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Topics 6.3 & 11.1 The Boy in the Bubble David Vetter = born Sept 1971 His parents had a first son (also named David) that was born the year before, but died after 6 months because of SCID – severe combined immunodeficiency SCID – body is unable to produce wbc to fight off foreign invaders The disease is X linked, meaning that there is a 50% chance that a Vetter male child would have SCID When their second son David was born, he also had SCID and was placed in a “plastic bubble” 10 seconds after birth to keep him in a sterile environment away from foreign invaders. He lived in the bubble for 12 years Doctors hoped to cure him with a bone marrow transplant from his healthy sister. Unknown to doctors, Katherine had a virus in her marrow. When David received the transplant, the virus caused mononucleosis, and eventually grew out of control and lead to Burkett's lymphoma (a type of cancer) Knowing that he was dying, he spent his last few days of life outside the bubble. http://www.bing.com/videos/search?q=boy+in+the+bubble+disease&FORM=HDRSC3# view=detail&mid=4FD8CDA29BAB681AF9F44FD8CDA29BAB681AF9F4 Pathogen A pathogen is an organism or a virus that causes a disease in any other organism. I.e.: Bacteria, fungi, viruses Exposure to the majority of pathogens does not result in a disease because We can prevent pathogens from entering our bodies We can develop an immunity to particular pathogens We can use chemicals (i.e. antibiotics) to defend ourselves. Viruses Non cellular structures Contain DNA or RNA surrounded by a protein coat. Not considered to be a living cell because they cannot undergo essential life process on their own (i.e.: replication or protein synthesis) (When a virus wants to replicate, it enters an (unwilling) “host” cell and uses the host’s enzymes to replicate its DNA. It takes away energy and resources from the host cell.) HPV EBOLA Polio Rabies Viruses and antigens Viruses will have antigens on its protein coat/cell membrane. All viruses must find a type of cell in the body that matches their own proteins in a complementary way so it can enter the cell (through endocytosis) This is why only certain body cells are damaged by certain viruses as is typically reflected in the symptoms associated with the infection. Bacteria Prokaryotic cells, that can rapidly duplicate A colony of bacteria can obstruct regular function in the host organism Bacteria products can cause unpleasant side-affects to a host organism. Streptococcus H. pylori Antibiotics Antibiotics are chemicals that may be used to fight off bacterial infections. Antibiotics often work by disrupting the ability of the bacterium from replicating and/or undergoing protein synthesis. (If they cannot undergo protein synthesis, they will lack the essential proteins for life – and thus die) (If they cannot replicate, the colony will not be able to increase in number and eventually the body’s immune system will be able to kill the remaining bacteria) Antibiotics Antibiotics do not disrupt cell function in your cells because bacteria cells are prokaryotic and you are made of eukaryotic cells. They are different enough that it doesn’t have an effect on your cells. Why can’t antibiotics be used to kill viruses? Viruses don’t undergo replication or protein synthesis on their own so there is nothing to disrupt. Antibiotics Antibiotics are often derivatives of fungus such as penicillin (which comes from the fungi Penicillium) If fungi and bacteria are competing for the same food source, and the food source becomes scarce penicilllium will release antibacterial antibiotics (penicillin) Testing Penicillin (p307) In 1928, Scottish scientist Alexander Flemming (accidently) discovered penicillin. In the 1930’s, scientists Howard Florey and Ernest Chain investigated the use of penicillin. Testing Penicillin Penicillin killed bacteria on agar plates but they wanted to know if it could be used to control bacterial infections in humans. They first tested it on mice 8 mice were deliberately infected with a streptococcus bacteria that causes death from pneumonia. 4 of the mice were given penicillin injections. Within 24 hours, the 4 untreated mice were dead but the 4 given penicillin were healthy. (2) 4 of the mice were given penicillin. The other 4 were not. (1) 8 Mice are given streptococcus 24 hours later…. (3) The mice given penicillin recovered and lived. The mice that were untreated died. Testing Penicillin They next conducted human trials. The 1st human test subject was a 43 year old male with an acute, life-threatening bacterial infection He was given penicillin for four days and his condition improved considerably. Unfortunately, supplies of penicillin ran out and he suffered a relapse and died from the infection. Testing Penicillin Larger quantities of penicillin were produced and they tested it on 5 more patients with acute infections. All were cured of their infection. (Unfortunately, one of the patients died from a brain hemorrhage brought on by complications from the initial infection, however, the infection was cured) Pharmaceutical companies in the US began producing penicillin in larger quantities allowing for more extensive studies, confirming it’s use as a highly effective treatment for previously incurable bacterial infections Testing Penicillin p 308 Florey and Chain’s test on the safety of penicillin would not be compliant with current testing protocols. They tested the drug on human patients after a very brief period of animal testing – there could have been severe side effects The samples they used were not pure and there could have been side effects from the impurities. Testing Penicillin p308 On the other hand, the subjects they used all had severe infections and were on their death beds. They were cured as a result of the experimental treatment. And because of the expeditious, risk-taking testing, penicillin was used to treat wounded soldiers on DDay (June 1944) and the number of deaths from bacterial infections was greatly reduced. Resistance to Antibiotics Some strains of bacteria have evolved genes giving them resistance to antibiotics and some strains of bacteria have multiple resistance. If a bacterium is resistant to one antibiotic, its not too big of a problem. If a strain develops multiple resistance, that can be concerning. How to Prevent Antibiotic Resistance Antibiotics should only be prescribed for serious bacterial infections. Patients must complete the prescribed course of antibiotics to eliminate infections completely. High standards of hygiene require at medical facilities to prevent cross-infection. Farmers shouldn’t use antibiotics in animal deeds to stimulate growth Pharmaceutical companies need to develop new types of antibiotics (*no new types have been introduced since 1980s) Fungi Parasites 1st Line of Defense The first line of defense against foreign invaders is mainly physical The skin and the mucous membranes defend against foreign invaders. The skin provides a physical barrier like a wall preventing pathogens from getting in. The Skin The epidermal layer is constantly being replaced as underlying dermal cells die and are moved upwards. The epidermal layer is mainly dead cells and thus is a good barrier because it is of no use to viruses. Sebum The sebaceous glands produce a chemical called sebum The sebum provides moisture It is also an acidic secretions (pH 3-5) which inhibits the growth of microbes Mucous Membranes Weak points in our defense against foreign invaders are areas in which we are not protected by skin. Mucous membranes secrete a mucus, which is a sticky solution of glycoproteins. Mucus may help in these areas by trapping micro- organisms and prevent further entry Examples (Mucous Membrane) In the trachea (which leads to the lungs), foreign particles are trapped in mucous or filtered by tiny hairlike structures called cilia that sweep particles to the entrance where coughs can expel them. In the stomach, corrosive acids and digestive enzymes destroy microbes that may be found in food Mucous Membranes The head of the penis, and the inner layer of foreskin have mucous membranes. The vagina produces mucous and has an acidic environment too to protect itself. Lysozyme – an antimicrobial enzyme that is found in tears, saliva, mucous secretion, perspiration will destroy bacterial cell wall killing the bacteria. nd 2 line of Defense Kicks in when the invader takes up residence with in the body. INFECTION: the successful invasion of a pathogen Leukocytes are used to fight off an infection (There are different types of leukocytes. Leukocytes that create make antibodies are called lymphocytes.) Leukocytes are white blood cells (wbc) Found in the blood stream but also in body tissues have a nucleus unlike rbc responsible for responding to foreign invaders and destroying them many different types Bone Marrow – where blood cells are made Carry O2 to cells Produce antibodies Find invaders and initiate attack Involved in blood clotting Macrophage Is a type of wbc that ingests foreign invaders by phagocytosis (Because it undergoes phagocytosis, it is also referred to as a phagocyte) All cells have proteins on their cell membranes called ANTIGENS Antigens act as identity markers. Macrophages recognize body cells of the host by its antigens Foreign invaders will have different cell surface antigens which will cue macrophages to get rid of them Phagocytosis This is the process when wbc ingest invading microbes and chemically destroy them with enzymes Macrophages –have pseudopods which are protrusions that will attach to the surface of an invading microbe, engulf it and digest it with enzymes This is a non-specific immune response because the identify of the pathogen is not determined (at this point) Animations http://www.pennmedicine.org/encyclopedia/em_Disp layAnimation.aspx?gcid=000098&ptid=17 Antibody Also known as an immunoglobulin Soluble proteins that are produced by the immune system as a response to the presence of an antigen Many different types. Produced by different kinds of lymphocyte (each lymphocyte will recognize a particular kind of antigen and produce antibodies against that kind of antigen) Antibodies Attach themselves to antigens of foreign invaders. How does this help destroy pathogens? Role of Antibodies Neutralization of pathogens This will make the foreign invader useless because now they cannot enter host cell (cannot “dock” on host cells Also can neutralize toxins produced by pathogens Role of Antibodies Opsonization Antibodies target pathogens for phagocytosis (by phagocytes) Role of Antibodies Agglutination The “clump” of pathogens cannot enter a host cell Easier target for lymphatic system to filter and phagocytes to ingest. Role of Antibodies Activation of Complement The complement system is a collection of proteins which ultimately lead to the reformation of the membranes of pathogens. Antibodies attach to the surface of antigens causing a pore in the membrane Water and ions enter the cell causing the cell to swell and lyse HIV and the Immune System HIV: human immunodeficiency virus is a virus that infects the cells of the immune system It is a retrovirus: it contains RNA and when it enters a host cell it uses the enzyme reverse transcriptase to make DNA from the RNA. HIV and the Immune System It reduces the number of lymphocytes that are actively involved in the production of antibodies Leads to less antibodies which means the individual will be more likely to develop a disease that would be easily fought off by a healthy immune system HIV Hard to find a cure or a vaccine. HIV hides in its host cell for years Mutates relatively quickly – always changing its antigens making it hard to vaccinate against and hard for body’s immune system to recognize it. The rate of which HIV destroys lymphocytes can be slowed down with antiviral drugs AIDS HIV can lead to AIDS (acquired immune deficiency syndrome) In these cases, HIV has severely weakened the individual’s immune system and their lymphocyte count is particularly low. These individuals are susceptible to illnesses that healthy individuals have no problem fighting off such as the common cold HIV transmission Through: Blood Semen Vaginal secretions Breast milk Most common transmission occurs via: Unprotected sex Sharing of injection needles Mother to child during birth or breastfeeding HIV animations http://highered.mheducation.com/sites/0072943696/ student_view0/chapter14/animation__hiv_replication. html http://highered.mheducation.com/sites/0072943696/ student_view0/chapter14/animation__how_the_hiv_i nfection_cycle_works.html Social Implications of AIDS In 2006, more than 60% of people living with HIV/AIDS were from Sub-Sahara Africa. Of the 3 million people who died from AIDS related diseases in 2006, 2 millions of them were from SubSaharan Africa The number of new infections in North America and Western Europe have either stayed the same or decreased. This is believed to be the result of HIV prevention programs and education Lack of these programs in Sub-Saharan African is likely the reason why HIV/AIDS is not declining in this areas Social Implications People with HIV/AIDS can suffer from stigmas and discrimination Women are more likely to contract HIV from sex with an infected partner than men. People who die from HIV/AIDS are often at an age where they are the most productive members of society – removing individuals from the work force and delaying economic growth, an creating orphans Social Implications Unemployment poverty cannot afford treatments Poverty increases the chances of contracting HIV/AIDS due to lack of education on safe sex and increased prostitution Neutrophils – attracted to chemical signals given off by wbc damaged by microbes. They migrate toward infected tissue and engulf the microbe and wbc This creates pus – which is fragments of proteins and dead wbc and the digested microbe. When tissue is damaged because of physical injury the body responds with localized inflammatory response: swelling, heat, redness, pain If pus is present too, its a sign that the second line of defense has been at work Fever – this is the body’s response to infection When chemicals released by wbc reach the hypothalamus relaying information that the body is fighting off an infection, the hypothalamus’ response is to raise body temperature to ~40°C These conditions make it harder for the invader to survive and reproduce Some believe taking meds to reduce fever may prolong infection But high temperatures can be dangerous to humans who’s cells can’t survive above 43°C