What are basic mechanisms of defense against disease? A. Parasites organisms that live and reproduce on or within other life forms while doing harm in the process, our environment teems with parasites B. Microbes - viruses, bacteria, fungi and protists C. The immune system has three major lines of defense 1. Nonspecific- repels/kills/neutralizes all threats regardless the nature of the invader 2. The first ine of defense consists of the nonspecific external barriers a) Anatomical structures and secretions b) Prevents most microbes from entering the body 3. The second line of defense consists of the nonspecific internal barriers a) White blood cells b) Inflammation [NONSPECIFIC EXTERNAL BARRIERS ©) Fever 4, The third line of defense is the specific immune response a a) Immune cells selectively destroy Pee ER DO toxin/microbe and “remember” the invader ¥v Il How do nonspecific defenses function? A. Skin and mucous membranes form external barriers to invasion 1. The skin and its secretions block entry and provide an inhospitable environment for microbial growth FHGURE 32:1 Level of defense ogo iestion a) Surface of skin consists of dry, dead cells > lacks water and nutrients for microbes to survive > bacteria/fungi that can survive re usually shed b) Secretions (sweat glands, sebaceous oil glands, and wax-secreting glands in ears) contain natural antibiotics > inhibits bacteria growth 2. Antimicrobial secretions, mucus, and ciliary action defend the mucous membranes against microbes G) Warm, moist mucous membranes are more hospitable to microbes than skin b) Mucus and tears secreted by membranes contain antibacterial enzymes called lysozymes that destroy bacterial cell walls ©). Mucus traps microbes in nose/mouth > cilia sweep mucus out > mucus is. sneezed/coughed out or ingested > many microbes are killed by acid or protein- digesting enzymes and the intestine is lined with good bacteria that secrete substances todestroy bacteria/fungi B. Nonspecific internal defenses combat disease 1. Phagoeytic cells and natural killer cells destroy invading microbes ‘a) Phagocytic cells (macrophages and neutrophils) that travel the bloodstream destroy microbes, dead cells and cellular debris by phagocytosis (1) Macrophages also present antigens to cells involved in the immune response b) Natural killer cells destroy the body’s own cells that have become infected (1) Natural killer cells are white blood cells, (2) They secrete enzymes that attack the cell and proteins that open holes in the cell's membrane fo kill the infected cell 2. The inflammatory response attracts phagocytes to infected/injured tissue and isolates the infected tissuea) The inflammatory response causes mucous membranes to become leaky and injured tissues to become warm, red and swollen (1) Attracts phagocytic cells- chemicals released by damaged cells/mast cells/microbes attract macrophages and neutrophils (2) Promotes blood clotting to isolate the site of injury leaky capillaries and injured cells release chemicals > blood clotting > blocks damaged blood vessels and seals the wound off from the outside world (prevents microbes from entering) (3) Causes pain that stimulates protective behavior - pain caused by swelling and chemicals released by damaged cells b) The inflammatory response is inifiated by damaged cells > damaged cells release substances that cause mast cells (connective tissue cells) to release histamine (1) Histamine relaxes smooth muscle around arterioles > increases capillary blood flow and permeability > watery fluid is driven out of capillaries into the region ‘around the wound > area becomes warm, red and swollen (2) Chemicals released by damaged cells/mast cells/microbes attract macrophages and neutrophils (they squeeze through leaky capillary walls) (3) Macrophages release cytokines, chemical messengers that allow cells to ‘communicate with each other (4) Cytokines supplement histamine, attract more white blood cells and facilitates cell movement through capillaries , ae @ Mast cote rose hatin, @ Watmine erases capt ‘ood fw and pert YA Tha illommatory resoone 3. Fevers combat large scale infections a) Macrophages release cytokines (1) Endogenous pyrogen ("self-produced fire-maker") travels bloodstream to the hypothalamus and raises the thermostat to increase body temperature (2) Other cytokines reduce concentration of iron in the blood b) Fever enhances the body's defenses and harms microbes (1) Increases phagocytic white blood cells’ activity (2) Immune cells multiply more rapidly (3) Bacteria reproduce more slowly and require more iron (4) Increases production of interferon (another cytokine produced by cells) which increases resistance to viral attackIl What are the key characteristics of the immune response? A. Lymphocytes - specialized white blood cells in the blood and lymph 1. Bcells- form in bone marrow, mature/differentiate in bone marrow 2. Tcells- form in bone marrow, mature/differentiate in thymus 3. Immune response produced by B and T cells consists. ofthe same steps - ‘@) Cells of immune system recognize invader b) Launch an attack )_Retain memory of the invader for future infections B. The immune system recognizes the invader 1. Foreign invaders exhibit characteristic antigens a) Antigens (“antibody response generating’) -large molecules such as proteins, polysaccharides and glycoproteins (1) On the surfaces of invading microbes/cancer cells (2) Incorporated in plasma membrane (viral antigens) (3) Exposed on plasma membrane of white blood cells that engulf them (viral or bacterial antigens) (4) Dissolved in blood or extracellular fluid (toxic chemicals) 225 Aad sree 2. Antibodies and T cell receptors recognize and bind to Antibodies are proteins composed of two foreign antigens pairs of peptide chains (ight chains and a) Antibodies and T cell receptors are large proteins _ heavy chains) arranged like the letter Y. that recognize and bind to specific antigens Constant regions on both cheins frm the b) Antibodies - produced by B cells ‘stem of the Y; variable regions on the two (1) Attached to B cells of free floating in blood ——_chains forma specif binding steot the plasma tendo each arm ofthe ¥.Diferent (2) Y shaped with two pairs of peptide chains-_ antibodies have cifferent variable regions, ‘one pair of identical heavy chains and one pair fing unique binding sites. of identical light chains (3) Two functional parts: “arms” and “stems” (4) Constant region - same in an antibodies of the same type, stem of the antibody (5) Variable region - different among individual antibodies, located at tips of arms of the antibody, forms highly specific binding sites for antigens with particular shape and electrical charge (6) Five classes of true antibodies distinguished by structural differences of the stem/constant region, stem determines the mechanism the antibody uses to act against invaders (0) Crculating anibodies bind to antigens ona microbe and Promote phapooytoss by a macrophage. {01 Abo oun othe sudace ot a cl eecogizes microbes bearing foreign angen tony NA 4) nln: santgen —* FIGURE 32:6 Some fonctions of antibodies©) Tcell receptors - produced by T cells (1) Found only on surfaces of T cells, not released in bloodstream (2) Consists of two peptide chains of about equal size 3) Ends of the peptide chains protrude from T cell and form highly specific binding sites for antigens (4) Unlike antibodies, they do not directly contribute to the destruction of invaders 3. The immune system can recognize and produce specific responses to millions of types of molecules ‘@) There are no genes for an entire antibody molecule. Instead, many genes are ‘encoded for a variety of antibody fragments and pieced together into antibodies. (1) B cells only retain a few random fragments > they can only produce one type of antibody b) The immune system does not design antibodies or T cell receptors expressly to bind invading antigens (1) The immune system randomly synthesizes millions of different antibodies and T cell receptors > antigens would bind to at least a few antibodies and receptors (2) Binding of antigen to antibody > triggers changes in B cell > destruction of microbe with that antigen ) The immune system distinguishes “selt” from “norrsel” (1) Major Histocompatibilify Complex (MHC) - proteins on surface of cells that are unique to each individual except twins (2) Your own MHC proteins are foreign to other people's cells (3) Immature immune cells are destroyed when they contact molecules they treat as antigens > immature cells are unlikely to encounter foreign antigens so they won't get destroyed > only immune cells that treat your own cells as antigens are likely to encounter antigens and get destroyed C. The immune system launches an attack 1. Helper T cells stimulate humoral and cel-mediated immunity a) Helper T cells have T cell receptors for microbial antigens presented on plasma membranes of macrophages (that enguifed the invaders) or on surfaces of infected cells b) T cell receptors bind an antigen > cytokines released to stimulate cell division and differentiation of B cells and cytotoxic T cells ) Very little immune response can occur without this chemical boost by helper T cells 2. Humoral immunity - produced by B cells and antibodies they secrete into bloodstream a) Bcells and circulating antibodies attack invaders before they can enter cells b) Clonal selection - antigen-antibody binding causes B cells to divide rapidly, resulting population consists of “clones” that have been selected to multiply by the antigen ) Daughter cells differentiate into memory B cells and plasma cells, d) Memory B cells - provide future immunity to a particular invader, do not release antibodies ) Plasma cells - mass produce the required antibody (1) Much larger than B cells and packed with rough endoplasmic reticulum that synthesizes antibodies (2) Antibodies are released into biodstream > can only defend against invaders in blood or extracellular fluid (viruses are safe from antibodies as long as they are in the cytoplasm of cells) ) Humoral immunity destroys foreign chemicals/microbes in several ways (1) Antibodies bind to foreign molecule and inactivate it (neutralization) (2) Antibodies coat the surface of invading cell > promotes phagocytosis (3) Each antibody binds to two microbes, causing them to clump (agglutination) > promotes phagocytosis (4) Antibodies may bind to antigens with variable regions while their stems attach to (blood-borne) proteins of the complement system > triggers series of reactions > attracts phagocytic white blood cells, promotes phagocytosis, and sometimes directly destroy invaders by opening holes in their plasma membrane 3. Celmediated immunity - produced by cytotoxic T cells@) Helper T cells release cytokines after binding to antigens to stimulate B and T cell division and differentiation > some T cells become cytotoxic T cells b) Cytotoxic T cells attack invaders that made their way into body cells by releasing proteins that creates holes in the infected cell's plasma membrane ) After infection is over, some helper T cells remain and functions as memory T cells to protect the body from future infection D. The immune system remembers past victories 1. Plasma cell and cytotoxic cells directly fight microbes but only live for a few days 2. Memory cells survive for many years 3. During next infection, memory cells recognize invaders > multiply rapidly to produce immune response by generating huge amounts of plasma cells and cytotoxic T cells, from memory cells > the body can fend off the attack much quicker The Body's Cellular Armory Mast Cells Connective tissue cells that release histamine ; important in the inflammatory response Neutrophils | White blood cells that engulf invading microbes Macrophages | White blood cells that engulf invading microbes and present antigens Natural Killer_| White blood cells that destroy infected or cancerous cells. Cells Bcells __| Lymphocytes that produce antibodies Plasma cells | Offspring of B cells that secrete antibodies into the bloodstream Memory B cells | Offspring of B cells that provide future immunity against invasion by the same antigen Tcells | Lymphocytes that regulate the immune response or kill certain types ofcells Cytotoxic T _] Offspring of T cells that destroy specific targeted cells, including cells foreign eukaryotic cells, infected body cells, or cancerous body cells Helper T cells _| Offspring of T cells that stimulate immune responses by both B cells and cytotoxic T cells MemoryT cells | Offspring of T cells that provide future immunity against invasion by the same antigen“Targets invaders outsive cls (ruses, bacteria fungl protits, toxin) FIGURE 32-11 A summary of humerel end cellsmedicted immune responses,IV. How does medical care augment the immune response? A. Antibiotics slow down microbial reproduction 1. Antibiotics - drugs that retard the growth and multiplication of many invaders but not viruses a) Don't usually destroy every single microbe, the nonspecific internal defenses and immune response finish the job b) Potent agents of natural selection; mutant microbes who are resistant to an antibiotic passes that gene on > antibiotics eventually become ineffective in treating diseases 2. Neuraminidase inhibitors - antiviral drugs that block the ability of newly formed viruses toescape host cells in which they replicate B. Vaccinations stimulate the development of memory cells 1. Vaccination - the injection of weakened or killed microbes to confer immunity 2. Weakened microbes do not cause disease but do bear antigens to cause an immune response CC. Health Watch 1. Fluis caused by viruses that invade the respiratory tract 2. Flu virus have an amazing ability to change > our memory T and B cells aren't immune to future outbreaks of flu @) Flu virus genes are made of RNA (lacks mechanisms that reduce mutations in DNA) > more mutations 3. Rarely, deadly flu diseases appear with entirely new antigens and structures that the human immune system has never encountered before a) These viruses come from birds and pigs b) Human and bird viruses can infect pigs > both human and bird viruses can meet in the same pig cell > new virus from that cell have a mix of genes from human and bird viruses, some hybrid viruses combining the worst genes from each > hybrid virus can move easily from pigs to humans because pigs live near humans 4. Samples of mutated flu virus is collected from throughout the world > three strains that are most likely fo spread are selected > a vaccine is developed > usually effective if the correct strains were selected 5. Neuraminidase inhibitors can help if you already caught the flu by interrupting the virus's life cycle ‘@) The viral enzyme neuraminidase is important to viruses because it allows new viruses to escape host cells, © Fiest exposure to pation Stimulates 8 cel to produce V. What happens when the immune system malfunctions? A. Allergies immune responses to antigens that are not harmful 1. Bcell recognizes antigen (ex: pollen) > B cell produces plasma cells > plasma cells produce “allergy antibodies” > stems of allergy antibodies attach to mast cells > mast cells are primed to respond to subsequent exposure to that antigen L 2. Binding of allergens stimulates release of FIGURE 32-13 Allergic oodtions histamines, initiating the inflammatory responseB. Autoimmune disease - immune response against the body's own molecules 1. Noknown cure 2. Replacement therapy can alleviate symptoms (ex: administering insulin to diabetics, blood transfusions to people with anemia) 3. Autoimmune response can be suppressed with drugs but it also makes you more vulnerable to everyday diseases C. Immune deficiencies result when the immune system can't defend against infection 1. Severe combined immune deficiency (SCID)-a disorder in which few or no immune cells, are formed due to a defective gene ‘@) Inaculture dish, bone marrow cells from the child with SCID is infected with a virus that carries a functional copy of the defective gene > virus inserted genetic material {including functional gene) into DNA of the bone marrow cells > modified bone marrow Cells are injected into bloodstream > cells return fo bone marrow, proliferate and stimulate the production of healthy immune cells 2. Acquired immune deficiency syndrome (AIDS) - caused by human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) a) The viruses infect and destroy helper T cells that stimulate cell-mediated and humoral immune responses b) AIDS victims become vulnerable to disease due to the decline of helper T cells ¢) First recognized in 1981, it most likely arose from viruses that have been infecting chimpanzees in Africa > virus mutated and jumped from chimps to humans between mid-1940s and early-1950s d) Partially effective treatments but no cures for AIDS (1) Opportunistic infections can be treated like with any patient (2) New drugs that target retroviruses can disable HIV and slow the progress of AIDS > improves duration of the patient's life (3) Some drugs block reverse transcriptase, some block a protease that allows viruses to assemble in cells > effective in increasing life expectancy but HIV can oreenriens mutate and become resistant | to drugs and the drugs have side effects (4) Best solution would be to develop a vaccine but there are challenges: HIV vaccine has to evoke a more effect immune response than actual virus, HIV has incredible mutation rate 3. HIV-1 and HIV-2 are retroviruses a) Retroviruses- viruses that have RNA as their genetic material (they reproduce by transcribing suas rewcoone“ bail RNAinto DNA> insertingDNA este wanscrotase info chromosomes of a host cell) b) Outer envelope taken from infected host cell's plasma FIGURE 32-14 HV a Hv, he vis tt cours ADS, coo on oer eral membrane Shrenin coat ond baer prowiscopedles ich conten ¢) Twoprotein layers; innermost trite gone acencl st iv onde ety eres ton protein layer encloses Viral RNA ei ee ee ec ectne and enzyme called reverse potential torgets for AIDS voccines. 0b} The red specks in this col transcriptase ) Viruses outer envelope binds with miclomrorh, Fi os emaping hom he plasma membrane of T cell > bloc T cel nd ocauting on vey envelope ol plasma mem virus enters cell >reverse ‘re freer) fon He isced Fc transcriptase catalyzes the transcription of the virus’s RNA genome into DNA (process is called reverse transcription because it reverses the normal process ofe) f) DNA to RNA transcription) > resulting DNA is inserted into the T cell's genome > T cell starts making more viruses Patient fights off the infection at first > patients generally feel well and enough helper T cells still remain (can last for a few years) > helper T cell levels begin to drop > patient has AIDS > HIV levels skyrocket, helper T cell levels drop further > patient falls victim to other infections Transmitted by bodily fluids Cancer- disease in which the body destroys itself, characterized by the unchecked growth of malignant tumor cells, failure of the mechanisms that control the growth of the body's own cells a) b) d) e) Tumor - population of cells that has escaped normal regulatory processes and grows at an abnormal rate (1) Benign tumor (polyp) - cells remain confined to one area (2) Malignant tumor - cells grow uncontrollably and spread to other areas, it uses the body's energy and nutrients to grow and squeezes out nearby vital organs Natural killer cells and cytotoxic T cells screen the body for cancerous cells and destroy almost all of them before the proliferate and spread Cancerous cells are your own “self” cells but have new and slightly different proteins on their surfaces (due to the process that makes the cell cancerous) > gytotoxieT cells recognize these new proteins os “non-selt” antigens and destroy em However, the immune system can't destroy all cancerous cells and the tumor grows and spreads (1) Some cancerous cells evade detection because their surfaces don't have new proteins (2) Some tumors develop cells that are resistant to immune attack (3) Some cancers suppress the immune system (4) Some cancers grow too fast for the immune response to keep up ‘Three main forms of cancer treatment (1) Surgery (a) First step in treatment of many cancers (b) Can't remove very small patches of cancer cells that extend from main jumor (c) Can't treat cancer that has spread throughout the body (2) Radiation (a) Can destroy even microscopic clusters of cancer cells (b) Can't treat widespread cancers because that would damage a lot of healthy issues as well (3) Chemotherapy - drug treatment (@) Used to supplement surgery and/or radiation to treat cancers that can't be treated with surgery/radiation (b) Chemotherapy attacks dividing cells, selectively killing cancer cells > some healthy dividing cells also get killed in process