigen complex, secretes tora protein known as interleukin-2, which interleuki activates B cells and T cells to divide in order to form B and T memory cells and more plasma B cells and cytotoxic T cells that can be used right away. The protein is called interleukin because it is involved in communication between (inter) communication white blood cells (leukocytes). InterleukinInterleukin-1 and Fever • Interleukin-1 travels to the Interleukin• • change the set-point for your body settemperature higher than 98.6 ̊ F. 98. Even though you have a fever, you feel cold when your temperature feel cold when your temperature is is less than the temperature of the setset-point. When you have a fever, your fever blood is diverted from the skin to the core of the body to heat up the core. You also shiver to heat up your body core. All this makes you want to bundle up in bed. InterleukinInterleukin-1 Makes you Feel Crummy • Interleukin-1 also causes Interleukinthe hypothalamus to secrete releasing factors that activate the flight or flight response which kills your response, which kills your appetite appetite. InterleukinInterleukin-1 also lowers the threshold of the nerves that carry stimuli from pain sensing neurons to the brain. Consequently, your your joints begin to ache. hypothalamus hypothalamus and causes it to • InterleukinInterleukin-1, Prostaglandins and Aspirin • Interleukin-1 causes fever, loss Interleukinof appetite and pain through a signal transduction chain that involves the synthesis of involves the synthesis of prostaglandins prostaglandins. Luckily, aspirin blocks aspirin prostaglandin synthesis and prevents the crummy feelings caused by interleukin-1 that are interleukinassociated with being sick. The action of Acetaminophen acetaminophen acetaminophen is not well understood. It blocks prostaglandin blocks prostaglandin synthesis synthesis and it may also prevent pain by binding to the • endogenous endogenous cannabinoid receptor in the brain. 15 Recombinant DNA Technology Makes ImmunoImmuno-Boosters (Interleukins) Cheap and Accessible for People with Immune Deficiency Diseases (Although it also makes them feel crummy) HIV Causes a Deficiency in the Immune System • HIV (human immunodeficiency virus), which is the cause of AIDS AIDS (Acquired Immune Deficiency Syndrome), specifically binds to and destroys Helper T Helper cells. The depletion of Helper T cells drastically impairs the body’s ability to fight infections through cell-mediated cellimmune responses. • Severe Combined Immunodeficiency Disease (SCID) • One form of SCID results from the production of a mutant form of adenosine adenosine deaminase (ADA) by B cells and cells. cells and T cells. Some clinical trials are underway to treat this Autoimmune Diseases • An out-of-control immune system out-of• causes trouble when the lymphocytes make antibodies directed against antibodies the body itself. Lupus (→) occurs when the B cells make antibodies against the normal molecules in the body The antibodies molecules in the body. The antibodies can can be directed against a variety of organs. Type 1 diabetes occurs when the insulininsulin-producing cells of the pancreas are the targets of Cytotoxic T cells. Multiple sclerosis occurs when the oligodendrocytes in the central nervous system are the targets of Cytotoxic T cells. • • Other clinical trials have immunodeficiency immunodeficiency disease with gene gene therapy. • • been suspended because the random gene insertions has caused leukemia. leukemia lupus.org Lymphoma and Leukemia • Lymphomas are cancers that occur in the lymphatic system and are caused by malignant lymphocytes (T cells and B cells). Leukemias are are typically cancers that occur in the bone marrow or circulatory system and are caused by other kinds of malignant white blood cells. Development of Lymphoid and Myeloid Cells • [Granulocytes] 16 Biotechnology: Monoclonal Antibodies • A mouse can be injected mouse with an antigen and after it produces antibodies to the antigen, its B cells are isolated cells from its spleen. spleen The B cells are then fused cells with cultured cancer with cultured cancer cells and the fusion cells divide divide often and grow indefinitely, producing an antibody to the antigen injected into the mouse. Biotechnology: Monoclonal Antibodies A monoclonal monoclonal antibody produced this • way can become part of a diagnostic kit to diagnostic detect molecules like detect molecules, like an indicator of pregnancy; or the human human chorionic gonadotropin, which is antibody antibody to HIV, • Single fusion cells are a single kind of antibody. isolated and grown on culture plates. They produce which is an indicator of HIV infection. Cell Cell Mediated Immunity and Organ Transplants • Unless one gets an organ from an identical twin, a transplanted organ will have cells whose surface is coated with antigens that are not recognized as “self” by the recipient’s immune system system. Consequently, the recipient’s Cytotoxic T cells will begin to kill the cells of the donated organ. Luckily, cell-mediated immunity can be cellimmunosuppressant suppressed by the immunosuppressant drugs Cyclosporin and Tacrolimus. These immunosuppressant drugs are important in organ making organ transplants possible. Immunosuppressants are Isolated from Fungi and Actinobacteria Cyclosporin is produced by the fungus, Tolypocladium the inflatum. Tacrolimus is produced by Streptomyces Streptomyces tsukubaensis. the Actinobacterium, • • Individuality: How Our Blood Defines Us • Agglutination or clumping will occur if the blood contains antibodies and antigens that bind to each other. • Blood Group A (A antigen on can donate to A and AB). to and AB • Blood Group B (B antigen on can donate to B and AB). • Blood Group AB (A and B Aside: Abraham Lincoln Contracted Small Pox Just Before He Delivered the Gettysburg Address This portrait of President Abraham Lincoln was taken Lincoln was taken on on November 8, 1863 by Alexander Gardner eight days before he delivered the Gettysburg Address. RBCs, B antibody in blood serum— serum— RBCs, A antibody in blood serum— serum— • antigens on RBCs, no antibodies in blood serum—universal serum— recipient). Blood Group O (No antigens on RBCs, A and B antibodies in blood http://nobelprize.org/educational_games/ serum— serum—universal donor). 17 Abraham Lincoln at Gettysburg Abraham Lincoln Probably Had a Mild Case of Small Pox While He Delivered his Address at Gettysburg on November 19, 1863 • Dr. Washington van Bibber told Abraham Lincoln when he • • returned from Gettysburg that he had "a touch of the varioloid." varioloid." Lincoln responded: "Then am I to understand that I have the small pox?” small pox?” Van Bibber nodded his head, “yes”. Lincoln responded, "How interesting. I find every now and then that even unpleasant situations in life have certain compensation. As you came in just now, you passed through a room full of people. Do you have any idea what they are there for…they are there, every mother's son of them, for one purpose only: namely, to get something from me. For once in my life as president, I find myself in a position to give everybody something!" rmc.library.cornell.edu While Lincoln Survived Small Pox, William H. Johnson, Lincoln’s Valet, Was Not as Lucky William H. Johnson, Lincoln’s valet, traveled with him to Gettysburg. Johnson died of small pox two months later, and was buried at what is now Arlington National Cemetery. 18 ...
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