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Bio 103 Exam Study Notes.docx

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Queen's University
BIOL 103
Virginia K Walker

Bio 103 Exam Study Notes Virginia Walker’s lab projects on the genetic mechanisms of resistance - Resistance to chemicals: chemo causes birth defects, developed system so that we don’t need to test on mammals (flies) - Resistance to environmental stresses: freeze and freeze-thaw resistance in plants, invertebrates and microbes (hydrate control) - Effects of pollutants on organisms (nanoparticles) Nutrition and Digestion Autotrophs: harvest light or chemical energy Heterotrophs: eat other organisms Fungi can be parasitic or predatory - Can be parasites, get nutrients from living animals (athlete’s foot, dactylella dreschsleri, arthrobotrys dactyloides) Intracellular Digestion - Protozoa - Phagocytosis (85 different proteins involved, cell eating) - Endocytosis (cell drinking) Extracellular digestion - Digested food products are phagocytosed directly into the cells that line the gastrovascular cavity- further digested intracellularly - Wastes are excrete out of the mouth - One opening for entry and exit of food - Cellulose  cellulase via microorganisms - Caecum: developed during the evolution of plant eating animals, beginning of large intestine - Rabbits eat their own poop so that the small intestine can have another chance at digesting food - Ruminant: mammal that chews cud regurgitated from its rumen - Digestive tract- mouth, esophagus, forestomach (rumen, reticulum, omasum), abomasums, intestines - Steven Chu- use termites to convert cellulose into ethanol= green energy - Digestion= complex organic molecules  simpler molecules digestion Digestive enzymes 1. Oral cavity: teeth, salivary glands - Purpose of saliva is to moisten and digest food, defense functions, produce 1000mL per day, contains amylase - Starch (polysaccharide)----(amylase, hydrolysis reaction)- maltose (2 glucose units) 2. The stomach - When food enters our stomach gastric juice (HCl, pepsin) is secreted - Pepsin is a protease (member of an enzyme family that is important for the hydrolysis of proteins) - How does the stomach lining avoid getting hydrolyzed by pepsin and damaged by HCl? a) Gastric glands in the chief cells lining the stomach produce pepsin in an inactive form, pepsinogen (inactive enzymes are called zymogens and the pepsin zymogen= pepsinogen) b) Goblet cells that line the stomach produce a viscous mucous layer with a pH ~6 c) The parietal cells that produce the HCl don’t accumulate the acid. It forms in the stomach after secretion of H+ and Cl- ions. (Note: the parietal cells are signaled to produce HCl by a peptide hormone). d) Cells lining the stomach have particularly resistant membranes - Ulcers are caused by bacteria (helicobacter pylori), can be treated with antibiotics, gastin stimulated the growth of the bacteria - Crop: a pouch like expanded part of the oesophagus of birds, in which food is stored or partially digested before passing on to the gizzard - Gizzard: contains tiny pebbles that help pulverize food - Stomach: secretes HCl and pepsinogen 3. Small intestine - The contents of the stomach (=acid chyme) then pass on to the small intestine where there is a large number of digestive enzymes produced by a) Intestinal glands (maltase: takes maltose and hydrolyzes it to glucose, proteases) b) Pancreas (restores pH to approximately neutral pH 7, proteases) c) Liver (digestion of fats) - Proteases o Endoproteases: hydrolysis of peptide bonds within a polypeptide (e.g. pepsin, trypsin, enterokinase, chymotrypsin, elastase) o Exoproteases: hydrolysis of terminal peptide bonds (e.g. aminopeptidase, dipeptidase, carboxypeptidase) - Digestion in the small intestine o Intestinal glands: maltase + proteases  enterokinase, aminopeptidase, dipeptidase o Pancreas: proteases  carboxylpeptidase, trypsin, chymotrypsin, elastase  Pancreatic amylase (starch  maltose)  Lipase (fats  fatty acids + monoglycerides)  Nuclease (nucleic acids  nucleotides)  Sodium bicarbonate o Liver: bile (large fat droplets  smaller ones) - Digestion in insects has no pepsin o Instead, salivary glands and active proteases eliminated with feces - Absorption of the digested products, vitamins, minerals and water occurs in the small intestine - It’s assisted by the huge surface area of the small intestine contributed by the villi (contains lacteals and capillaries) and microvilli Excretion and Ion Transport - After digestion, individual amino acids are absorbed by cells lining the small intestine and then enter the blood - Liver (urea cycle): NH3 + carbon dioxide + H20  urea - Sharks change their blood volume depending n the saltiness of the water they’re swimming in Isotonic: solute concentrations are equal inside and out Hypotonic solution: solute concentration is lower outside the cell Hypertonic solution: solute concentration is higher outside the cell - Salt water (bony fish) are hypotonic; in danger of dehydrating with water lost across the gills o Therefore, they have to drink lots of water o Excreted ammonia is diluted with a minimum amount of water = concentrated urine o Excess salt is transported out of the body by specialized cells in the gills - Fresh water fish are hypertonic; in danger of being water logged o Produce large amounts of dilute urine o Specialized gill epithelial cells transport Na+ and Cl- from water into fish’s capillaries Relative salt concentration in various animals and the ionic concentration (Cl-) of seawater Department of the environment- Guideline for the Release of Ammonia Dissolved in Water Found in Wastewater Effluents Human disease - Liver cirrhosis caused by alcoholism, infectious disease (e.g. hepatitis) or fatty liver disease - One of the leading causes of death in the middle years in western countries - One consequence is that the damaged liver cannot efficiently carry out the urea cycle In bird, reptiles and insects… Why is uric acid the nitrogenous waste of birds? Uric acid is stored in the allantois and is left behind at hatching - Guano: birds excrete uric acid and this is found in droppings with digestive waste. It was important in earlier years as a fertilizer. Interesting Adaptations - Lungfish adaptation to high ammonia concentrations - Salmon can make drastic change from salt to fresh water. The gill epithelial cells are able to transport both Na+ and Cl- against the concentration gradient (using ATP) - American eel is found in fresh and sea waters along East coast/Lake Ontario To get rid of nitrogenous wastes, organisms need excretory organs 1. Filtration: acts like a filter to remove water and small solutes from body fluid or blood while leaving behind blood cells, proteins and other large solutes 2. Reabsorption: useful material in the filtrate recaptured and returned to blood 3. Secretion: may put additional solutes into the filtrate (can aid in the elimination of toxins) - Vertebrates have a kidney containing specialized tubules with cells that actively transport ions for salt and water homeostasis and nitrogenous waste elimination - The rest of the urinary system consists of the ureters, urinary bladder and urethra The nephron: functional unit of the kidney in higher vertebrates - Capillary network in the renal corpuscle (Bowman’s capsule + glomerulus) forms filtrate - Long tubule that performs secretion and Reabsorption - A collecting duct that empties into the central cavity of the kidney o Outer renal cortex and inner renal medulla o In the medulla, urine becomes concentrated by the re-absorption of water back into the blood o Bowmans, proximal convoluted tubule, the loop of Henle, distal convoluted tubule, collecting duct o Water leaves descending loop of Henle, salts leave ascending loop of Henle - Water moves very quickly across the nephron membranes - Discovered rapid movement of water was aided by “water pores” or aquaporins o This discovery explained why water can diffuse through kidney membranes more quickly than theoretically possible o Aquaporin family members can also transport other small molecules (e.g. urea) o Protein structure forms loops, which form opening about the same width as the small molecules that will be transported - At least 13 members of the aquaporin gene family have been cloned in humans. The genes are expressed in different parts of the kidney. For example, aquaporin 1 is expressed in the proximal part of the tubule and aquaporins 2 and 3 are expressed in the collecting ducts. - In the kidney, active transport of Na+ and other substances is needed. Active transport is also required in the sale-secreting cells in fish gills. Bio 102 review: Passive transport: water, ethanol, gasses Facilitated diffusion: a channel in the membrane allows transport across the membrane into the cell, or out of the cell (e.g. after digestion of carbohydrates, fructose enters the cells lining the small intestine using facilitated diffusion) Secondary active transport: after digestion, Na+ and glucose enter the cells lining the small intestine Transporters: Na+/K+ ATPase (sodium potassium pump) - 3 Na+ out for ever 2K+ in the cell= electrical gradient - Sets up Na+ gradient used for 2 transport (co-transport) - Keeping Na+ tends to lower osmotic potential cells (makes cell slightly less hypertonic to the medium that it’s sitting in then it normally would be) - Uses 30% ATP - A tetramer (4 polypeptides) encoded by 2 different genes Examples of other pumps: P-glycoprotein pump: these are drug efflux transporters, which are important for the transport of hydrophobic drugs out of the cell; have ATP binding site Bile sale export pump (BSEP): this ATP-dependent bile salt transporter functions in the liver. Mutations in this gene can lead to cholestasis characterized by poor fat metabolism, dark urine, severe itching, jaundice, liver failure and death (some are saved with liver transplant) Cystic fibrosis transmembrane conductance regulator protein (or CFTR permease): this pump is a chloride transported found in lungs, sweat glands and some cells of the digestive tract. Recent publications show that it has two ATP binding sites and is an active transporter. About 4% of Canadians have a mutant CFTR gene. Movement and Muscle Control - Plants move using turgor pressure - Protists can move using cilia or flagella - Animal cells move using contractile proteins in microfilaments Exoskeleton: the "framework" of the creature is on the outside, like the lobster Endoskeleton: inside the creature, so the soft parts are outside, like the bear or man Major proteins: - Actin - Myosin Minor proteins: - a-actinin - Capping protein - Tropomyosin - Troponin complex - Other proteins All of these proteins work together to for skeletal muscles Muscle contraction - Signal to contract by Ca++ o Smooth muscle  Ca++ comes across plasma membrane o Skeletal muscle  Ca++ endoplasmic reticulum (sarcoplasmic reticulum) - Ca++ binds to tryponin complex and uncovers the binding site on actin where myosin is going to sit - Myosin binds to actin and drops a phosphate group - ADP is released, myosin is still attached o 5-10 times per second - A muscle is a grouping of cells (muscle fibres) bound together by connective tissue - Tendons link bones to skeletal muscle - Skeletal muscle fibers increase in size during growth but no new fibers are formed - Meat must be hung to be tender. Freezing meat right after slaughter allows ice crystals to rip open the sarcoplasmic reticulum, allowing muscles to contract when they thaw. - Looking at a myofibril o A band: dark band  H zone/band: space between the 2 sets of thin filaments (the M line is in the center) o Z line/Z disk: think filaments are anchored to network of proteins (the region between 2 successive Z lines make a sarcomere) o I band: contains portions of thin filaments that do not overlap thick filaments o Sarcomeres shorten as thin filaments slide past stationary thick filaments o Myosin molecules attach to thin filaments and force them toward the center of the sarcomere o Formation of cross-bridges repeats the motion as long as the stimulation to contract continues Strength training: contracting muscles against resistance (e.g. weight training) increases the number of myofilaments in each muscle fiber Endurance training: increases the number of blood vessels in a muscle and increases in the number of mitochondria in the muscle fibers, thus increasing your capability to sustain muscle contraction over a long period (e.g. running) Disuse atrophy: a decrease in the number of myofilaments in each muscle fiber Three major types of muscle fibers 1. Slow oxidative fibers- contain a types of myosin with relatively low ATPase activity but with numerous mitochondria- for prolonged, regular activity (sometime called red muscles) 2. Fast-oxidative fibers- contain a type of myosin with high ATPase activity and numerous mitochondria- for rapid actions 3. Fast-glycolytic fibers- contain a myosin with high ATPase activity but there are few mitochondria, and relatively little available myoglobin (the resulting pale colour is responsible for their other name, while muscles) – for rapid, intense actions but the muscle fatigues quickly sarcolemma: plasma membrane of muscle cell sarcoplasmic reticulum: endoplasmic reticulum of muscle cell sarcoplasm: cytoplasm of muscle cells myoblasts: immature muscle cells Neural Transmission and Nerve Control The nervous system consists of the brain, spinal chord, sense organs and the nerves. Neurons: send and receive electrical and chemical signals to and from other neurons throughout the body Glia: cells that produce the connective tissue and organize the zones around the neurons, producing myelin for certain nerves Nerve tract: bundle of axons Ganglion: collection of neuron cell bodies Myelin sheath: formed by glial cells and acts as an ‘insulating material’ Sensory neuron: gets information from the outside world Motor neuron: sends signals away from sensory neurons for a response Interneuron: make interconnections with other neurons Sensory transduction: process by which incoming stimuli are converted into neural signals Sensory receptor: a neuron or specialized epithelial cells that recognizes an internal or environmental stimulus and initiates signal transduction by creating graded potentials in the same cell or adjacent cells Sodium channel- sodium floods cell, inside becomes more positive than outside, potassium ion (also positive) leaves cell to make inside cell negative - Hyperpolarization happens because potassium gates are slow to close How fast does the signal go? Depends on: - Axon diameter: broader axons provide less resistance and action potential moves faster - Myelination: myelinated neurons are faster then unmyelinated (note that a myelin sheath is not continuous; there are gaps at the nodes of Ranvier and the action potential “jumps” or flows through cytosol to next node) Synapses - Junction where neuron meets another neuron or muscle cell, etc. - There is a presynaptic cell (sends signal), synaptic cleft and postsynaptic cell (receives signal) - 2 types: electrical (charge flows through gap junctions from cell to cell), chemical (neurotransmitter acts as signal from presynaptic to postsynaptic cell) 5 classes of neurotransmitters: 1. Acetylcholine - One of most widespread neurotransmitters - Released at neuromuscular junctions - Excitatory in brain and skeletal muscles but inhibitory in cardiac muscles 2. Biogenic amines - Abnormally high or low levels associated with a variety of disorders (schizophrenia, Parkinson disease and depression) 3. Amino acids - Glutamate is the most widespread excitatory neurotransmitter - GABA (gamma aminobutyric acid) most common inhibitory neurotransmitter in the brain 4. Neuropeptides - Often called neuromodulators – can alter response of postsynaptic neuron to other neurotransmitters e.g. opiate peptides, oxytocin 5. Gaseous neurotransmitters - Produced locally as needed and are short acting, influencing cells after diffusion across the membranes - Several drugs for male sexual dysfunction (e.g. Viagra) enhance/mimic the action of NO by relaxing the smooth muscles in the penis and allowing increased blood flow - Function of CO uncertain 1. Na+/K+ ATPase restores ion balance 2. After repolarization, Ca++ goes out of the cells, using the Na+ gradient 3. Acetylcholine  acetate + choline Medical Applications - Insecticides: organophosphates inhibit insect acetylcholinesterase; DDT and pyrethroids act on the v.g. Na+ channel - Myasthenia gravis reduces the number of functional acetylcholine receptors - In multiple sclerosis the myelin is destroyed - Other poisons such as bungarotoxin inhibits the acetylcholine receptor and tetrodotoxin binds to the voltage-sensitive Na+ channel, as do local anaesthetics - The “hot pepper receptor” is actually a heat receptor Representative nervous system - Except for sponges, all animals have a nervous system - Nerve net: is a simple nervous system found in cnidarians (jellyfish, hydras, anemones). The neurons connect to each other in a network. - Echinoderms: nerve ring around mouth connected to larger radial nerves extending to arms - Planaria: nerve cords extend length of animal connected by transverse nerves and a collection of neurons in head form a ganglia that performs and integration function - Annelids: these have more neurons and ventral nerve cords that have ganglia in each segment - Simple mollusks: these are similar to annelids with a pair of anterior ganglia and paired nerve cords - Cephalization: increasingly complex brain in the head o Flies have a centralized brain with several subdivisions with separate functions, mollusks have brains with well-developed subdivisions Origins of a nervous system 1. More neurons 2. Concentration of neurons in specialized structures (ganglia/nuclei, simple “brains”, thick nerves and nerve tracts) 3. Specialization of function a. Afferent neurons carry signals toward a brain b. Efferent neurons carry signals away from the brain 4. Complex synaptic contacts a. Many synapses from a single neuron b. Many interneurons (neurons connecting neurons) - Many simple animals have centralized neural control but not in the head - “Advanced” animals show the evolutionary trend toward cephalization - Each region of the vertebrate brain is specialized for processing a specific type of information, such as sensory input (sight, smell, hearing) SPAUN (sematic pointer architecture uniform network): an artificial brain with 2.5 million neurons that do several tasks including number puzzles. It is unlike the computer Watson that is dedicated to information retrieval. Internal Transport and Circulation Open circulatory system: hemolymph (interstitial fluid) flows through the body and is not confined to special vessels Closed circulatory system: blood flows throughout an animal entirely within a series of vessels and is kept separate from the interstitial fluid Arteries: blood vessel that carried blood away from the heart Veins: blood vessels that return blood to heart Capillaries: a thin-walled vessel that is the site of gas and nutrient exchange between the blood and interstitial fluid Lymphatic system: a system of vessels along with a group of organs and tissues where most leukocytes reside. The lymphatic vessels collect excess interstitial fluid and return it to the blood. Cardiovascular System- Major Functions - Transport of gases between the environment and the tissues (oxygen to tissues, carbon dioxide from tissues) - Transport of nutrients and metabolic waste products between tissues - Defence- Immune system Blood components Blood Clotting 1. Injury ruptures a blood vessel 2. Platelets stick to each other and to collagen fibers, forming a plug. Blood loss is reduced. 3. Fibrin forms a meshwork that traps cells and platelets, forming a clot that seals the wound. Blood Clotting Cascade (more detail) 1. Injury  prostaglandin (hormone), sticky  platelet factor (positive feedback loop to prostaglandin with Calcium) 2. Platelet factor + calcium + other clotting factors convert prothrombin (zymogen) to thrombin (endoprotease) 3. Fibrinogen (inactive) uses thrombin to become fibrin (active) 4. Fibrin polymerizes with calcium to create fibrin cells 5. Red blood cells get caught in fibrin to make a mature clot 6. Aspirin inactivates the enzyme COX, with make prostaglandin Practical Applications - Genetics of clotting diseases- factor IX located on the X chromosome (Hemophilia B, royal family) - Warfarin- stops liver enzyme (rats bleed to death from the inside) Gas Transport and Respiratory Systems Chapter - Red blood cells contain hemoglobin and plasma membrane (with gylcoproteins including ABO and Rh glycoproteins) - No nucleus so it can fit more hemoglobin - Dimple for more surface area Hemoglobin: tetramer (2 beta groups, 2 alpha groups) and has 4 heme groups Spirometry: used to help diagnose and monitor chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis, etc. Measures the volume (forced vital capacity) and flow (force expiratory volume in 1 sec) of inhaled and exhaled air. - Mammal’s circulatory system is separated from the pulmonary and systemic circuits - The pulmonary circuit is exposed to high partial pressure of oxygen (PO2) at the lungs Air= 21% oxygen, 78% nitrogen, <1% carbon dioxide and other gases Atmospheric pressure: pressure on the body surfaces of animals measured in mmHg or kPa (1kPa=7.5mmHg) - It is the sum of the partial pressure (pressures exerted by each gas in air) in proportion to their amounts) - PO2= 0.21 * 760 mmHg (sea level) = 160 mmHg - Diffusion across cell membranes is driven by partial pressure gradients o In the lungs, oxygen diffuses across the membranes and is picked up by the hemoglobin. Any carbon dioxide is released because the partial pressure of carbon dioxide is lower. Dalton’s law: the total pressure is the sum of the partial pressures - In capillary beds, the partial pressure of oxygen is low and the O2 is released by the erythrocytes Gas exchange: oxygen and carbon dioxide cross membranes - Recall that carbon dioxide is released from the tissues during cellular respiration Sea level= 760 mmHg - Atmospheric pressure decreases at higher elevations Hb (hemoglobin) saturation vs. PO2 (partial oxygen pressure) - To increase red blood cells (hematocrit), it would take 2-3 weeks - Infants have hemoglobin that allows them to be fully saturated with oxygen with a lower hemoglobin count - Sickle cell anemia is but one example of a blood disease cause by a mutation. The ‘mutant’ hemoglobin aggregates at a low PO2, which damages the erythrocyte membrane. - The frequency of the mutated beta globin gene is very high in areas of Africa where malaria (caused by Plasmodium sp.) is endemic - Thalassemias: reduction in the synthesis of a of B globins o α thalassemia- most common in Asian populations o β thalassemia- most common in Mediterranean populations Anemia - Both of these and sickle cell anemia can result in anemia. Symptoms: fatigue, pale or cold skin, weakness, dizziness. - Too few red blood cells reduce the delivery of oxygen to tissues - Anemia can result from many causes: o Hemolytic anemia (fragile cells such as sickle cell anemia or reduced cell number as in the thlassemias) o Pernicious anemia (folic acid deficiency) o Iron deficiency o Malaria and other parasites that destroy red blood cells o Aplastic anemia (bone marrow destruction) o Blood loss Defence and Immunity - Killer T cells attack cancer cells, which is detected because of its foreign antigens Specific immunity: when a pathogen is detected, a series of processes will trigger specific antibodies that will be produced faster upon a second infection st nd Non-specific immunity: general 1 and 2 lines of defence (e.g. fever, inflammation, mucus) Humoral Response - Mediated by lymphocytes that mature in the bone marrow, called B cells - They mature to form plasma cells (or mature B cells) that synthesize and secrete antibodies o B cells  differentiate into plasma cells o Plasma cells  secrete antibodies  mature B cells - Antigen= antibody generating- normally a foreign protein, glycoprotein, polysaccharide, etc. - Y= antibody – proteins that bind antigen o Immunoglobulin protein family o Each composed of 4 polypeptides (2 long heavy chains, 2 short light chains) o Mammals have 5 classes - All B cells are different- when an antigen fist appears, only a few B cells (virgin B cells) can bind - Humoral response works after the detection of a foreign antigen by a B cell, but B cells don’t directly kill the pathogen - Because an antibody has two ‘arms’ and can bind two antigens, antibodies and antigens can clump together= agglutination After agglutination: 1. Phagocytes (macrophages) can easily engulf the clump 2. Natural killer cells (NK lymphocytes) destroy the cells marked with antibodies 3. There is activation of complement (a cascade reaction involving ~20 proteins that ‘builds’ a hole in the invader’s membrane) Opsonization: the process whereby the nonspecific immune system can link invading microbes to phagocytes, complement proteins, or natural killer (NK) cells How is the enormous diversity required actually generated? Answer: the light chain. Gene assembly, novel joints and hypermutation together produce a huge number of different immunoglobulin light chains- Summary 1. Gene assembly increases diversity - Coding regions for antigen binding sites are assembled to generated genes that can be transcribed - The enzymes for the assembly are expressed only in developing lymphocytes 2. Joining of cut domains is not always precise, resulting in different amino acid sequences at ‘novel joints’ 3. ‘Hypermutation’ is a result of point mutations (C to T) during DNA replication, which in turn changes amino acid sequence - Assembly of the heavy chain is even more complex with 500 V regions and two types of J regions (=joining and diversity regions) Cellular immune response - These cells, unlike the B cells, mature in the thymus and are therefore called T cells - Many of the cellular components in blood, including the T-lymphocytes, originate in the bone marrow - T cells have a T receptor o This is a dimer with an a- and b- polypeptide chain (variable and constant regions) o The constant region have a transmembrane domain T cell receptor assembly: recombination  transcription splicing translation  (α and β pair soon after biosynthesis to form the receptor) translation splicing transcription  recombination Major histocompatibility complex (MHC) - Cellular “identity tags” that are genetic markers of self - MHC I is found on most cells in the body (an exception is the erythrocytes) o Binding is stabilized by CD8 (on the killer T cells = cytotoxic T cells) - MHC II found only on antigen-presenting cells such as macrophages (or presentation cells), B cells and a few other immune system cells o Binding is stabilized by CD4 (on helper T cells) 4 functions of the helper T cells 1. The helper T cell binds to an APC (macrophage) a. Binding releases a chemical signal (peptide hormone cytokine= interleukin, IL) which stimulates mitotic division of the helper T cell (sometimes called the T4 cell for obvious reasons) 2. The helper T cell binds B cells bearing an antibody and a bound antigen a. When bound, interleukin is released which stimulates the B cells to divide and produce a clonal population of B cells resulting in more plasma B cells and the synthesis of specific antibodies 3. The helper T cell produced cytokines which stimulate killer T cells (cytotoxic T cells) to attack ‘infected’ cells a. Killer T cells attack cells with a specific antigen and MHC I with the interaction stabilized by CD8 b. They kill by releasing perforin (makes channels or perforations in membranes of cells) 4. The helper T cell binds to the killer T cells (cytotoxic T cells), produced cytokines (ILs) to produce a clonal population of killer T cells and memory killer T cells a. New research shows that platelets are also involved by binding bacteria and bringing them to killer T cells, promoting expansion of the population of killer T cells. Platelet hormones can also prolong the activation of the killer T cells in viral infections population of killer T cells (including some memory killer T cells with the same specificity after proliferation). What happens next? 1. A cytotoxic T cell binds to the surface of a virus-infected cell. 2. A helper T cell binds to a macrophage that has phagocytized the same type of virus. The helper T cell then proliferates and binds to cytotoxic T cells. The helper T cell secretes IL-2 and other cytokines that stimulate the helper T cells and cytotoxic T cells to divide. 3. Cytotoxic T cells bind to other virus-infected cells 4. Each cytotoxic T cell secreted perforin that inserts into the plasma membrane of a virus-infected cell and kills it 5. Cytotoxic T cell can then kill other virus-infected cells Perforins= pore forming proteins - Made by killer Ts and natural killer cells through the synthesis of cytokines. They polymerize in the presence of Ca++ to make transmembrane channels in infected cells. Immunological memory Immune tolerance - Body distinguishes between self and non-self components - Huge diversity of lymphocyte receptors also generates receptors binding to self - Mechanisms prevent an immune response to “self antigens” o Clonal deletion during early development- “self recognizing T cells” in the thymus are destroyed by apoptosis (=cell death) o Clonal inactivation outside of the thymus- potential self-reacting T cells become nonresponsive o B cells undergo similar processes o BUT sometimes these mechanisms can go wrong Autoimmune disease: the immune system attacks the body’s own tissue and cells - Multiple sclerosis- myelin attacked - Myasthenia gravis- acetylcholine receptors on skeletal muscle cells attacked - Rheumatoid arthritis- joints attacked - Type 1 diabetes mellitus- insulin-producing cells destroyed - Hashimoto’s disease- thyroid attacked - Treatment options? Treat symptoms or suppress the immune system (drugs like glucocorticoids that inhibit the production of cytokines). Very new treatment options could come from stem cell research. No functional B cells= no agglutination response = no antibodies= babies die later Absence of functional T cells happens if the thymus doesn’t develop normally (DiGeorge Syndrome) Immunity and Cancer Cancer cells are… immortalized, transformed, may undergo metastasis Causes of cancer: 1. Inherited mutation 2. Environmental causes 3. Genome alterations (e.g. rearrangements of DNA, increases in gene copy number, “jumping genes” aka transposable elements) 4. Oncogenic (=cancer causing) viruses (e.g. DNA or RNA virus) Ames test The genomic rearrangements necessary for the proper assembly of the immunoglobulins makes the immune system vulnerable to several cancers. Burkitt’s lymphoma: tumor cells due to impaired immunity function Retrovirus: type of RNA virus that can cause cancer How do they cause cancer? 1. Integration of the provirus near a gene important for cell growth and division 2. Retroviruses can carry a gene for cell growth and division as a passenger in their genome (e.g. sarcomas, lung and colon carcinomas) Immunity and HIV: exhausting the immune system - Spread by the transfer of white blood cells from one infected person to another - 28 million have died, 34 million are living with it - Likely originated by more than one cross-species infection by SIV (simian immunodeficiency virus) in ‘bush meat’ hunting parties - HIV enters helper T cells, using CD4 proteins as receptors - Once gp120 binds to CD4, a conformational change allows gp120 to interact with chemokine co-receptors (CCR5 or CXCR4) - Once stabilized gp41 (associated with gp120) enters the host cell and the two membranes (viral and host cell) fuse - HIV also enters other cells such as the antigen presenting cells, cells lining the digestive trace, and microglial cells The life cycle of HIV 1. HIV attaches to a host cell plasma membrane 2. HIV enters the host cytoplasm and the capsid is removed by enzymes 3. Reverse transcriptase catalyzes the synthesis of single-stranded DNA that is complementary to the viral RNA 4. The DNA strand then serves as a template for the synthesis of a complementary DNA strand, resulting in double-stranded DNA 5. The dsDNA is transferred to the host nucleus and the enzyme integr
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