{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

4-21-10 The Immune System-color

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

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

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 anti...
View Full Document

{[ snackBarMessage ]}