Unit 3 Biology Study Cards

CHEMICAL NATURE OF PROTEINS Contain carbon, hydrogen, oxygen, nitrogen and some contain sulphur Proteins are made from smaller organic molecules called amino acids, of which there are 20 different types Peptide bonds form between amino acids monomers to forma long sequence of amino acids (polymer) called a polypeptide. The polypeptide or combination of polypeptides makes the protein. The bonds between amino acids are formed by a condensation reaction (water is lost)

PROTEIN SYNTHESIS Protein synthesis is the manufacture of proteins. The organelles involved in protein synthesis are: the nucleus, ribosomes, rough endoplasmic reticulum, Golgi apparatus and secretory vesicles. DNA provides the instructions for protein synthesis which occurs at the ribosomes in the cytosol. Protein synthesis occurs in 2 stages Transcription: DNA is used as a template to produce messenger RNA Translation: Ribosomes read mRNA, tRNA brings amino acids from the cytosol to the ribosome and adds them onto a growing polypeptide chain.

PROTEIN STRUCTURAL LEVELS Primary: the specific linear sequence of an amino acid in the protein O – O – O – O whole thing = polypeptide chain (Polymer) O = amino acid (monomer) - = peptide bond Secondary: the folding of the amino acid chain caused by hydrogen bonds Alpha Helix Beta pleated sheet /\/\/\/\/\/\/\/\ /\/\/\/\/\/\/\/\ /\/\/\/\/\/\/\/\ Random coil Tertiary: total irregular folding of the polypeptide chain Tertiary structure of Tertiary structure of Quaternary structure of protein A Protein A Protein B and Protein B, interacting together + = Quaternary: two or more polypeptide chains interacting to form a protein

PROTEIN FUNCTIONS MOTILITY Proteins are involved in cell movement e.g. Actin and myosin work together to move muscles or movement of an organism e.g. cilia and flagella are protein based. CATALYSE BIOLOGICAL REACTIONS Enzymes are proteins which catalyse biological reactions, decreasing the activation energy and causing the reaction to occur faster than it would normally. STRUCTURE Proteins such as keratin and collagen are responsible for providing strength and support. RECEPTORS Protein receptors label cells as self, provide binding sites for hormones and are involved in the transmission of nervous impulses.

PROTEIN FUNCTIONS DEFENCE IN ANIMALS Animals produce specific antibodies (immunoglobulins) in response to foreign antigens which cause the foreign matter to clump together facilitating phagocytosis. Many animals produce toxins as a non specific defence mechanism e.g.. bees, snakes, toads DEFENCE IN PLANTS Plants produce toxins e.g.. oleander, deadly nightshade and rhubarb. MATERIAL TRANSPORT Substances can be transported into cells via carrier proteins or protein channels. COMMUNICATION Many hormones are protein based as are neurotransmitters and neurohormones.

THE PROTEOME The proteome is the set of proteins produced by a cell. Proteomics is the study of the structure and function of proteins as well as the way they function and interact with each other. We study the proteome as proteins do not normally function in isolation from each other - they tend to work together.

APPLICATIONS OF THE PROTEOME MEDICAL DIAGNOSIS All cells have a complement of proteins they produce. When a protein is not produced, or it is produced at an incorrect level this information can be used as a diagnostic tool. MONOCLONAL ANTIBODIES Monoclonal antibodies can be used to detect the presence of specific antigens. Pregnancy kits are an example of this as they contain human chorionic gonadotrophin which is an indicator of pregnancy. DESIGNED DRUGS (also called rational drug design) If the shape of an antigen is known a drug can be designed which has a complementary site so that it can bind to and inactivate the antigen. Example: Glivec A drug designed to treat myeloid leukemia (ML). In ML white blood cells replicate uncontrollably. Glivec has been designed to block the pathway that allows this uncontrolled replication.

APPLICATIONS OF THE PROTEOME RELENZA A drug designed to bind to neuramidase on the surface of influenza virus preventing the release of virions and stopping the replication and spread of the virus.

CHEMICAL NATURE OF LIPIDS Lipids are synthesised in the smooth ER. They are hydrocarbons, containing the elements carbon, hydrogen and oxygen. Lipids are generally made up of triglycerides – a glycerol molecule with 3 fatty acid tails attached.

CHEMICAL NATURE OF LIPIDS SATURATED FATTY ACIDS In saturated fatty acids, all of the bonds in the hydrocarbon chain are single bonds. Individual chains can pack tightly together forming a solid lipid. Animal fats are generally saturated UNSATURATED FATTY ACIDS In unsaturated fatty acids, there are 1 or more double bonds in the hydrocarbon chain. This means that the chains cannot pack as tight due to the kink in the lipid chain. This results in a liquid lipid, plants fats are generally liquids

FUNCTIONS OF LIPIDS AMPHIPHATIC FATS These are partially soluble in water e.g. phospholipids have a polar hydrophilic head made of glycerol and a hydrophobic tail made up of 3 molecules of fatty acids. STRUCTURAL Phospholipids act as the structural component of cell membranes. Cholesterol molecules prevent the phospholipids from packing together too tightly and rupturing. This assists to maintain the fluidity of the membranes. MATERIAL TRANSPORT The phospholipid membrane regulates movement of materials into and out of cells based on the size, polarity, solubility and charge of the substances involved. DEFENCE Glycolipids are involved in cell recognition - identifying the difference between self and non-self. Blood types - different glycolipids on the surface of red blood cells cause the different blood types Waxes such as ear wax in animals and the cuticle in plants have a role in the first line of defence. WATERPROOFING Waxy substances repel water and can be used to prevent water loss

FUNCTIONS OF LIPIDS ENERGY Lipids have a high proportion of Hydrogen atoms relative to Oxygen atoms and yield more energy than the same mass of carbohydrates. Excess triglycerides are stored as adipose tissue. THERMAL INSULATION Triglycerides conduct heat very slowly. Marine animals often have a thick layer of subcutaneous fat (located under the skin) called blubber which keeps metabolic heat inside the body. ELECTRICAL INSULATION The axon of a nerve cell is surrounded by a fatty material called myelin. It helps maintain nerve conductivity by preventing signal loss. It also increases speed of nervous conduction by increasing the diameter of the axon. HOMEOSTASIS Steroid hormones have a lipid component e.g. oestrogen and testosterone. BUOYANCY Triglycerides are less dense than water. Marine organisms with a high lipid content are highly buoyant.

CHEMICAL NATURE OF NUCLEIC ACIDS Nucleic acids are polymers made up of nucleotide monomers. They contain the elements carbon, hydrogen, oxygen, phosphorus and nitrogen. Each nucleotide contains a phosphate group a 5 carbon sugar and a nitrogenous base. In DNA there are 4 bases Thymine and Adenine which are complementary and Guanine and Cytosine which are complementary. In RNA Thymine is replaced with Uracil and deoxyribose is replaced with ribose.

STRUCTURE OF NUCLEIC ACIDS The “backbone” of the molecule consists of alternating sugar molecules and phosphate groups which are joined by covalent phosphodiester bonds. The nitrogenous base is attached to the sugar unit. DNA contains 2 strands, and the complementary bases are joined by hydrogen bonding; mRNA is a single stranded molecule in straight formation; tRNA is also single stranded but has a clover leaf pattern.

FUNCTION OF NUCLEIC ACIDS DNA DNA contains the instructions that code for protein synthesis. mRNA FUNCTIONS Messenger RNA (mRNA) is made up of triplets of bases (codons) which are read by a ribosome to produce a functional protein. Some mRNA also codes for protein channels and other functional proteins within a cell. tRNA FUNCTIONS Transfer RNA (tRNA) transports amino acids from the cytoplasm to the ribosome. It has an exposed anticodon. When the codon and anticodons bind the amino acid is released onto the growing polypeptide chain.

CHEMICAL NATURE OF CARBOHYDRATES Carbohydrates contain carbon, hydrogen and oxygen in a 1:2:1 ratio and have the (general formula (CH2O)n). They come in a variety of forms including: Monosaccharides – simple sugars consisting of 1 sugar monomer e.g. glucose Disaccharides – sugars consisting of 2 sugar monomers e.g. lactose Polysaccharides – sugars consisting of many sugar monomers e.g. starch Glycoproteins – a molecule made up of carbohydrates and proteins. Glycolipids – a molecule made up of carbohydrates and lipids

FUNCTIONS OF CARBOHYDRATES ENERGY PRODUCTION Carbohydrates are the substrate for cellular respiration (e.g. glucose) and are also intermediates during this process (e.g. pyruvate). ENERGY STORAGE Energy is stored in the bonds between the atoms in carbohydrates and released when the bonds are broken e.g. starch in plants and glycogen in animals. STRUCTURAL Carbohydrates are used to build cellular components e.g.. the cellulose cell wall in plants and chitin in arthropod exoskeletons and fungal cell walls COMMUNICATION Glycoproteins act as receptors for hormones and MHC markers identifying “self” cells. GENETIC All nucleic acids contain 5 carbon sugars in their nucleotides – ribose in RNA and deoxyribose in DNA.

ORGANELLES CHLOROPLASTS Chloroplasts are found in autotrophic cells and contain chlorophyll which catalyses photosynthesis They have a double membrane which encloses an enzyme rich liquid matrix ( stroma ) and stacks of thylakoid disks ( grana ). Chloroplasts are unusual in that they contain DNA (like the nucleus and mitochondria)

ORGANELLES MITOCHONDRIA Membrane bound organelles that are located in the cytosol of all eukaryotic organisms. Responsible for aerobic cellular respiration which makes them the main provider of ATP. They have two membranes (not one as in other organelles). The outer membrane covers the organelle and contains it. The inner membrane folds over many times ( cristae ). That folding increases the surface area inside the organelle. The fluid inside of the mitochondria is called the matrix . They are unusual in that they contain DNA (like the nucleus and chloroplast)

ORGANELLES GOLGI COMPLEX Associated with protein production. Stores, modifies and packages proteins into vesicles for exocytosis.

ORGANELLES RIBOSOMES Are found in both prokaryotic and eukaryotic cells Are the site of protein synthesis (translation of mRNA) May be found attached to endoplasmic reticulum (rough ER) or free in the cytosol. Numbers vary, with large numbers being found in secretory cells.

POLARITY When 2 atoms in a covalent compound do not equally share an electron One region of the molecule develops a partial negative charge and the other a partial positive charge. These molecules are referred to as polar . In non-polar molecules the electrons are shared equally. The water molecule shown above is polar – the oxygen atom has a comparatively negative charge and the hydrogen atoms have a comparatively positive charge. The “like dissolves like” rule is used to predict whether a solute will dissolve in a solvent e.g. polar molecules dissolve in polar solvents.

PROPERTIES OF WATER Water molecules are polar because the oxygen atom within the molecule exerts a stronger pull on the shared electrons than the hydrogen atoms causing the water molecule to have partially charged areas. Polarity allows adjacent water molecules to be attracted to each with one another and also gives water many important properties. UNIVERSAL SOLVENT Ionic compounds and polar molecules readily dissolve in water. Water forms hydration shells around ions to prevent them from reforming neutral compounds. Non polar molecules cannot dissolve in water but often form interfaces with it which are frequently the sites of biological reactions. COOLANT Water has a high vapourisation temperature as the hydrogen bonds allow it to absorb a lot of heat before changing state. ADHESION Water molecules are attracted to each other allowing them to move into small spaces by capillary action. DENSITY Solid water is less dense that liquid water. Ice floats on water and insulates it allowing aquatic organisms to survive under ice.

PLASMA MEMBRANE STRUCTURE Composed of a phospholipid bilayer embedded with many proteins. The proteins extend all the way through the bilayer. Cholesterol is embedded between the fatty acid hydrophobic tails and prevents the phospholipids from packing together which prevents the membrane from breaking and keeps the membrane fluid. Glycoproteins extend from the outer surface and they act as receptors and markers.

PHOSPHOLIPID MOLECULES Phospholipid molecules have hydrophilic (attracted to water) phosphate heads and hydrophobic (repelled by water) fatty acid tails. Phospholipids are modified triglycerides with the third tail replaced by the phosphate group. Phospholipid bilayers form because the fatty acid tails are repelled by the watery extracellular fluid and cytosol.

PLASMA MEMBRANE FUNCTIONS MATERIAL TRANSPORT The membrane is selectively permeable Lipid soluble substances pass directly through the membrane by diffusion. Small molecules pass between the phospholipid molecules by diffusion. Large lipid insoluble (or water soluble) substances glucose have to pass through channels such as the carrier proteins by facilitated diffusion. Most gases can pass through by diffusion. Water passes through by a specialised form of diffusion called osmosis Some substances move into the cell against the concentration gradient by active transport. COMPARTMENTALISATION Organelles and their functions are compartmentalised into specific sections of the cell. The membrane surrounding the organelles has the same phospholipid structure as the plasma membrane. Examples of this include the isolation of DNA by the nuclear envelope and containment of enzymes by lysosomes.

PLASMA MEMBRANE FUNCTIONS CELL RECOGNITION AND COMMUNICATION Proteins embedded in the cell membrane act as receptors for hormones. Glycoproteins and glycolipids act as markers enabling the organism to “recognise self” preventing them from being targeted by the immune system. They also help cells to organise themselves into organs and tissues. ISOLATION OF HARMFUL SUBSTANCES Potentially harmful substances are confined in structures Lysosomes and peroxisomes enclose digestive enzymes. The vacuole in plants can also store toxins and pigments

ROLE OF MEMBRANES IN CELLS The plasma membrane and the membranous organelles all have the same phospholipid structure. This is what enables organelles to pass substances between each other via vesicles. Membrane bound organelles have a variety of roles including: Lipid Synthesis by the smooth ER. Containment of DNA by the nuclear envelope. Energy production and transformation occurs in the mitochondria. Entry and exit of substances is controlled by the plasma membrane. Packaging and secretion of proteins in controlled by the Golgi body. The ribosomes (not membrane bound) secrete polypeptides directly into the rough ER. Toxic substances such as enzymes are contained by lysosomes. Cell communication and recognition is governed by proteins in the plasma membrane.

TYPES OF MATERIAL TRANSPORT PASSIVE TRANSPORT Does not involve the use of energy. Substances are transported down a concentration gradient from an area of high concentration to an area of low concentration (it’s not enough to just write from high to low) Includes diffusion, osmosis and facilitated diffusion. ACTIVE TRANSPORT Involves the use of ATP Substances are transported against their concentration gradient from a region of low concentration to a region of high concentration. Example is the sodium/potassium ion pump in nerve cells. VESICLE MEDIATED The substance being transported is enclosed in a vesicle The processes include endocytosis, exocytosis, phagocytosis and pinocytosis

COMPARING TRANSPORT OF SUBSTANCES

FACTORS AFFECTING MATERIAL TRANSPORT PARTICLE SIZE Small molecules such as gases and water will diffuse more rapidly than larger molecules. POLARITY Non-polar substances diffuse faster than polar substances CHARGE Neutral substances can diffuse across a membrane, charged particles cannot HEAT Heat provides kinetic energy making the particles move faster increasing diffusion. SOLUBILITY Lipid soluble substances diffuse across a membrane faster than water soluble substances SURFACE AREA TO VOLUME RATIO Increasing the SA:V ratio provides a greater surface for transport to occur across. STATE OF MATTER Diffusion occurs fastest in gases, then liquids and very slowly if at all in solids

DIFFUSION Factors that increase the rate of diffusion: Increasing the steepness of the concentration gradient Heat provides kinetic energy which causes the particles to move faster Small molecules are further apart, allowing them to mover with more ease Process Definition Direction of movement Energy required Speed of process Substances moved by this process Substances not moved (in or out) Diffusion Net movement of molecules from an area of high concentration to an area of low concentration until equilibrium is reached Down the concentration gradient ATP not required = PASSIVE Slow Molecules, uncharged particles (Solute) Hydrophilic molecules - big molecules (glycogen/ sucrose) Advantages of diffusion Disadvantages of diffusion No energy is required Molecules in the cell that are required, maybe lost if the external has a lower concentration then the internal environment

OSMOSIS This is a special type of diffusion, it is the net movement of free water molecules across a semi-permeable membrane. Net diffusion of water occurs from the dilute to the concentrated solution along its own concentration gradient, this is called the osmotic gradient. The pressure causing the water to move along this gradient is called the osmotic pressure .

ISOTONIC SOLUTIONS An isotonic solution is a solution where equal concentration exists in the cytosol and extracellular fluid (inside and outside the cell). The overall net movement of water is balanced ( no net diffusion occurs). A cell will neither gain or lose solute or water molecules.

HYPERTONIC SOLUTIONS A hypertonic solution has a lower water concentration and higher solute than the cytosol of a cell, water will diffuse out of the cell along the concentration gradient.. If a plant cell is placed into a hypertonic solution, water will move out of the cell. The cellular membrane will pull away from the cell wall and the cell will become flaccid. If an animal cell is placed into a hypertonic solution, water will move out of the cell and the cell will shrink.

HYPOTONIC SOLUTIONS A hypotonic solution has a higher water concentration and a lower solute concentration than the cytosol of a cell. As a result water diffuses into the cell following its concentration gradient. If a plant cell is placed into a hypotonic solution water will move into the cell. The cellular membrane will push against the cell wall, creating turgidity, but the cell does not lyse. If an animal cell is placed into a hypotonic solution water will move into the cell, the cell swells and may lyse.

FACILIATED DIFFUSION Facilitated diffusion is a form of passive transport that occurs when particles diffuse across a membrane with the aid of transport proteins. Charged particles (ions) dissolve in water and are transported through channel proteins that only open when the correct signal occurs. Large water soluble molecules such as proteins and glucose bind to carrier proteins which then change shape and release them on the other side of the membrane.

PROTEIN CHANNELS VS CARRIER PROTEINS Both of these structures are found spanning the plasma membrane, and although they are both specific, their mode of action is different. Carrier proteins work by allowing molecules to bind to them and then change their conformation releasing the molecule on the other side of the membrane. Protein channels are tubes filled with water that produce pores in the plasma membrane. Water soluble particles diffuse through them rapidly.

ACTIVE TRANSPORT Active Transport is the net movement of dissolved substances into or out of cells against a concentration gradient. Requires energy in the form of ATP Involves the use of a carrier protein in the cell membrane to actively transport the substance into or out of a cell.

COMPARISON OF TRANSPORT METHODS

THE ACTION OF ENZYMES Enzymes are catalytic proteins that speed up biological reactions by decreasing the activation energy of the reaction. They do not increase the amount of product – just the speed at which it is produced.

THE ACTION OF ENZYMES Enzymes have an active site which is where the enzyme binds to. The site of an enzyme is specific – it can only bind substrates of the correct chemical configuration. Originally this was called the lock and key model and it has now been adapted to the induced fit model. Specificity is caused by the shape of the enzyme. The tertiary level of proteins provides the enzyme with it’s shape. The enzyme is released unchanged at the end of the reaction and can be reused.

THE ACTION OF ENZYMES Catabolic enzymes break down large molecules into smaller products. Energy is released when the bonds are broken (exergonic) e.g. process of cellular respiration Anabolic enzymes use small molecules as substrates to produce larger products e.g. process of photosynthesis. These reactions are endergonic (require energy) as it takes energy to make bonds.

FUNCTIONS OF ENZYMES Enzymes have a wide range of function which are essential for life. Energy (ATP) Production e.g. glycolysis, anaerobic respiration, oxidative phosphorylation and the citric acid cycle. Synthesis of energy creating compounds from inorganic substrates e.g. photosynthesis and chemosynthesis Obtaining nutrients e.g. digestive enzymes such as lipases, proteases and amylases. Removal of toxic wastes e.g. catalase breaks down toxic hydrogen peroxide that is produced by our metabolisms

EFFECT OF ENZYME CONCENTRATION Enzymes contain the active site for substrates to bind to. Increasing the concentration of enzyme will increase the rate as more active sites are available. The limiting factor then becomes the substrate concentration .

EFFECT OF SUBSTRATE CONCENTRATION The rate of reaction increases with increasing substrate concentration up to the point of saturation. After this point any further increase in substrate concentration produces no significant change in reaction rate. This is because the active sites of the enzyme molecules at any given moment are saturated with substrate – the reaction is producing as rapidly as possible. The enzyme/substrate complex has to dissociate before the active sites are free to accommodate more substrates.

EFFECT OF TEMPERATURE Heat affects the amount of kinetic energy of a particle, the greater the heat, the faster the particle will move. All enzymes have an optimum temperature at which they work best. The point after optimum is called the critical point and it is at this point that the enzyme begins to denature (lose it’s shape and therefore its function), decreasing the reaction rate. A reaction performed at a less than optimum temperature will also be slow, but only because of the lower kinetic energy of the particles, the enzyme is not denatured by being cooled..

EFFECT OF pH All enzymes work best in a narrow pH range called the optimum pH. Optimum pH is governed by the normal location and function of the enzyme e.g. amylase which breaks down starches in the mouth has an optimum of approximately 7 whereas proteases in the stomach have an optimum pH of approximately 2. Altering the pH in either direction begins to denature the enzyme, preventing it from binding to the substrate and decreasing the reaction rate.

EFFECT OF INHIBITORS NON COMPETITIVE INHIBITORS Are usually products of the reaction. Bind to a regulatory site (not the active site) This binding changes the shape of the active site and prevents binding between the enzyme and substrate COMPETITIVE INHIBITORS Have a similar conformation (shape) to the substrate Act by binding to the active site and blocking the binding between enzyme and substrate.

METABOLISM AND METABOLIC PATHWAYS Cellular metabolism is the sum of the chemical reactions that occur in an organism. A metabolic pathway is a series of reactions in which the product of one reaction is the reactant for the next step.

DEFECTIVE METABOLIC PATHWAYS Diseases such as phenylketonuria are caused by defective metabolic pathways. One of the links in the pathway fails and as a result all subsequent products are not produced. The simplest method of bypassing a defective stage in a metabolic pathway is to provide the product that would normally be produced.

PHOTOSYNTHESIS Is an endergonic, carbon fixing reaction that occurs in the chloroplasts of plants. There are 2 main stages – the light dependent and light independent stages. The inputs are carbon dioxide and water and the outputs are glucose (later used to generate energy) and oxygen (a waste product).

LIGHT DEPENDENT STAGE Stage 1 of Photosynthesis which occurs in the grana of the chloroplast. Chlorophyll absorbs light. Energy splits water into H+ ions, electrons and oxygen gas. Electrons are passed down an electron transport chain releasing energy The energy is used to pump H+ ions to the stroma creating an ion gradient that allows phosphorylation of ADP. NADP forms NADPH and transports H+ to the light independent stage.

LIGHT INDEPENDENT STAGE Stage 2 of Photosynthesis, also called Calvin cycle or carbon reduction cycle Occurs in the stroma of the chloroplast ATP ADP + Pi Carbon Dioxide Glucose Carrier H+ Carrier molecule The energy to covert the low energy CO2 to the high energy glucose C 6 H 12 O 6 , comes from ATP breaking down to ADP + Pi and the loaded acceptors unload hydrogen (H+) NADP transports H+ to Calvin cycle from the light independent stage Calvin cycle joins H+ ions, CO 2 and a 5C intermediate to produce a 6C sugar (glucose)

ANAEROBIC RESPIRATION Anaerobic respiration refers to the oxidation of molecules in the absence of oxygen. Krebs cycle and Electron transport chain don’t work without oxygen It occurs in 2 stages – glycolysis and fermentation. Fermentation requires another electron acceptor to replace oxygen . IN PLANTS Process occurs in the cytosol Ethanal is the final acceptor Products are ethanol and carbon dioxide Ethanol is cytotoxic but cannot be re-metabolised

ANAEROBIC RESPIRATION IN ANIMALS This process occurs in the cytosol Pyruvate is the final acceptor The only product is lactic acid Lactic acid can be converted back into pyruvate and converted to carbon dioxide and water via the Krebs Cycle. Oxygen debt is incurred during anaerobic fermentation so large quantities of oxygen are taken in when the organism switches back to aerobic respiration.

GLYCOLYSIS Glycolysis is the first stage of cellular respiration and occurs in the cytosol It is an anaerobic processes where glucose is phosphorylated and converted to pyruvate (a 3 carbon substance) There is a net production of 2 ATP molecules (4 are produced but 2 are used up in the process) Glycolysis is the only anaerobic source of ATP, if anaerobic respiration continues either ethanol and carbon dioxide are produced by plants or lactic acid by animals.

THE KREBS CYCLE Occurs in the matrix of the mitochondria 2 Pyruvate molecules produced in glycolysis enter the mitochondrion Pyruvate is then converted to Acetyl CoA Acetyl CoA enters the Krebs cycle and 2 CO 2 molecules are released Hydrogen ions are released form loaded acceptor molecules (4 NADH and 1 FADH 2 ) 2 ATP are released

THE KREBS CYCLE 2 Pyruvate enter Mitochondrion 2 ATP are released Pyruvate is converted to Acetyl CoA 2 CO 2 are released Acetyl CoA enters the Krebs Cycle Hydrogen ions that are released form loaded acceptor molecules 4 NADH And 1 FADH 2 are released 1. 2. 3. 4. 5. 6.

THE ELECTRON TRANSPORT CHAIN Definition : process involving the stepwise transport of electrons to a final electron acceptor, such as oxygen (in aerobic cellular respirations); ultimately, it creates an electrochemical gradient across membranes to drive the phosphorylation of ADP to yield ATP. High energy electrons are passed down the chain, releasing energy as they go. This energy released is used for phosphorylation of ADP to ATP. Hydrogen ions are also passed down the chain. The hydrogen ions are accepted by oxygen producing water. Total ATP yield per glucose = 34 (17 per pyruvate)

PHOSPHORYLATION Phosphorylation is the addition of a phosphate group to any organic molecule, increasing its reactivity. Phosphorylation is an important means of recycling energy as it is reused to recharge ADP, producing ATP.

OXIDATIVE PHOSPHORYLATION A phase of aerobic respiration that occurs in the cristae of the mitochondria. The cytochrome system transports hydrogen atoms from glycolysis and Krebs cycle When the carbon atoms of glucose molecules are oxidized some of the resulting energy is used to add a phosphate to ADP creating ATP Most of the energy remains in the carbon hydrogen bonds and in the electron carriers NAD and FAD In the final stage of the oxidation of glucose the electrons with high energy are passed sequentially in a controlled step by step process to lower their energy level.

AEROBIC AND ANAEROBIC RESPIRATION COMPARISON

MAINTAINING BLOOD PH The optimum pH for human blood is 7.35 -7.45 (death will occur if blood pH deviates by more than about 0.4 units). Blood pH is maintained by the carbonic acid/bicarbonate buffer system. Carbonic acid is a weak acid and bicarbonate is its conjugate base. Acids produce hydrogen ions in solution (H + ) and bases accept them Carbonic acid is produced when carbon dioxide reacts with water in the blood decreasing pH. It then dissociates producing bicarbonate ions which raises the pH level of blood. The reactions in the buffering system are reversible allowing fine control of blood pH.

CELLULAR COMMUNICATION Communication between cells governs all cellular activities such as transport, growth, secretion of products and apoptosis (programmed cell death) The important aspects of cellular communication include: Production of a signal when a change occurs Detection of the signal Signal transduction (transfer) to the target tissue Response by the target tissue Switching off the signal after the response has occurred, which occurs by negative feedback or by breaking down one of the molecules in the response pathway. The changes may be caused by internal factors e.g. change to blood glucose levels or external factors e.g. change in light levels.

SIGNAL TRANSDUCTION Signal transduction involves getting a signal from a target cells exterior to the cells interior during which the cell converts one kind of signal into another. The target cell may respond by: Altering gene expression – production of proteins may increase or decrease Activate or deactivate enzymes, altering cellular metabolism Altering the permeability of the plasma membrane, affecting the cells ability to take up or release certain substances e.g. if a neuron takes up acetylcholine it’s membrane becomes more permeable to sodium and potassium ions.

HOMEOSTASIS Homeostasis is the maintenance of a relatively stable internal environment despite external fluctuations. Homeostasis is responsible for maintaining the internal environment within narrow tolerance limits. Biochemical processes can be disrupted if these conditions are not kept within those narrow limits e.g. enzyme function is affected by blood temperature and pH. Organisms with wider tolerances are more likely to survive severe challenges in the external environment. Homeostasis in animals is governed by the hormonal and nervous systems Homeostasis in plants is governed by the hormonal system Homeostasis in micro-organisms is more limited as they are exposed directly to the external environment, they either move away or regulate their internal environment by altering the permeability of their cell membrane .

NEGATIVE FEEDBACK Negative feedback is a response mechanism where the response counteracts the effect of the stimulus, returning the body back to normal. It is important to remember that the problem may be an excess or a deficiency. The stages that occur in negative feedback are as follows: A change occurs which affects a key variable which causes the production of a signal. The signal must be detected by a receptor The signal is transferred to a control centre. The control centre sends another signal (to an effector) An effector (muscle or gland) responds to the signal The original signal is decreased and the process continues until it is switched off

RECEPTORS CHEMORECEPTORS Stimulated by chemical changes e.g. respiratory gases, water, glucose. Located in major arteries, taste buds, nose, lungs and brain Involved in taste, smell and regulation of substances in the internal environment MECHANORECEPTORS Stimulated by forces that change the shape of sensory nerve endings e.g. sound, vibration, touch or pressure. Located in skin, ears, lungs and joints PHOTORECEPTORS Stimulated by light Located in eyes and other light sensitive areas THERMORECEPTORS Stimulated by temperature changes Located in the skin and brain Involved in temperature regulation PAIN RECEPTORS Stimulated by pain Located in the skin (nerve endings) Involved in defence by involuntarily protecting the body when it experiences pain

THE HORMONAL SYSTEM The hormonal system works by secreting hormones which can only bind to cells with the appropriate receptor. ANTAGONISTIC HORMONES These are hormones with opposing effects. Balanced use of these hormones allows for finer control Example Insulin decreases blood glucose concentration while glucagon increases blood glucose concentration ENDOCRINE HORMONES These hormones are secreted directly into the blood stream and are circulated until they reach the target tissue. EXOCRINE HORMONES These hormones are secreted through a duct directly to the target tissue.

BLOOD GLUCOSE REGULATION Blood glucose is regulated by 2 antagonistic amino acid hormones; insulin and glucagon which are secreted by the pancreas. WHEN BLOOD GLUCOSE IS HIGH Insulin is secreted into the blood stream and targets mainly the liver and muscle cells Insulin binds to a kinase receptor which acts as a second messenger Kinase activates a range of other proteins The responses include: Increasing the rate of glucose uptake by cells, liver cells converting glucose to glycogen and storing it, glucose and glycogen being converted to fat and stored, inhibiting the conversion of glycogen back to glucose and inhibiting the secretion of glucagon. WHEN BLOOD GLUCOSE IS LOW Glucagon is secreted into the blood stream and targets mainly the liver and muscle cells Glucagon binds to a receptor on the plasma membrane and uses cAMP as a second messenger. Cyclic AMP activates a range of other proteins The responses include: decreasing the rate of glucose uptake by cells, liver cells converting glycogen back to glucose and releasing it into the blood stream, stored fats being converted into carbohydrates and inhibiting the secretion of insulin.

DIABETES Diabetes is a condition caused by a breakdown in the insulin pathway. Type 1 diabetes is a failure of the body to produce insulin. Type 2 diabetes is a failure of the muscle and liver cells to respond sufficiently to insulin. These people may control diabetes by diet. When looking at a graph of blood glucose a diabetic can be identified by: A higher initial concentration of blood glucose (over 8mmol/L) When glucose is taken in (called a glucose tolerance test), the blood glucose level of the diabetic will rise at a much greater rate and it will also take much longer to return to the original level. Research is being performed into the possibility of implanting an internal pump which will monitor glucose concentration and release insulin as required, producing an effect similar to that of normal homeostasis. This method would only work for those with type 1 diabetes as those with type 2 can produce sufficient insulin already.

AMINO ACID HORMONES Amino acid hormones utilise the second messenger system. The receptor for amino acids is located on the outside of the plasma membrane. The first messenger is the binding between the hormone and the receptor. This stimulates production of a second messenger inside the cell e.g. cAMP The second messenger system is rapid is it activates enzymes already present in the cell causing the response.

STEROID HORMONES The receptor for steroid hormones is located within the cytosol. Steroid hormones are able to diffuse directly across the plasma membrane and bind to the receptor. The receptor/hormone complex moves to the nucleus, interacting with DNA and thus altering protein production. The action of steroid hormones is slower than that of amino acid hormones as it takes time to activate genes in the DNA and then adjust protein production. Cholesterol is the basis for steroid hormones which include: Thyroxine. Testosterone and Oestrogen.

COMPARISON BETWEEN STEROID AND AMINO ACID HORMONES

PHEROMONES Chemicals secreted by an organism designed to be detected by others of the same species. They are unusual as their action is external not internal. COMMUNICATION PHEROMONES. These pheromones may be used to mark trails e.g. ants or they may be flee pheromones or danger pheromones designed to warn others. SEXUAL PHEROMONES These pheromones are secreted by organisms seeking a mate. However they can be misused by predators who use them to attract prey, flowers can mimic them to attract pollinators and humans use them to attract insects that are considered pests.

PLANT GROWTH REGULATORS Plants lack a nervous system so their responses are governed by hormones or chemical regulators.

THE NERVOUS SYSTEM Consists of the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord, the PNS consists of sensory and motor nerves. Neurons are the functional units of the nervous system. Signal transduction (nerve transmission) is accomplished by electrochemical means. The electrical part of the signal occurs when the impulse is transmitted along the axon of a neuron. The chemical part of the signal occurs between 2 cells and involves the secretion of a neurotransmitter into the synapse.

NEURON STRUCTURE There are several kinds of neurons which have different appearances to each other, but all neurons have a cell body which controls the function of the cell, axon which conducts impulses away from the cell body and dendrites which take in information and carry impulses towards the cell body. The gap or junction between the axon of one neuron and the dendrites of the next, or between the axon and an effector is called a synapse. SENSORY (AFFERENT NEURONS) These include sensory receptors that monitor internal and external environments and transmit impulses from receptors to the CNS. CONNECTING NEURONS (INTERNEURONS) These are located in CNS and transmit nervous impulses between neurons in the CNS MOTOR (EFFERENT) NEURONS These have many extensions called dendrites that receive signals from other neurons and a single axon that transmits signals from the CNS to other neurons, muscles or glands.

NERVE IMPULSE TRANSMISSION When a neuron is at rest the inside is negatively charged compared to the outside (it is polarised) This is called the resting potential . Stimulation of a receptor causes depolarisation of the inside of a nerve cell (the inside becomes slightly less negative). If the depolarisation is large enough it generates an action potential. The sequence of events is: 1) The cell membrane becomes more permeable and Ion channels for sodium in the membrane open and the sodium ions diffuse from the interstitial fluid into the cytoplasm of the axon 2) The sodium ions are positive in charge so they make the cytoplasm less negative (the resting potential of the cell decreases and it depolarises 3) If the depolarisation reaches the threshold level then an action potential is generated. If not nothing happens. 4) The sodium channels close and the potassium channels open. 5) Potassium diffuses out of the cytoplasm reducing the charge inside the cell. This is called repolarisation. 6) The potassium channels close. 7) The resting potential is restored by the sodium/potassium pump. The ions are transported back across the membrane so that the original concentration of ions is restored.

NERVE IMPULSE TRANSMISSION As a result the cell is positive for a while before it becomes negative again. The changes are called the action potential. After the action potential has occurred the sodium and potassium ion channels close and the ion concentration return to their resting concentrations during the refractory period. Axons cannot conduct any further action potentials during this period. The above has only described one area of the neuron and not how the impulse is carried along the neuron, this happens by another chain reaction. Once an impulse is made, a local current is set up between the area where there is an action potential and the resting area next to it. The flow of some Na+ sideways towards the negative area next to it causes the Na+ channels in that area to open and depolarisation to occur there. That way, the action potential is moved down the neuron.

DIFFUSION OF NEUROTRANSMITTERS When an impulse arrives at the presynaptic knob secretory vesicles transport neurotransmitters to the membrane. The neurotransmitters are released into the synapse and diffuse to the next cell. They are taken up stimulating the opening of sodium channels, generating an action potential. The neurotransmitters are then broken down by enzymes to prevent continuous firing of nervous impulses.

NEUROTRANSMITTERS VS NEUROHORMONES NEUROTRANSMITTERS A neurotransmitter is a substance secreted by a neuron or neurosecretory cell. It’s purpose it to carry the action potential across the synapse to the next cell. Neurotransmitters can only affect cells in the direct pathway of the impulse. NEUROHORMONES A neurohormone is a hormone secreted by neurosecretory cells (usually in the brain). They differ from neurotransmitters as they can affect cells at a distance from the secretory cell.

THE REFLEX ARC This response is involuntary (governed by the spinal cord, not the brain) which responds rapidly and then also sends a message onto the brain to make you aware of the stimulus. A monosynaptic response is the simplest kind of reflex and only involves 2 nerves- a sensory nerve and a motor nerve. The most common monosynaptic response is the knee-jerk reaction.

POSITIVE FEEDBACK Positive feedback is a response mechanism where the response increases the effect of the stimulus, moving the body further away from the normal condition. Positive feedback can be harmful as it often occurs when the negative feedback system has failed e.g. during fever the bodies temperature can be reset and continue to rise leading to heat stroke. Positive feedback can also be useful examples of this include contractions during childbirth, production of milk during lactation and production of clotting factors in blood after an injury.

DISEASE A disease is any condition that interferes with how an organism, or part of an organism functions. INFECTIOUS DISEASES Are transmittable between organisms Are caused by pathogens or pathogenic agents The organisms causing infectious diseases may be non-cellular, single celled or multicellular. NON-INFECTIOUS DISEASES These conditions are not transferable (except genetic conditions) They include environmental diseases caused by lifestyle or exposure, genetic diseases which are inherited from parents and autoimmune diseases where the immune system attacks the body.

TRANSMISSION OF INFECTIOUS DISEASE Infectious diseases can be transmitted by a variety of means. DIRECT CONTACT Either by touching an infected individual e.g. chicken pox or by coming into contact with bodily fluids from an infected person e.g. HIV INGESTION Consumption of contaminated water e.g. typhoid, giardia or of contaminated food e.g. salmonella AEROSOLS Sneezing or coughing creates aerosol droplets, containing infectious particles which can then be inhaled e.g. cold VECTORS Some disease causing organisms are carried by other organisms e.g. the anopheles mosquito carries the protozoan responsible for malaria.

STAGES OF INFECTIOUS DISEASE The stages that occur during an infectious disease are: 1) Entry of the pathogen 2) Incubation period - this is the stage where the pathogen replicates increasing numbers 3) Symptoms (experienced by the person e.g. aches and lethargy) and signs (capable of being observed by others e.g. fever and rashes). These can often be used in diagnosis. Symptoms are caused by tissue damage, ingestion of toxins, production of toxins and overreaction of the immune system

BACTERIA Bacteria are single celled prokaryotic cells. Many have beneficial purposes e.g. nitrogen fixation while others are pathogens (disease causing) They have a cell wall of peptidoglycan (protein/carbohydrate mixture) instead of cellulose. Some bacteria are motile and use flagella or fimbriae to move. Some species have an outer gelatinous, sticky coating which aids them attaching to a host cell. In adverse conditions some species are able to form endospores which protect them against water loss, temperature and chemicals. Bacteria generally reproduce by binary fission, a form of mitosis, which is very rapid. Some bacteria are aerobic whilst others are anaerobic. They come in a variety of shapes: round (cocci) rod shaped (bacilli), comma shaped (vibrio) and spiral shaped (spirilli or spirochete). Bacteria can be grown on media such as agar enabling us to study them. Bacteria can act in several ways: directly attacking a host cell, secreting toxins or interfering with the hosts immune system.

PROTOZOA Protozoa are single celled eukaryotic cells. They have a life cycle with several stages and have 2 or more hosts. The host where they are normally found is called the natural reservoir. This host is normally the secondary host (where it is found in an immature form). This host acts as a vector which then transfers the protozoa to the primary host where it reaches adulthood. We do not have many drugs that can treat conditions caused by these organisms, instead we take preventative measures e.g. insecticides

ENDOPARASITES Are multicellular organisms found living inside the body of a host. Include worms and flukes. Have a multi stage life cycle and tend to have 2 or more hosts. Some are transmitted by the ingestion of encysted food, others have forms that can move between hosts. Are parasitic as well as pathogenic. The parasite benefits at the expense of the host.

ECTOPARASITES These are multicellular organisms found on the outer surface of a host. Although some can cause diseases they are usually the vector, not the direct cause. They include ticks, fleas, lice, mosquitoes, leeches etc. They are comparatively easy to detect and remove. They are more subjected to external conditions than internal parasites.

VIRUSES Viruses are non-cellular pathogens. They are considered non-cellular as they can only reproduce inside a host cell The stages in viral infection are attachment to the host cell, penetration, uncoating and replication of genetic material. They can be released from the host cell by budding or by lysing the host cell. Antibiotics are useless against them. They can only be stopped by killing the host cell before viral replication occurs (the host cell commits apoptosis) It is difficult to study viruses as they can only be grown in living cells.

VIROIDS AND PRIONS VIROIDS Viroids are pathogenic agents. Unlike viruses viroids lack a protein coating (capsid) They consist of a single circle of unenclosed RNA. They are only known to infect plants PRIONS Are non cellular pathogenic agents Are unenclosed proteins They can infect plants but mainly affect animals e.g. scrapie, mad cows disease, kuru

DEFENCE SYSTEMS There are 3 levels of defence in the human immune system. The first two levels are non-specific (will act the same way towards any pathogen) The third level is specific which means that it targets specific pathogens. The innate immune system is non specific and cannot adapt – so it is levels 1 and 2 The third level of immunity is adaptive and acquired – gained from being exposed to specific pathogens. 1 st LEVEL OF DEFENCE This level is to prevent entry of a pathogen and may be physical structures or chemicals. 2 nd LEVEL OF DEFENCE This level operates inside the body and is responsible for inhibiting or destroying pathogens. THIRD LEVEL OF DEFENCE This level operates inside the body but only when the foreign antigen has been identified. It is either cell mediated (T cells) or antibody mediated (B cells)

SPECIFIC AND NON SPECIFIC DEFENCE

SELF VS NON-SELF It is important that our immune system be able to tell the difference between cells that are part of the body and cells that aren’t. The immune system uses protein markers on the surface of the cell to tell the difference between “self” and “non-self” cells. These markers are called MHC markers (major histocompatibility complex) All nucleated cells contain class 1 MHC markers B cells, T cells and macrophages have class 2 MHC markers. MHC proteins complex with antigen fragments on the surface of antigen presenting cells. This allows the helper T cell to recognize the antigen and stimulate B cells and cytotoxic T cells to launch an immune response.

ANTIGEN Antigens are substances that stimulate the production of an antibody. They can include toxins, and the surfaces of foreign pathogens or parasites such as bacteria, viruses foreign blood cells, and the cells of transplanted organs. Antigens are often proteins based but they can also be lipids, polysaccharides and nucleic acids. Antigens are neutralised by antibodies.

FIRST LINE OF DEFENCE The first line of defence are a variety of physical and chemicals barriers that are designed to keep foreign organisms and substances out of the body. These defences are part of our innate immune system – they are non-specific, cannot adjust to different situations and will always respond in the same way.

FIRST LINE OF DEFENCE MUCUS SECRETING AND CILIATED LININGS These are found lining the respiratory, reproductive, urinary and gastrointestinal tracts. The sticky mucus traps foreign substances which are then removed by cilia. Cilia are small hairlike structure that move in waves. INTACT SKIN Intact skin forms a physical barrier that most pathogens cannot pass through. SECRETIONS Secretions include tears, sweat, saliva, urine and gastric juices. Secretions have a range of actions Some such as sebum in the skin or gastric juices have a pH that is unfavourable to micro organisms. Some such as saliva, tears and urine flush micro organisms away Some such as tears and sweat contain chemicals that destroys bacterial cell walls. NATURAL FLORA These are the (usually) harmless populations of bacteria that exist on outer surfaces. Their presence inhibits the ability of pathogens to colonise these surfaces.

SECOND LINE OF DEFENCE The second line of defence is also innate and non-specific. These mechanisms may be physical or chemical in nature. FEVER Raises the body temperature and metabolic rate. Speeds up blood flow including delivery of white blood cells to the site of the infection. Increases effectiveness of interferon Increases the release of interleukin 1 which speeds up the immune system The stages in fever are: A pathogen or toxin is taken into the body. Macrophages ingest the foreign substance and release interleukin 1 into the bloodstream Interleukin 1 causes the body to reset the bodies thermostat to a higher temperature. This initiates fever

SECOND LINE OF DEFENCE INTERFERON Interferon is a antiviral chemical. It is released from a host cell when it is colonised by a virus. Interferon spreads to neighbouring cells, which take it up and then start producing anti viral enzymes – these degrade the viral DNA preventing the host nucleus from making more copies of the viral DNA. This prevents the virus from colonising nearby cells and spreading further.

SECOND LINE OF DEFENCE COMPLEMENT Complement is a protein that is continually present in blood. It assists phagocytes to recognise foreign antigens by attaching to the pathogen and acting as a marker which attracts more phagocytes. Complement is able to lyse bacterial cell walls (although it is useless against viruses.) When the bacterial cell contents spill into the host more macrophages are attracted.

SECOND LINE OF DEFENCE PHAGOCYTOSIS Phagocytes are white blood cells that are produced in bone marrow and travel through the circulatory and lymphatic system e.g. monocytes and neutrophils They have the ability to squeeze through the capillary walls and move into body tissues in order to engulf foreign material. The stages of phagocytosis are: 1) The bacteria is attracted to the membrane of the phagocyte. 2) The bacteria are then engulfed by the phagocyte and are encapsulated in a vesicle called a phagosome. 3) Lysosomes form inside the phagocyte and fuse with the phagosome. 4) The enzymes in the lysosome digest the bacteria. 5) After the phagocytes die they form pus. Macrophages are large cells, but sometimes a single macrophage is not big enough to engulf a pathogen. If this occurs lots of macrophages will bind to the pathogen in an attempt to engulf and destroy it. Macrophages are mainly involved in the second level of defence, but also have a role in promoting the third level of defence. After they ingest a pathogen they display it's antigen on their surface. This attracts more phagocytes, and also promotes action by T and B cells.

SECOND LINE OF DEFENCE PHAGOCYTOSIS

SECOND LINE OF DEFENCE BLOOD CLOTTING Blood clotting occurs when a blood vessel is torn or ruptured in order to maintain blood volume, which is important in maintaining homeostasis and prevent infection. The sequence of events that occurs in blood clotting is: 1) After an injury collagen fibres are exposed to blood. 2) Platelets stick to the fibres and make other platelets sticky, forming a platelet plug sealing the wound. 3) Clotting factors are released and combine with calcium ions in the blood catalysing a series of reactions: Thromboplastin which converts Prothrombin ► Thrombin which converts fibrinogen ►fibrin. Fibrin is an insoluble network of fibres which traps blood cells, causes blood to coagulate and produces a more permanent seal for the wound. When the fibres dry they form a crusty scab which falls off when the tissue underneath heals properly.

SECOND LINE OF DEFENCE INFLAMMATION Inflammation causes the following changes: Nearby arterioles dilate allowing more blood to reach the affected area Increased blood flow allows a greater number of platelets, macrophages, mast cells and additional substances such as in the blood such as complement and antibodies can reach an affected area. Blood vessels become more permeable which allows response agents to leave the bloodstream and move into the damaged tissue. Mast cells release histamines which cause the “weal and flare” reaction (seen as white swollen tissue)

SECOND LINE OF DEFENCE INFLAMMATION

THIRD LEVEL OF DEFENCE The third level of defence is acquired, specific and adaptive. It is produced by the lymphocytes – T cells and B cells. T cells are responsible for T mediated immunity. They respond to antigen fragments presented to them by macrophages or infected cells. There are several types of T cells including Helper T cells, Delayed hypersensitivity T cells, Suppressor T cells and Cytotoxic (natural killer) T cells. B cells are responsible for antibody mediated immunity and memory of the antigen. B cells are able to recognise and bind to antigens. Immature B cells can differentiate into Memory cells or Plasma cells.

LYMPHATIC SYSTEM Fluid that leaks from the capillaries and surrounds the tissues is called tissue fluid. It supplies nutrients and oxygen to the tissues and removes wastes. Some tissue fluid returns to the blood stream directly but some returns through the lymphatic system and this fluid is called lymph. It is compromised of vessels and lymph nodes. The vessels are separate from the circulatory system, but return fluids and proteins into the blood. Lymph vessels have valves preventing the backflow of lymph fluid. Lymph fluid is filtered by the lymph nodes which swell when infected as lymph cells are reproducing rapidly. Important components of the lymphatic system include: tonsils, thymus gland, spleen and bone marrow. LYMPHOCYTE PRODUCTION Stem cells are produced in the bone marrow after birth (liver in a foetus) which can differentiate into B cells and T cells. B cells mature in the bone marrow and then migrate to lymphatic organs. Immature T cells migrate to the thymus gland, mature there and then migrate to the lymphatic organs.

THIRD LEVEL OF DEFENCE HELPER T CELLS Although they cannot act directly, T helper cells have an import role in the immune system. Helper T cells present antigens to immature B cells enabling them to produce antibodies. They release cytokines which activate and promote the growth of cytotoxic T cells. The cytokines also increase the activity of phagocytic cells. Helper T cells and AIDS Helper T cells are amongst the cells most targeted by the AIDS virus, which then has an impact on the bodies ability to secret antibodies.

THIRD LEVEL OF DEFENCE NATURAL KILLER (CYTOTOXIC) T CELLS NK cells act directly against other cells. NK cells produce proteins such as perforin and proteases When they near a cell that is identified as non-self, perforin forms pores in the cell membrane of the target cell through which the proteases can enter, inducing apoptosis. NK cells also target tumour cells and cells infected by viruses. NK cells are activated in response to interferon or cytokines produced by macrophages. The activity of NK cells is regulated by the presence of 2 surface receptors, 1 is an initiation receptor which turns the NK cell on and the other is an inhibition receptor which turns the NK cell off. The inhibition receptor binds to the MHC marker on the cells surface. When both receptors are bound, the NK cell is turned off.

THIRD LEVEL OF DEFENCE SUPPRESSOR T CELLS Plays a regulatory role in the immune system. When all of the antigens have been removed from the organism suppressor T cells turn the immune response off. Failure of these cells to work effectively can lead to the occurrence of autoimmune diseases.

THIRD LEVEL OF DEFENCE ANTIBODY MEDIATED IMMUNITY An immature B cell will form clones if it comes into contact with a complementary shaped antigen. This is called the clonal selection theory. The clones are mostly plasma cells for immediate use and some memory cells for use in the future. The sequence of events is as follows: 1) A substance or cell with a foreign antigen invades the body 2) Macrophages engulf the antigen, display it on their surface and travel to the lymph nodes. 3) The antigen is presented to T helper cells which present the antigen to B cells. 4) B cells reproduce by mitosis forming a clone of identical B cells, most become plasma cells that produce antibodies and some become memory cells which remain in the lymph node. Plasma cells produce antibodies which bind to and inactivate the antigen. These cells are short lived but produce antibodies at a great rate. Memory cells are long lived and can rapidly differentiate if the same antigen is encountered again.

ANTIBODIES Antibodies are produced in response to foreign antigens. TYPES OF ANTIBODIES There are 5 main classes of antibodies: IgG – circulating antibodies IgM – produced early in the infection response IgA – found in external secretions IgD – located on the surface of B cells. IgE – involved in hypersensitivity (allergic) reactions. Antibodies are specific as they only bind to their complementary antigen forming an antigen/antibody complex. This reaction occurs at the binding site of the antibody. B Plasma cells are able to make several thousand antibody molecules every second. Antibodies have several modes of action

ANTIBODIES COMPONENTS OF ANTIBODIES Antibodies have 3 main components. Constant region (long chain): This region is the same for all antibodies of the same class Hinge region: This region connects the light and heavy chains. It also allows the chains to open and close. Variable region (short chain): this is the area where the antigen binds to. Each antibody can bind to 2 antigens of the same type (not 2 different antigens)

THIRD LEVEL OF DEFENCE ANTIBODY MEDIATED IMMUNITY

THIRD LEVEL OF DEFENCE PRIMARY AND SUBSEQUENT RESPONSES The primary response is the response that occurs the first time an antigen is encountered. It will be comparatively short lived and weak and acts to prime the immune system Subsequent responses will be stronger and faster as the immune system is already able to recognise the antigen. GRAPHING PRIMARY AND SUBSEQUENT RESPONSES The differences between primary and secondary responses is shown on a graph which should include the following information. 1) The peak of the secondary response is much higher than that of the primary response. 2) The positive slope of the secondary response section is steeper than that of the primary response. 3) The negative slope of the primary response is much steeper than that of the secondary response

ACTION OF ANTIBODIES Antibodies have several modes of action NEUTRALISATION Antibodies are released into the blood stream and carried to the area of infection They will be complementary (the right shape) to bind with the same type of antigen as the one that caused the stimulation of the B cell in the first place. The better the fit, the stronger the subsequent immune response will be. The antibody binds to and neutralises (inactivates) the antigen. CAUSING CLUMPING By combining with the antigen, the antibody labels the pathogen (which the antigen is attached to) as foreign. Often several antibodies combine with several antigens so that a complex mass of foreign cells is formed. This action means that the antigens become clumped together make them more vulnerable to phagocytes.

ACTION OF ANTIBODIES COMPLEMENT ACTIVATION Antibodies bind to complement, activating it. As the antibody is bound to an antigen on the surface of a foreign cell (e.g. bacteria), the antibody “tags” the bacteria when it is stuck to it, Making it more easily recognisable to phagocytes. PRECIPITATION Antibodies bind to soluble antigens, causing them to precipitate out of a solution or agglutinate. Antibodies can be used in this fashion to detect the presence of specific antigens.

AUTOIMMUNITY Autoimmune conditions are those where an individuals immune system attacks their own cells damaging body tissues. These conditions occur when the self recognition system breaks down. Examples of these conditions include Polio Multiple sclerosis Rheumatoid arthritis

MONOCLONAL ANTIBODIES Monoclonal antibodies are all descended from a single immortalised hybridoma cell. Hybridomas are produced by fusing antibody producing B cells and immortalised tumour cells. The process is as follows: A mouse is injected with an antigen which stimulates the production of B cells that will produce antibodies for the antigen. B cells and tumour cells (which are immortalised) are cultured. The B cells and tumour cells are fused together producing hybridoma cells with the properties of both. Assays are performed on the hybridoma cells and the ones producing the most antibodies are selected. These hybridoma cells are grown, each is a clone of the original which produces antibodies to the original antigen.

HYPERSENSITIVITY Hypersensitivity reactions are also called allergic reactions. They are an over reaction of the immune system to a comparatively harmless foreign pathogen or substance. These antigens are called allergens. When an allergen (e.g. pollen, animal fur etc.) enters the body, the immune system recognises them as foreign and B plasma cells produce IgE antibodies. The IgE antibodies coat the surface of mast cells (white blood cells lining the respiratory and digestive tracts) sensitising the body to the allergen. When the allergen is encountered a second time it binds to the antibodies on the mast cells and stimulates them to release histamine. Histamine causes swelling and inflammation.

ACTIVE IMMUNITY Active immunity involves exposure to an antigen. As a result the body produces antibodies and retains a memory of the antigen in case of future reinfection. Active immunity can be naturally acquired by normal exposure to a pathogen. Active immunity can be artificially acquired by vaccination. This provides the body with primary exposure to a pathogen and allows a stronger and faster response if the disease causing pathogen is encountered in the future.

PASSIVE IMMUNITY Passive immunity is the provision of antibodies from another organism e.g. antivenin. It is not good for the long term as the antibodies will be identified as foreign and removed from the patient's body, also there has been no cellular response, so no memory will be retained. Naturally acquired passive immunity The most common example of this is that there are antibodies present in breast milk which provides young babies with a source of immunity until their own immune system develops. Artificially acquired passive immunity This involves vaccination, but the vaccine consists of antibodies rather than antigens. This method is used when time is critical as it is not necessary to wait for clonal expansion to occur e.g. if you are bitten by a highly venomous snake you could die before your body is able to make antibodies. Antibodies used in vaccines are frequently monoclonal antibodies

VACCINES There are several types of vaccines, vaccines may be either antigens or antibodies. SUBUNIT VACCINES These are vaccines that contain an antigenic fragment of a pathogen. The advantage with this type of vaccine is that there is no chance of them replicating or mutating. Many of these vaccines also contain adjuvants which are substances that provoke an inflammatory response, attracting more white blood cells to the vaccination site and therefore increasing the level of immune response. WHOLE AGENT VACCINES These are vaccines that contain whole micro-organisms. In some cases the micro-organism has been inactivated by heat or chemicals while in other cases the micro-organism has been attenuated (weakened, with the virulence factors removed). HERD IMMUNITY Some people believe that vaccines have adverse or unknown side effects, which are more significant than the benefits conferred by being vaccinated. As a result they may choose not to have their children vaccinated. However, since most of the population is vaccinated against a range of diseases, this makes it less likely that a person who has not been vaccinated will be exposed to conditions where they will get the disease. This gives them some benefit of vaccination programs without actually being vaccinated. This is what is known as herd immunity.

EXPERIMENTAL DESIGN FACTORS There are a number of factors that need to be considered when designing an experiment. It is essential there is only 1 variable, if there is more than 1 variable it cannot be determined which variable was responsible for a result. As an example if plants are being used for an experiment they should all come from the same parent plant, have the same amount of water, same amount of soil etc. There should be a control group. This is used as a baseline for comparison to determine the amount of response or reaction e.g. if you are testing a drug, a placebo should be used as a control and there should be a better response from those taking the drug compared to those taking the placebo. The sample size should be appropriate e.g. it would not be appropriate to experiment on 1 organism only, there should be a minimum of 5 within each group but more would be better. Sometimes standards are used when it is not possible to determine a chemical concentration directly. Standards contain known concentrations of substances and the response to the unknown level can be compared to that of the standard in order to determine the concentration of the unknown sample.

QUESTION TYPES COMPARE Be aware that this type of question may either use the word “compare” or it may just imply a comparison is needed. All conditions referred to in the question must be mentioned in the answer Sample question Molecule B is a large, lipid soluble molecule, molecule A is a smaller lipid soluble molecule. Explain Which molecule will diffuse faster across the plasma membrane explain? Incorrect answer: molecule A will diffuse faster because it is smaller. Correct answer: Both molecules are lipid soluble, but molecule A will diffuse faster than molecule B due to the fact that molecule A is smaller than molecule B and small molecules diffuse more rapidly than larger molecules. DEFINE A brief answer stating what a particular term means. No examples are necessary – this uses time without adding anything of value to your answer Sample Question Define Homeostasis Homeostasis is the maintenance of a relatively stable internal environment in the face of change.

QUESTION TYPES DEFINE AND PROVIDE AN EXAMPLE Write a brief definition and provide an appropriate example. DESCRIBE The response must contain a description using provided information e.g. the level of enzyme activity increases from 5 arbitrary units to 10 arbitrary units. EXPLAIN A response to this type of question should explain why something has occurred e.g. increasing the heat in an enzyme catalysed reaction gives the particles more kinetic energy increasing the level of enzyme activity from 5 arbitrary units to 10 arbitrary units. LIST A very brief answer stating a term or piece of key knowledge.

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Unit 3 Biology Study Cards