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Defense Against Disease
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Defense Against Disease

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  • 1. What causes disease? Defense • Microbes, microscopic organisms (including Against viruses, bacteria, fungi, and protists), are often Disease harmless but can sometimes be parasitic. – Parasites are living organisms on or within a host organism that causes harm in the process. Chapter 36 – Disease-causing microbes are called pathogens. Mechanisms of Mechanisms of Defense Defense • Vertebrates have three lines of defense against • First the pathogen must cross pathogens: nonspecific external barriers (skin, hair, tears, saliva). – Nonspecific external barriers. • If successful, it faces • Skin, hair, cilia, and secretions (tears, saliva, and mucus). nonspecific internal barriers – Nonspecific internal defenses. that make us feel sick (fever, • White blood cells that engulf or destroy all foreign coughing, sore, inflammation). particles. • The final line of defense is the – Specific internal defenses, the Immune Response. specific immune response in which special immune cells kill • Special white blood cells, or immune cells selectively and remember pathogens for destroy invaders and remember them for future attacks. future infections.
  • 2. Nonspecific External Defense Nonspecific External Defense • Animals have two surfaces which are exposed • Animals have two surfaces which are exposed to pathogens: skin and mucus membranes. to pathogens: skin and mucus membranes. – Skin is composed of several – Within the layers of skin are layers of thick cells, the pores which secrete fluids exterior of which is covered (sweat on the skin, wax in with a layer of dead cells. the ear) containing natural – Few pathogens penetrate the antibiotics that inhibit layer of dead skin before it is pathogens. sloughed off. http://www.eyeofscience.com/eos2/index2.html http://www.eyeofscience.com/eos2/index2.html Nonspecific External Defense Nonspecific External Defense • Animals have two surfaces which are exposed • Animals have two surfaces which are exposed to pathogens: skin and mucus membranes. to pathogens: skin and mucus membranes. – Mucus membranes surround the – Mucus membranes also eyes, and line the digestive and physically trap microbes and respiratory tracts of all mammals. foreign objects entering the – These are much more hospitable body in the mucus and cilia to pathogens. (protein filament-like hairs) – However tears and mucus contain that line the membranes. antibacterial enzymes called – If microbes are swallowed, lysozymes that destroy bacterial they are met with extreme acidity and digestive enzymes cell walls. in the digestive tract.
  • 3. Nonspecific Internal Defenses Nonspecific Internal Defenses • Once past external barriers (skin and mucus • The inflammatory response sends specialized membranes), pathogens encounter internal phagocytes. defenses: – Phagocytes consume infecting particles that penetrate external defenses. – An inflammatory response is triggered, bringing – Phagocytes make up 50-70% of white blood cells in the body. white blood cells to the scene. – Macrophages, specialized phagocytes, – Phagocytes, a type of white blood consume dead or dying cells to cell (a leukocyte), attack and destroy prevent the cytosol from leaking and all foreign particles. possibly infecting nearby cells. – If an infection occurs, a fever brings – Macrophages also act in the specific elevated temperatures which slow immune response. microbial reproduction. Macrophage consuming infecting bacteria. http://www.eyeofscience.com/eos2/index2.html Nonspecific Internal Defenses Nonspecific Internal Defenses The inflammatory response causes injured tissues to become The inflammatory response causes injured tissues to become warm, red, swollen, and painful. warm, red, swollen, and painful. Mast cells release Tearing of the histamine and epidermal (skin) respond to allergic tissue (1) causes reactions (3). wounded cells to Histamine makes release chemicals capillary walls that stimulate mast leaky and relaxes cells (2). the smooth muscles lining blood vessels (4).
  • 4. Nonspecific Internal Defenses Nonspecific Internal Defenses The inflammatory response causes injured tissues to become warm, red, swollen, and painful. Phagocytes attacking invading particles. E. coli cells being consumed and destroyed. A nematode under attack. With capillary walls relaxed and leaky, phagocytes can easily squeeze through walls and reach the site of infection (5). http://www.eyeofscience.com/eos2/index2.html Nonspecific Internal Defenses Nonspecific Internal Defenses • At the site of infection, an inflammatory response is felt: • At the site of infection an inflammatory response – Painful, swollen tissues as phagocytes rush to the scene. is felt. – Increased fluid production to remove any remaining • If this does not kill the pathogen and a full scale external pathogens. attack is launched, the body elevates its body – Pain caused by swelling and chemicals released by temperatures causing a fever. injured tissues to warn the injured organisms. – Increased fat metabolism. – Constriction of the blood vessels. – Conservation of heat through shivering. • This enhances leukocyte (white blood cell) reproduction and slows down microbial cell division. Normal lung cells Lung cells infected with Streptococcus pneumoniae
  • 5. Influenza Virus Activates the Non- Specific Immune Response How the • Influenza is an RNA virus that enters the Influenza Virus body through the nasal cavity. Attacks • Causes "flu-like symptoms": The virus particle binds to – Chills, fever, sore throat, receptor proteins on the surface muscle aches, coughing, of the cell (1) and enters the weakness. cell by endocytosis forming a vacuole (2). – Transmitted from person to person through the air. The viral membrane fuses with the vacuole membrane (3), releasing viral components into the cytoplasm (4). Nonspecific Defenses • External Barriers: How the – Layers of dead skin cells present an almost impregnable barrier. Influenza Virus – Mucus membranes trap and destroy foreign particles. Attacks • Internal Barriers: – Special leukocytes (white blood cells) called phagocytes engulf and break down foreign particles that get inside. The viral RNA genome – An inflammatory response calls phagocytes to the scene of migrates into the nucleus and infection, triggered by mast cells releasing histamine. is transcribed into mRNA (5). • Histamine relaxes capillary blood vessel walls to allow access to The viral mRNA is replicated in the nucleus and exported to the ER phagocytes traveling with blood. to make viral proteins (6). – If all this fails, a fever is induced with elevated body temperatures to retard pathogen growth. Viral coat proteins are exported to the plasma membrane and the viral mRNA leaves the cell by exocytosis creating a new virus (7).
  • 6. Specific Immune Response Specific Immune Response • Two types of leukocytes are important: • When the nonspecific response (exterior – B cells are white blood cells that produce antibodies. barriers, phagocytes, inflammatory response, and fever) • Plasma cells are B cells which secrete antibodies. fail, the body mounts a highly specific and • Memory B cells provide immunity against future coordinated immune response. infections. – A host of specialized white blood cells excrete – T cells are white blood cells that regulate the a variety of chemicals and immune response. communicate in complex ways. • Cytotoxic T cells destroy foreign eukaryotic and cancerous cells. • Helper T cells stimulate the immune response. • Memory T cells which provide future immunity. Specific Immune Response Recognizing the Invader • Both B cells and T cells follow the same • Immune cells recognize molecules specific fundamental steps in the immune system: to the invading microbe called antigens. – They respond to the immune system alarm, – Antigens generally are large complex recognizing the invaders. molecules like proteins, – They launch an attack (Plasma polysaccharides, and cells and Cytotoxic T cells). glycoproteins located on – They remember the invader for the surface of the cell. future infections (Memory B – Antibody proteins are cells and Memory T cells). produced by B cells to recognize pathogens. http://www.eyeofscience.com/eos2/index2.html
  • 7. Recognizing the Invader Recognizing the Invader • Influenza virus has • Antibodies are Y-shaped proteins with a two main antigens: variable region at one end. – Hemagglutinin • The variable region is altered (the H protein) between different antibodies – Neuraminidase (the N protein) to recognize and bind to different antigens. • Influenza virus • Binding of an antibody to a strains are named pathogen’s antigen causes the by their H and N B cell to differentiate into proteins. plasma cells and Memory B (H1N1, H5N1, etc.) cells. http://www.cdc.gov/h1n1flu/images.htm Recognizing the Invader Recognizing the Invader • Antibodies are made from a patchwork of genes, creating the variable region from a • Plasma cells secrete additional pool of shorter gene antibodies that bind and can sequences. modify antigens. • This allows the body to • Some antibodies make antigens produce an “army” of B more appealing to phagocytes. cells, each with its own • Some prevent the microbes from unique antibody, adhering to host cells. • Some block viral entry into the without coding for each cell. one individually. • Some deactivate toxins.
  • 8. The B cell Attack The B cell Attack • Triggered by the • This cloned population Helper T cells, of daughter cells B cells bearing many differentiate into two different antibodies types of B cells: appear on the scene – Memory B cells and Plasma cells. of infection. • Memory B cells • Only the B cell persist to preserve the carrying the antibody antibody specific to recognizing the this invading microbe antigen present will for future infections. reproduce a clonal population. B cell before infection The B cell Attack • This cloned population of daughter cells The Plasma Cell differentiate into two types of B cells: – Memory B cells and B cell differentiated into a Plasma cells. Plasma cell after infection • Plasma cells are packed with rough endoplasmic reticulum to synthesize large Endoplasmic Reticulum quantities of antibody to deactivate the microbe.
  • 9. B Cells Fighting an Infection Recognizing the Invader by Clonal Selection • T cells produce T cell receptor proteins that also recognize and help destroy pathogens. • T cell receptor proteins remain attached to the surface of T cells. • They alter the activity of the attached T cell rather than alter the antigen directly. B cells T cells The T cell Attack • Helper T cells respond to antigens on the surface of macrophages (from consumed pathogens), causing T cell differentiation into Cytotoxic T cells and Memory T cells. – Cytotoxic T cells are covered with T cell receptors that recognize infected cells. – They bind to the infected cell and release proteins to the interior of the cell causing it to break down. – Memory T cells develop when the infection is over to remember the type of attack for this particular infection.
  • 10. B cells T cells B cells T cells B cells T cells B cells T cells
  • 11. Medical Care Supplements the Medical Care Supplements the Immune Response Immune Response • Vaccines introduce the body to pathogens • Vaccines, a “short-cut” to immunity, can be made in to make memory B cells and memory T several different ways: cells before an infection. – Disease-causing organisms are killed or weakened so they cannot cause disease but still retain surface antigens. The first exposure to the – Specific antigenic molecules are purified from the killed antigen causes a disease-causing organism. small immune response – Harmless organisms are genetically modified to encode allowing the immune for a specific antigen without causing disease. response to the second exposure to come on – A related pathogen that causes no (or very mild) much faster and stronger symptoms is used to stimulate an immune response to a than without the vaccine. common antigen. The First Vaccine Medical Care Supplements the • Smallpox was once on of the deadliest killers of the human race. Immune Response – The virus killed 30% of infected persons. Exposure to the antigen of a disease-causing microbe • The first vaccines against the disease were developed causes memory cells to remember the antibodies specific in 1796 when an English surgeon recognized the for that pathogen. similarities between smallpox and cowpox (a severe – Now many diseases are controlled with but not as deadly disease). vaccinations: polio, typhoid fever, mumps, – He inoculated an 8 year old boy with bacteria measles. possessing the cowpox virus. – Smallpox has been completely eradicated – Months later, he inoculated the boy with the since 1980 due to vaccinations by the smallpox virus and he survived the infection. World Health Organization. – Soon people all over Europe were being • Only two laboratories in the world legally keep vaccinated against smallpox using the stocks of smallpox, in case “bioterrorists” have a cowpox virus. store and use it as an attack and more vaccines are needed. The Smallpox Virus
  • 12. Medical Care Supplements the Immune System Malfunctions Immune Response Allergies are an immune • Just like a fever, antibiotics slow down microbial response to harmless reproduction. substances. – An antibiotic is a chemical drug that targets specific cellular – B cells recognize an functions in invading Prokaryotes and Eukaryotic pathogens antigen on the allergen (fungi and protists). surface, launching an – Antibiotics are not capable of destroying the microbe immune response. – They retarding its progress so that the body’s immune – Antibodies produced bind response can launch its attack. to nearby mast cells which – Mutants can spontaneously arise that are release histamine whenever immune to a specific antibiotic and spread the allergen antigen binds that mutation to future populations. its antibodies. Immune System Malfunctions Immune System Malfunctions •Immune Deficiency Diseases disable the immune system. • Autoimmune Disease occurs when the – AIDS (acquired immune deficiency body initiates an immune response against a syndrome) is caused by HIV, the particular type of normal body cell. human immunodeficiency virus, which – After a pathogen infection, B cells mistake infects and destroys Helper T cells. body cells for pathogens and create antibodies • Without Helper T cells, B cells and against them. Cytotoxic T cells are not activated to • Multiple sclerosis occurs when immune cells attack combat diseases. the insulating fatty sheath coating neurons of the • AIDS patients often die from common brain and spinal cord. diseases (like pneumonia) that healthy • Rheumatoid arthritis occurs when the immune people fight off every day. system attacks cartilage of the joints.
  • 13. How the HIV Virus Attacks How the HIV Virus Attacks How the HIV Virus Attacks HIV, a Retrovirus • HIV is a retrovirus, an RNA virus that reverse transcribes its genome into DNA to incorporate it into its host genome. – Retroviruses are the only type of virus that can incorporate its genome into a host genome. – Once incorporated, the host cell becomes and remains a viral manufacturing plant, producing thousands of viral particles in an average Eukaryotic cell’s lifespan.
  • 14. Immune System Malfunctions Immune System Malfunctions Cancer results cells fail to recognize signals to stop dividing and avoid • We are exposed to apoptosis (programmed cell death). carcinogens (cancer-causing Since most cancers are not caused by agents) every day. an external pathogen, cancer is hard to target by the immune system. • The most common carcinogens are Cancerous cells grow, unchecked, and gamma rays from form malignant tumors that the sun and eventually spread throughout the body. naturally produced Benign tumors remain in one area and do carcinogens in our not spread. food. Skin cancer, one of the most common forms of cancer, begins with a melanoma. Immune System Malfunctions • Cancer, unlike other forms of immune system malfunctions, can be treated and cured. – Surgery is the first step to remove the cancerous tumors. – Radiation bombards the tumor cells with high energy electrons to disrupt their DNA. – Chemotherapy drugs attack the machinery of cell division, but unfortunately also kills some healthy cells too (in particular hair follicles and the lining of the intestines). • The best medicine is preventative: refrain from engaging in activities that expose you to carcinogens (quit smoking, stop sunbathing, eat lots of vegetables and less fat, exercise, etc.)