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Unit 1 - Biology and disease

AQA AS Biology
Unit 1: Biology & Disease Summary Notes

Unit 1 - Biology and disease

Unit 1 - Biology and disease Biochemistry Organisation of matter Matter: anything that occupies space and has mass. All forms of matter are made up of elements. The elements hydrogen, carbon and oxygen make up most of the human body. Atoms: the smallest unit of matter that are unique to a particular element. Molecules: units of two or more atoms bonded together. Protons: positi e particles. !eutrons: neutral particles. "lectrons: negati e particles. Bonding Ionic bonding: An association between # oppositely charged ions. $harged particles %ions& ha e a change in the number of their electrons. !egati e ions gain electrons. Positi e ions lose electrons. Covalent bonding: Atoms share electrons. 'ingle bond ( ) pair shared, eg *#. +ouble bond ( # pairs shared, eg ,#. Triple bond ( - pairs shared, eg !#. Polarity: 'ome co alent molecules are polar. o Atoms of different elements do not exert the same pull. o The net charge is balanced. o "g. water. Hydrogen bonding: ./an +er 0aal1s forces1. An atom of a molecule interacts with another hydrogen atom that is already taking part in a co alent bond. +ue to polarity ( the o erall charge of each molecule is neutral, but the distribution of electrons is une en. 2ndi idually weak. $ollecti ely stabilising.

Unit 1 - Biology and disease

"xamples: o 3etween water molecules. o 3etween water and ammonia. o 3etween water and glucose. o 0ithin +!A ( base pairing.

Polymers and Monomers 3iological molecules such as carbohydrates and proteins are often polymers and are based on a small number of chemical elements. Group Name $arbohydrates Proteins !ucleic acids Carbohydrates General details: *ydrates of carbon. $ontain carbon, hydrogen and oxygen. 7eneral formula $x%*#,&y. - groups: o Monosaccharides ( single sugars. o +isaccharides ( double sugars. o Polysaccharides ( many sugars %more than #&. 8ses: o 'tructural ( cellulose, chitin. o "nergy ( glucose. o 'torage ( glycogen, starch. o 2n nucleic acids ( ribose, deoxyribose. Monosaccharides The basic molecular units %monomers& of which carbohydrates are composed. Polymers Polymer e ample Polysaccharides 'tarch Polypeptides Amylase Polynucleotides +!A Monomers Monosaccharides Amino acids !ucleotides Monomer e ample 45glucose 6eucine Adenosine phosphate

Unit 1 - Biology and disease 7eneral formula $*#,n 7lucose 5 $9*)#,9. *exose sugar. Main substrate for respiration. Transported in mammalian blood. Monomer for starch, glycogen and cellulose. The structure of 45glucose:

45glucose link together by glycosidic bonds This is a condensation reaction 5 2n ol es the loss of a water molecule. 2t :oins # sugars by an oxygen.

*ydrolysis reaction ( required to split the glycosidic bond. This requires the use of a water molecule to reform the hydroxyl groups on each of the two new sugars where the bond is split.

!isaccharides Maltose is formed by condensation of two 45glucose molecules Maltose has an 4 ),; glycosidic bond ( between carbons ) and ;. Maltose is a reducing sugar. 'ucrose is formed by condensation of glucose and fructose. 'ucrose is a non5reducing sugar. 6actose is formed by condensation of glucose and galactose.

Unit 1 - Biology and disease 6actose is a reducing sugar.

Polysaccharides Polysaccharide < .many sugars1. Polymers of monosaccharides. =ormed by condensation reactions. /ariable numbers of monosaccharides. 3ranched or unbranched chains. May be folded. 2nsoluble due to si>e. "xert no osmotic influence. +o not diffuse easily. 'plit into disaccharides and monosaccharides by hydrolysis. "tarch =ound in most parts of a plant in starch grains. =ood reser e from excess glucose. =ood supply in seeds for germination. 2mportant food supply in animals. Made of 4 glucose. $ompact for storage. # constituent structures: o Amylose: Approx #?@ of starch. 4 ),; glycosidic bonds. 'piral structure held together by hydrogen bonds. o Amylopectin: Approx A?B of starch. 4 ),; and 4 ),9 bonds. 3ranched chains.

Unit 1 - Biology and disease

Unit 1 - Biology and disease Proteins Polymers of amino acids. 6arge molecular mass. 0ide ariety of functions. $arbon, hydrogen, oxygen and nitrogen. 8sually sulphur as well. "ach species has a particular range of proteins. +etermined by the genetic code. Make up two5thirds of total dry mass of cell Make up )A@ of human body %second only to water& Most complex and di erse group of biological compounds

#ange of $unctions: =unction 'tructure "n>ymes Transport Acti e transport Muscles *ormones Antibodies "xamples $ollagen %bone, cartilage, tendon&, Ceratin %hair& Actin %muscle& Amylase, pepsin, catalase *aemoglobin %oxygen& 'odium ( Potassium pumps in cell membranes Myosin and actin 2nsulin, glucagon 2mmunoglobulins

%mino %cids Proteins are made up of amino acid chains. The general structure of an amino acid is: D 2 *#! ( $ ( $,,* 2 * The central carbon has ; groups attached to it: o a hydrogen atom o a basic amino group o an acidic carboxyl group o a ariable .D1 group %or side chain& There are #? naturally occurring amino acids in li ing organisms. *alf of these can be created in the body ( non5essential amino acids. The other half must be consume in the diet ( essential amino acids.

Peptide Bond 0hen # amino acids :oin together they form a dipeptide using a peptide bond or link.

Unit 1 - Biology and disease This is a condensation reaction.

To break this bond requires a hydrolysis reaction. This requires the use of a water molecule to reform the amino and caboxyl groups on each of the two new amino acids where the bond is split.

Polypeptides Many amino acids make up a polypeptide chain. Amino acid polymerisation for polypeptides is part of protein synthesis. The sequence of amino acids in a chain is determined by the sequence of the genetic code in +!A. Protein structure Protein structure can be broken down into ; le els: Primary structure The primary structure refers to the sequence of amino acids +etermines rest of protein structure "econdary structure Amino acid chains fold and mo e to take up a particular shape Amino acids find the most stable hydrogen bonds Most common secondary structures are 45helix and the E5sheet %lpha &heli : A regular spiral *eld together by hydrogen bonds /ery stable =orms part of most proteins

Unit 1 - Biology and disease Beta'pleated sheet: A >ig5>ag formation $onsisting of two or more chains Dunning parallel to each other 6inked by hydrogen bonds.

(ertiary structure , erall three5dimensional shape formed by the folding up of a whole polypeptide chain. " ery protein has a unique tertiary structure, which is responsible for its properties and function. Tertiary structure held together by bonds between the D groups of the amino acids. There are - different types: o hydrogen bonds ( weak o ionic bonds ( between oppositely charged D groups, quite strong o disulphide bridges ( strong co alent bonds between sulphur on cysteine D groups. )uarternary structure =inal three5dimensional structure This is how different polypeptide chains are :oined together. Also includes non5protein prosthetic groups which are present in some proteins. "g, haemoglobin is a globular protein with ; polypeptide chains, each with a haem group %containing an atom of iron&. $ibrous proteins: 6ong supercoiled chains. 'econdary structure is important. Many polypeptide chains run parallel, cross5linked with bonds, eg disulphide bridges. 'table, and structurally strong. "xamples: o Ceratin ( skin, hair, bones.

Unit 1 - Biology and disease o $ollagen ( skin, bones and tendons. o =ibrin ( blood clots Globular Proteins: More spherical. 'maller ones are soluble. 'pecific shape. Tertiary and quaternary structure forms specific shape. ,ften part of the protein has a complementary shape to another specific molecule. "xamples: o *ormones ( eg insulin and glucagon attach to receptors on cell membranes o "n>ymes ( acti e site specific to substrate o Antibodies ( complementary to specific antigens o *aemoglobin *ipids General details: 6arge, aried group of organic compounds. $ontain carbon, hydrogen and oxygen. 2nsoluble in water. +issol e in organic sol ents, eg alcohol. - main types: o Triglycerides. o Phospholipids. o 'teroids. (he molecule # main sections:

o 7lycerol: An alcohol containing - carbon atoms. "ach carbon has a hydroxyl group. o =atty acids:

Unit 1 - Biology and disease These determine the characterisitics of the lipid. They contain a carboxyl group %5$,,*&. This is attached to a ariable D group 5 a hydrocarbon chain. # groups of fatty acids: 'aturated: o !o double bonds between carbon atoms. o "g butyric acid found in butter. o "g palmitic acid found in animal and egetable fats. o A high proportion in the diet may increase risk of heart disease. 8nsaturated: o ,n or more double bonds, o "g linoleic acid ( linseed oil. o "g oleic acid ( found in oli e oil. o Polyunusaturated ha e # or more. o Monounsaturated ha e one.

Bonding: =atty acids bond to glycerol by an ester linkage. =ormation is a condensation reaction. *ydrolysis reactions break the bond. An oxygen atom :oins a carbon on the glycerol with carbon on the carboxyl end of the fatty acid. (riglycerides - fatty acid chains. +iffer according to type and length of chains. o Oils: Delati ely short fatty acids or unsaturated fatty acids. Tend to be liquid at room temperature.

Unit 1 - Biology and disease o $ats: 6onger fatty acid chains or saturated fatty acids. More likely to be solid at room temperature. Main use is as an energy source. $an be broken down into glucose %gluconeogenesis& and used in respiration.

+ses: Animal energy stores. Twice as much energy per gram as carbohydrates. 2deal for the low mass required for locomotion. 2nsulation: $onduct heat slowly. Protection of ital organs. 0aterproofing fur and feathers with oil secretions. Phospholipids ,ne fatty acid group is replaced by a phosphate group. The fatty acid chains are hydrophobic. The phosphate group and glycerol part are hydrophilic. Main role is in cell membranes.

Unit 1 - Biology and disease Microscopes +nits of measure ) meter < ),??? mm < ),???,??? Fm < ),???,???,??? nm ) millimeter %mm& < )G)??? m ) micrometer %m& < )G),???,??? m < )G)??? mm ) nanometer %nm& < )G),???,???,??? m < )G)???,??? mm < )G)??? m , amples: =rog egg < )mm *uman egg < )?? m Most animal cell < )? to -? m Most plant cells < )? to )?? m Prokaryotic cells < ) m Mitochondria < ?.H to ) m $hloroplast < H m !ucleus < I m /irus < )? to -?? nm Dibosome < -? nm Magnification: The ratio of how much bigger a sample appears when iewed under the microscope than its actual si>e. The resolution limits how much detail can be seen. Calculating magnification from photographs: Magnification < length in photograph Deal length $alculating real length from photographs: Deal length < 6ength in photograph Magnification !3 for both, con ert the length in the photograph into the same units that are used for the specimen. This is usually in micrometers. #esolution The smallest separation at which two separate ob:ects can be distinguished %or resol ed&. The greater the resol ing power, the more detail can be seen. The resolution of an image is limited by the wa elength of radiation used to iew the sample. 0hen ob:ects in the specimen are smaller than the wa elength of the radiation being used, they do not interrupt the wa es, and so are not detected. The resol ing power of a light microscope is limited by the wa elength of light %;??59??nm for isible light&.

Unit 1 - Biology and disease ,b:ects closer than #??nm will still only be seen as one point, no matter how great the magnification. "lectrons ha e a much lower wa elength than light. A beam of electrons has an effecti e wa elength of less than ) nm. "lectron microscopes ha e higher resolution. *ight Microscopy

Most widely used form of microscopy. 'pecimens are illuminated with light =ocussed using glass lenses. Modern microscopes 5 $ompound microscopes use se eral lenses to obtain high magnification. 6ight microscopy has a resolution of about #?? nm: /iew cells, and large organelles but not the details of organelles 'pecimens can be li ing or dead. 'pecimens often need to be stained with a coloured dye to make them isible. Many different stains are a ailable that stain specific parts of the cell such as +!A, lipids, cytoskeleton, etc.

,lectron Microscopy +e eloped in )J-?s. 8ses a beam of electrons to KilluminateK the specimen. "lectrons beha e like wa es. Produced using a hot wire =ocussed using electromagnets +etected using a phosphor screen or photographic film A beam of electrons has an effecti e wa elength of less than ) nm. Desol ing power is enough to iew small sub5cellular ultrastructure. Mitochondria, "D and membranes can be seen in detail.

Unit 1 - Biology and disease Problems 'pecimens must be fixed in plastic or co ered in hea y metals. /iewed in a acuum. Therefore, specimens must be dead. The electron beam can damage specimens. Must be stained with an electron5dense chemical, usually hea y metals like osmium, lead or gold. People argue that many obser ed structures could be artefacts 5 due to the preparation process and not real. (ransmission electron microscope .(,M/

0orks much like a light microscope. A beam of electrons is passed through a thin specimen. "lectrons are focussed to form an image on a fluorescent screen or on film. Most common form of electron microscope. 3est resolution ( ?.# nm $reates a #5dimensional flat image.

(he scanning electron microscope .",M/

Unit 1 - Biology and disease

A fine beam of electron is scanned onto a specimen. "lectrons are scattered by the surface, due to the hea y metal co ering. A fluorescent screen or film is used to detect the reflected electrons. This has poorer resolution ( )? nm 7i es -5dimentional images of surfaces. The electrons do not ha e to pass through the sample in order to form the image. 6arger, thicker structures can be seen under the '"M. "eparating Cell Components

Cell $ractionation The separation of different parts and organelles of a cell. Delati e proportions of each organelle can be disco ered. 3iochemical contents of each organelle can be in estigated. Process: ). Place tissue %e.g. li er, heart, leaf, etc& in ice5cold isotonic buffer. $old to stop en>yme reactions. 2sotonic to stop osmosis. 3uffer to stop p* changes. #. 7rind tissue in a blender to break open cells (homogenation. -. =ilter to remo e insoluble tissue e.g. fat, connecti e tissue, plant cell walls, etc. This filtrate is now called a cell'free e tract!ifferential Centrifugation A centrifuge is a piece of equipment, dri en by a motor, that puts an ob:ect in rotation around a fixed axis, applying a force that is perpendicular to the axis. The centrifuge works using the sedimentation principle, where the centripetal acceleration is used to separate substances of greater and lesser density. ' edberg unit ( used to compare si>es of ribosomes ( a measure of their density.

Unit 1 - Biology and disease Process: ). $entrifuge filtrate at low speed and remo e pellet. #. Depeat at increasingly higher speeds. -. "ach pellet remo ed contains structures of lower density. !ensity gradient centrifugation . The cell5free extract is centrifuged in a dense solution "g sucrose or caesium chloride The fractions separate out into layers with the densest fractions near the bottom of the tube. *ea iest 6ightest !uclei Mitochondria 6ysosomes Dibosomes

Unit 1 - Biology and disease

Unit 1 - Biology and disease Cells $ell < the smallest unit of life. All li ing organisms are made of cells. There are unicellular organisms that consist of one cell: o 3acteria o 3lue5green bacteria o Proto>oa o Least These indi idual cells must carry out all of the essential life proceses ,ther organisms are made of many cells. These are multicellular organisms: o Animals o Plants o Mushrooms o 'eaweed 2n these the life processes can be delegated to different organs and tissues.

(0o main divisions of cells Prokaryotic cells: o 3acteria o 3lue5green bacteria "ukaryotic cells o Animals o Plants o =ungi o Protoctista Pro < before "u < true Caryo < nucleus Pro1aryotic Cells "xample: o $holera ( Vibrio cholerae Prokaryote < .before the nucleus1 'imple cells containing no membrane bound organelles $onsidered to be the earliest form of life on "arth.

Unit 1 - Biology and disease

'tructure $ell wall

Plasma membrane

+!A

Dibosomes =lagella

Plasmids

=unction Pro ide shape Protect against rupture by osmosis 'ome protection against other organisms Digid Made of peptidoglycans ( polymers of sugars and amino acids Phospholipids and proteins Proteins include en>ymes for metabolic processes "g respiration, nucleic acid synthesis %in all& and photosynthesis %in some& =luid mosaic 3arrier for selecti e exchange of nutrients and waste products Mo ement by diffusion %including osmosis& and acti e transport 'ingular, circular chromosome +!A helix 2n cytoplasm, not nucleus Attached to plasma membrane "g ".coli ; x )?9 base pairs %A, $, T and 7&, about ;??? genes 'maller than in eukaryotic cells 'ite of protein synthesis *ollow cylinder Made of rigid protein strands %flagellin& Arise from basal bodies in plasma membrane in some bacteria Dotate from base like a rotor blade 3ring about mo ement Additional hereditary material 'mall rings of +!A, )? ( -? genes 2n cytoplasm of some, not all, bacteria "g antibiotic resistance

Unit 1 - Biology and disease $an be transferred through con:ugation tubes "xploited as ectors in genetic engineering Tangled mat of polysaccharide fibres 'limy physical barrier ,uter protecti e layer in some bacteria Protects against chemicals and dessication Protects against attack by phagocytic cells *elps bacteria to form colonies

$apsule

,u1aryotic Cells

"ukaryote < .true nucleus1 These cells contain organelles

Cell membrane Thin layer found round the outside of all cells. Made of phospholipids and proteins. $ontrols the mo ement of materials in and out of cell. Microvilli 'mall finger5like extensions of the cell membrane found in certain cells eg, epithelial cells of the intestine and kidney. 2ncrease surface area. Cytoplasm 0atery solution within cell membrane. $ontains: o "n>ymes for metabolic reactions o 'ugars, salts, amino acids in solution.

Unit 1 - Biology and disease Organelles Membranous sacs. $ompartmentalise portions of the cytoplasm. 2ncrease the surface area for reactions. Allow metabolic reactions to be sequenced. 2solate potentially harmful chemicals. Nucleus The largest organelle %)?Mm diameter&. $ontrols cell1s acti ities. 'tore genetic material ( chromosomes which are made of +!A. 'pherical 'urrounded by nuclear en elope: o # membranes filled with fluid !uclear pores enable mD!A to enter the cytoplasm. 2nterior is nucleoplasm which is full of chromatin %+!AGprotein&. !ucleolus is a dark region of chromatin, site of D!A transcription. Mitochondrion o 'ite of aerobic respiration in all eukaryotic cells. o #.H to H micrometers long. o 'pherical or rod shaped o +ouble membrane o 2nner membrane folded into cristae 5 large surface area. o 2nternal space is the matrix, a solution of metabolites and en>ymes. o Also contain loops of +!A. o ATP synthase %stalked particles& are on the inner membrane. o 'ite of latter stages of respiration. o Metabolically acti e cells contain numerous mitochondria. o !umber of cristae also increases with increased acti ity. #ibosomes o 'mallest and most abundant .organelles1 o !ot membranous o 'ite of protein synthesis o Made in nucleolus o Made of protein and D!A o =ound either in cytoplasm or attached to the rough endoplasmic reticulum %D"D& o 6arger type %A?'& o ,ften found in groups called polysomes ,ndoplasmic reticulum .,#/ o An elaborate system of membranes. o =orms part of the cytoplasmic skeleton. o "xtends from the nuclear membrane. o 'eries of flattened stacks called cisternae.

Unit 1 - Biology and disease o "nables substances to be synthesised and transported. o #ough ,# .#,#/ o 'tudded with ribosomes, gi es it rough appearance o Polypeptides synthesised by ribosomes are passed into it. o Pass proteins to 7olgi body for further processing. o "mooth ,# %'"D& o !o ribosomes. o 2n ol ed in synthesising and transporting steroids. 2esicles o 'mall membrane bound organelles. o +eli er substance around cell. o Take substances: o =rom "D to 7olgi o =rom 7olgi to cytoplasm 5 lysosomes o =rom 7olgi to cell membrane for exocytosis ( secretory esicles o "g release of digesti e en>ymes. Golgi body .Golgi apparatus/ o 'eries of flattened membrane sacs. o 'imilar structure to "D. o More compact and cur ed. o Transports proteins from the D"D to the cell membrane o /esicles of D"D fuse with the 7olgi on one side o $ontents of the esicles enter the 7olgi o 'teroids may be modified. o Proteins may acquire tertiaryGquaternary structure. o ,ther groups may be added. o /esicles bud off the other side and mo e into the cytoplasm. *ysosomes o A type of esicle. o $ontain en>ymes. o 8sed to breakdown unwanted toxins or organelles to recycle materials. o "g used in phagocytosis. "ummary of differences bet0een pro1aryotic and eu1aryotic cells Prokaryotic cells "xtremely small %N)?Mm& Always unicellular !o nucleus or membrane5bound organelles +!A is circular, without proteins 'mall ribosomes %I?'& "ukaryotic cells 6arger cells %)?5)H?Mm& ,ften multicellular !ucleus and other membrane5bound organelles +!A is linear and with protein form chromatin 6arge ribosomes %A?'&

Unit 1 - Biology and disease $ell wall always present $ell di ision by binary fission $ell wall only in plant and fungi $ell di ision by mitosis or meiosis , change across cell membranes Cell membranes 'urround all cells 5 also known as cell surface membrane or plasmalemma. Also surround most cell organelles eg mitochondria, nucleus, 7olgi, lysosomes, "D Also form structures inside organelles eg cristae in mitochondria. "tructure 2ts structure relies on a phospholipid bilayer Phospholipids are arranged as a double layer. This is about I5)?nm thick. *ydrophilic phosphate and glycerol heads are orientated outwards. *ydrophobic fatty acid chains orientate inwards. Made up almost entirely of phospholipids and proteins with a small amount of carbohydrates and cholesterol. Accepted theory is the 3$luid Mosaic4 model. =luid ( proteins and other embedded molecules can mo e laterally %sideways&. Mosaic ( appears as such from surface iew due to the close fitting arrangement of the phospholids and the integral proteins.

Membrane proteins $unctions $reate pores through which water and water5soluble chemicals can pass Act as carriers in acti e transport and facilitated diffusion =orm receptor sites for hormones

Unit 1 - Biology and disease 2mportant for cell recognition

(ypes $hannel protein o $reate pores through which water and water5soluble chemicals can diffuse through $arrier proteins o 2n ol ed in facilitated diffusion and acti e transport 7lycoproteinO o A protein attached to polysaccharide chain o *elps cells to recognise each other Other constituents of the cell membrane 7lycolipids o Polysaccharide chain attached to a lipid %in place of the phosphate group& o Also help recognition $holesterol stabilises the cell membrane. Movement across membranes o All li ing cells are surrounded by water. o "xamples: o Plant cells ha e a cellulose cell wall but inside this there is a tissue fluid that bathes the cell membrane too. o 2n mammals their bodies are co ered in a layer of dead cells, below this the cells are li ing and bathed in tissue fluid. o Therefore all transport in and out of cells happens in solution. o This transport can happen by arious mechanisms. !iffusion o +efinition: The mo ement of particles within a gas or liquid from a region of high concentration to a region of lower concentration until an equilibrium is reached. o All particles in liquids and gases are in constant random motion o 2f there is a difference in concentration between parts of a gas or liquid, these random mo ements carry particles from the area of high concentration to the area of lower concentration. o The difference in concentration between two areas is the concentration gradient. o The particles mo e down this gradient. o This continues until the particles become e enly dispersed ( dynamic equilibrium. o +iffusion is the main process by which substances mo e o er short distances and is essential for exchange to occur in all cells. o +iffusion is a passi e process < requires no energy "i5e and nature of diffusing particle o =at5soluble molecules can pass through lipid bilayer eg alcohol and steroids o 'mall molecules such as oxygen and carbon dioxide can diffuse through small pores between the phospholipids

Unit 1 - Biology and disease o 6arger water5soluble molecules such as glucose and amino acids must pass through protein poreso /ery large molecules cannot diffuse into cells at all. $actors affecting the rate of diffusion o 'urface area: o The greater the surface area the greater the rate of diffusion. o Micro illi increase the surface area in some cells. o +istance: o +etermined by the thickness of the membrane. o The greater the distance the slower the rate of diffusion. o $oncentration gradient: o The greater the concentration gradient the greater the rate of diffusion. o +iffusion is more efficient if the gradient can be maintained. o This is done by transporting the substance away once diffused or combining with other chemicals so it cannot diffuse back. =ick1s 6aw: Date of +iffusion is proportional to: 'urface area x concentration difference distance $acilitated diffusion o 'ome substances that may not normally diffuse across a membrane are facilitated %helped& by proteins in the membrane. o 6ike diffusion this process is down a concentration gradient and is passi e ( there is no energy input. o # types: ). $arrier proteins: The molecule binds to protein Protein changes shape Molecule ends up facing the other side of the membrane and is released. #. $hannel proteins: These are proteins that cross the membrane with a channel running throughout them. 2n some cases, protein channels may open or close to signals: "g /oltage gated channels in neurones. 8sed in transmission of ner e impulses. 2n both cases, these proteins are specific to the molecule that passes through them. This means that cells can be selecti e in terms of the type of molecule that passes through their cell membrane.

Unit 1 - Biology and disease

Unit 1 - Biology and disease Osmosis o +efinition: The net mo ement of water molecules from a region of their higher concentration to a region of their lower concentration, through a partially permeable membrane. , planation o *ow does water cross the cell membraneP o $hannel proteins ( permanently open which allow unrestricted mo ement of water at all times. o 6ipid pores ( although the lipid bilayer is theoretically impermeable to water, water is able to pass through tiny temporary holes that open up as the lipids mo e around o Any molecule dissol ed in water is known as a soluteo 0ater molecules are polar. o 'olute molecules are attracted to the water molecules, resulting in their being less free5 mo ing water molecules. o 'olute molecules also impede %get in the way of& the mo ement of water molecules. o Therefore the presence of solute molecules reduces the opportunities for water to cross the cell membrane. o ,smosis is affected by the relati e concentrations of solutes in the two fluids either side of a membrane. 6ater Potential o A measure of the free kinetic energy of water molecules. o 2n an equation, the symbol for water potential < Q %7reek letter .psi1& o 8nits for measurement < kPa %kilopascals& pressure units. o The higher the water potential, the greater the tendency of water molecules to lea e a solution by osmosis. o 2n standard conditions %#HR$ and )??kPa& pure water has a water potential of >ero.% Q< ?& o The addition of solute molecules lowers this alue. o More concentrated solution < more negati e Q o 0ater diffuses from less negati e Q to more negati e Q o "g. from 5)??kPa to (#??kPa o Better definition:,smosis is the net mo ement of water molecules from a region of higher %less negati e& water potential to a region of lower %more negati e& water potential, across a partially permeable membrane. Osmosis in animal cells: 2n ery dilute solutions, water enters animal cells. They swell up and burst ( this is called cell lysis. 2n concentrated solutions, water lea es the cell by osmosis, and the cell shrinks. 2n either case the cell will die. Therefore, animal cells must always be bathed in an isotonic solution 5 a solution with the same solute concentration as the cytoplasm This is regulated by homeostasis, particularly in ol ing the kidneys. The exact amount of water and salt remo ed from our blood by our kidneys is under the control of a part of the brain called the hypothalamus.

Unit 1 - Biology and disease osmoregulation- ' The process of regulating the amounts of water and mineral salts in the blood .

Osmosis in plant cells: Plant cells always ha e a strong cell wall surrounding them. 0hen the take up water by osmosis they start to swell, but the cell wall pre ents them from bursting. Plant cells become KturgidK when they are put in dilute solutions. Turgid means swollen and hard. The pressure inside the cell rises. This pressure works against osmosis. " entually the internal pressure of the cell is so high that no more water can enter the cell. Turgidity is ery important to plants because this is what make the green parts of the plant Kstand upK into the sunlight. 0hen plant cells are placed in concentrated sugar solutions they lose water by osmosis and they become KflaccidK. 2n this case, plants wilt. The contents of the cells ha e shrunk and pulled away from the cell wall: they are said to be plasmolysed. 0hen plant cells are placed in a solution which isotonic they are in a state between turgidity and flaccidity 5 incipient plasmolysis.

Unit 1 - Biology and disease %ctive transport o o o o The mo ement of substances across a membrane against the concentration gradient. Dequires energy %ATP& 8ses specialised carrier proteins in the membrane. $ells and tissues carrying out acti e transport are characterised by: o Presence of numerous mitochondria. o *igh concentration of ATP o *igh respiratory rate

Process ). ATP is hydrolysed by the carrier protein lea ing phosphate attached. The terminal phosphate group con erts the protein to a high energy molecule. #. The protein readily combines with the substance. -. The protein makes a conformational change which exposes the substance to the other side of the membrane. ;. The phosphate group is lost and protein re erts back to original shape. , o o o o amples of active transport Absorption of amino acids from the gut to the blood Absorption of mineral ions by the roots of plants "xchange of sodium and potassium ions in ner e cells Mo ement of sodium ions out of kidney tubules.

o $ells can manipulate osmosis by acti ely transporting ions to one side of the membrane: o "xamples: Acti e transport of sodium ions in Cidney tubules Acti e uptake of mineral ions by Doot hair cells Acti e uptake of specific ions in the small and large intestines

Unit 1 - Biology and disease !isease Pathogens Pathogen < a disease inducing organism. The host is the affected organism. +isease < an abnormal condition of an organism that impairs bodily functions. Pathogens include bacteria, iruses and fungi. 3acteria: o 3acteria are simple, prokaryotic cells ( structure is co ered later. o They contain no nucleus or membrane bound organelles. o !ot all are pathogenic. o 3acteria can tolerate a wide range of conditions, and multiply rapidly. o They often release toxins too. /iruses: o /iruses are not strictly cells. o They are particles comprising of a protein coat containing genetic material and en>ymes. o All iruses are pathogenic. o They must li e as a parasite by in ading host cells to reproduce ( obligate parasites. =ungi o =ungi are more complex, eukaryotic cells. o They ha e a nucleus and other membrane bound organelles. o !ot all are pathogenic. o =ungi reproduce relati ely slowly, and rarely infect internal tissues. o They tend to infect external epithelium. , amples in syllabus: o $holera o A bacterium o Affects the digesti e system o Deleases toxins o $auses se ere diarrhoea o Tuberculosis o A bacterium o Affects the lungs o 2nfluen>a o A irus o Affects the lungs and trachea. o *ost1s immune system releases chemicals, which cause fe er, muscle aches and fatigue. (o cause a disease7 the pathogen must: ). "nter the body: 7as5exchange system +igesti e system 8rinogenital system

Unit 1 - Biology and disease 'kin

#. $olonise an area of the body: Attachment to the cell membrane, often of epithelial cells. -.Mo e into tissues: 'ecretion of proteolytic en>ymes: o 3reak down basement membrane of epithelial cells. o "nter tissuesGfluids underneath. ;. Multiply: 7eneration time decreases, stimulated by new en ironment Dapid multiplication H. +amage the host1s tissues: 0hen pathogens enter host cells, these cells are often destroyed. 'ome pathogens release toxins: o "xotoxins: 'oluble proteins Deleased into en ironment by the pathogen Tra el in blood "ffect other parts of body "xamples: 3otulinum toxin ( muscle paralysis Tetanus neurotoxin ( muscle paralysis 7angrene toxin ( breaks down cell membranes "nterotoxins 5 affect intestinal epithelium. o "ndotoxins: Part of the pathogen cell membrane 6iberated when the pathogen is destroyed. Desponsible for: 'kin rashes =e er 2ncreased permeability of blood essels, resulting in: o 'e ere drop in blood pressure o $irculatory failure o +eath 9. 'pread ( in asi eness: Pathogens may mo e through lymph essels and blood stream. 6odge in particular tissues. Dapid multiplication. !iseases influenced by lifestyle o 6ifestyle can affect human health.

Unit 1 - Biology and disease o 'pecific risk factors are associated with arious diseases. o "xercise o 'tress o +iet: 'alt =at Malnutrition o 'moking o Alcohol consumption o "xposure to: $ar fumes Pollution $oal dust Dadiation Asbestos o $hanges in lifestyle may also be associated with a reduced risk of contracting these conditions. , amples in syllabus: o Asthma: o $an be cause by numerous allergens eg dust, smoking. o "ffects lung function. o =ibrosis of the lungs: o $an be caused by coal dust. o "ffects lung function o "mphysema o $an be caused by smoking. o "ffects lung function o Atheroma o $an be caused by excessi e fat %6+6s& in the diet o "ffects arteries and blood flow o Aneurysm o 6ocalised swelling of a blood essel. o $an rupture causing internal bleeding and death. o $an be exacerbated by smoking and high cholesterol. o Thrombosis o =ormation of a clot in a blood essel. o 3locks blood flow in or leading to an organ or tissue. o $an be exacerbated by smoking and high cholesterol. o $oronary heart disease %$*+& o =ormation of plaques on the walls of the coronary arteries that supply the muscle of the heart. o $an limit blood flow to the heart muscle. o 2f dislodged, can result in: Myocardial infarction: 3lood supply to the heart muscle is interrupted

Unit 1 - Biology and disease o $an be exacerbated by smoking and high cholesterol. o 6actose intolerance o $an be brought about by reduced exposure to milk in the diet. o Production of lactase decreases with time. o "xposure to other diseases can increase the likelihood of lactose intolerance, eg coeliac disease. !iseases influenced by genetic factors o 'ome diseases occur due to errors in the +!A. o The onset of these may be exacerbated by lifestyle. , amples in syllabus: o $ystic fibrosis o An inherited condition o 7enetic emphysema o An inherited condition o A predisposition to this degenerati e disease. o 'moking will accelerate its onset. o 6actose intolerance o An inherited predisposition to de eloping lactose intolerance. 6hat is ris18 A measure of the probability that damage to health will occur as a result of a gi en ha>ard *owe er, we also need to consider the consequences of the ha>ard. "g More people are exposed to car fumes, but smoking probably has greater ad erse consequences than exposure to car fumes. Disk is measured as a percentage. o ? @ < no harm will occur o )??@ < harm will certainly occur This must be comparati e with another scenario "g not taking exercise s taking exercise. *ow much exercise is takenP This data must be pro ided. Timescale also needs to be pro ided. Cancer A class of diseases in which a group of cells display the traits of: o uncontrolled growth %growth and di ision beyond the normal limits&, o invasion %intrusion on and destruction of ad:acent tissues&, o and sometimes metastasis %spread to other locations in the body ia lymph or blood&. Most cancers form a tumor but some, like leukemia, do not. !early all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. They may be randomly acquired through errors in +!A replication,

Unit 1 - Biology and disease ,r, they may be inherited, and thus present in all cells from birth. There are complex interactions between carcinogens and the host genome. This may explain why only some de elop cancer after exposure to a known carcinogen.

(he lin1 bet0een *ifestyle and Cancer " idence suggests that around half of all cases of cancer diagnosed in the 8C could be a oided if people made changes to their lifestyle. "mo1ing o 'moking tobacco is the greatest risk factor for cancer. o 2t causes more than one in four cancer deaths and has killed six million people o er the last H? years. Body 0eight o 3eing o erweight is known to increase the risk of cancer. Physical activity o 2ndependent of body weight, people with higher le els of physical acti ity ha e a reduced risk of colon and probably breast cancer. !iet o /arious constituents of diet may be increase the chance of contracting cancer o Also, arious constituents of diet may be protecti e against cancer. o "g eating a balanced diet, which contains plenty of fruit and egetables, can help to pre ent cancer. "unlight o "xcessi e exposure to ultra5 iolet radiation is the most important modifiable risk factor for skin cancer. Occupation o $ontact with certain harmful substances in the workplace can cause cancer. o Most known occupational carcinogens are either banned or well regulated within the 8C. o J out of )? people who de elop mesothelioma %a rare type of cancer affecting the lining of the lung and abdomen& ha e had contact with asbestos. Correlations and causal relationships Causal relationships ' a logical relationship between one e ent %called cause& and another e ent %called effect&. There will be a correlation between the cause and the effect. Correlation ( a linear relationship between two ariables, where an increase or decrease in one ariable coincides with an increase or decrease in the other ariable. *owe er, correlation does not imply causation. There may be another ariable that causes both of these ariables to change. , ample: o !umerous studies showed that women who were taking combined hormone replacement therapy %*DT& also had a lower5than5a erage incidence of $*+. o This lead doctors to propose that *DT was protecti e against $*+.

Unit 1 - Biology and disease o *owe er, controlled trials showed that *DT actually caused a small and significant increase in risk of $*+. o De5analysis of the data showed that women undertaking *DT were more likely to be from socio5economic groups with better than a erage diet and exercise regimes. o The two were coincident effects of a common cause, rather than cause and effect. (he lin1 bet0een smo1ing and lung cancer o o o o o o o o o o o o o o o o The incidence of lung cancer is highly correlated with smoking. The link between tobacco and cancer was established more than H? years ago. $orrelations can also be made between smoking and socio5economic backgound. Therefore, there may be other causati e agents. "stimated J?@ of lung cancer deaths are caused by smoking. Among male smokers, the lifetime risk of de eloping lung cancer is )I.#@. Among female smokers, the risk is )).9@. This risk is significantly lower in non5smokers: o ).-@ in men and ).;@ in women. $igarette smoke contains o er 9? known carcinogens Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. The length of time a person smokes as well as the amount smoked increases the personSs chance of de eloping lung cancer. 2f a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually remo ed. There is e idence that lung cancer in ne er5smokers has a better prognosis than in smokers. Patients who smoke at the time of diagnosis ha e shorter sur i al than those who ha e quit. Passi e smoking is a cause of lung cancer in non5smokers. 'tudies from the 8.' ha e consistently shown a significant increase in relati e risk among those exposed to passi e smoke.

Unit 1 - Biology and disease Enzymes "n>ymes are complex chemicals that control reactions in li ing cells. "n>ymes are biological catalysts. They can be used o er and o er again. They are effecti e in small amounts. +isco ered in )J?? in yeast, en>yme means .in yeast1. There are ;?,??? different en>ymes in human cells, each controlling a different chemical reaction 2ncrease the rate of reactions by up to )?)# times. 0ithout en>ymes the speed of reactions would not support life.

,n5yme Classification Most en>ymes end with (ase 'ome en>ymes are gi en one word names, where the prefix denotes the substrate eg protease. ,ther en>ymes are gi en systematic names: o =irst word < name of substrate o 'econd word starts with the type of reaction +ehydrogenase ,xidase Phosphorylase $arboxylase +ecarboxylase Polymerase o $omplete third word with suffix (ase "g cytochrome oxidase "g +!A polymerase ,n5yme structure and function o "n>ymes are globular proteins. o Their function is determined by their complex structure. o The reaction takes place in the active siteo ,nly a few amino acids are in ol ed ( catalytic amino acids. o The tertiary structure brings them together. o The substrate binds here, the rest of the protein acts as support. o "n>ymes are specific, they only bind with one substrate and control one reaction. o The substrate and the acti e site are complementaryo "n>ymes combine with their substrates to from temporary en5yme'substrate comple es. o They are released as products due to their change in shape. o "n>ymes are not altered or used up by reactions, so can be re5used. o Many en>ymes need other chemicals to function ( coen5ymes o "n>yme function can be slowed or stopped by inhibitors "n>yme T 'ubstrate "n>yme5substrate complex "n>yme T Products

Unit 1 - Biology and disease Mechanism of action )& 6ock and key hypothesis - This is a rigid model where the shape of the acti e site is the in erse shape of the substrate. The acti e site is complementary to the substrate. - The substrate fits into this precise shape forming the en>yme5substrate complex. - This theory does not fully explain the stabili>ation of the en>yme5substrate complex.

#& 2nduced fit hypothesis - 7enerally accepted theory. - Acti e site is not rigid shape - The substrate is attracted to the acti e site. - This causes the acti e site to change shape and it moulds around the substrate. - The en>yme5substrate complex is formed, and the en>yme carries out its catalytic function. - The products ha e a different shape, so are no longer complementary to the acti e site. - The products therefore detach. - "n>yme re erts to original state until another substrate arri es.

%ctivation ,nergy o 2n chemical reactions, old bonds are broken and new ones form. o The energy needed to break these bonds is the activation energyo The substrate requires energy from heat to react. o "n>ymes lower the acti ation energy, allowing reactions to take place at lower temperatures. o This increases the likelihood of the correct reaction taking place, and increase the rate of reaction.

Unit 1 - Biology and disease

=actors affecting the rate of reaction 9/ (emperature "n>ymes ha e an optimum temperature at which they work fastest 2n humans this is approx -IR$ Cinetic energy 2ncreasing temperature increases kinetic energy. 2ncreases number of collisions. 2ncreasing rate of reaction. +enaturation 2ncreasing temperature ibrates molecules iolently breaks hydrogen bonds and other cohesi e forces -+ shape altered Acti e site no longer fits substrate Approx 9?R$ in humans

Unit 1 - Biology and disease :/ o o o o o o pH "ach en>yme works best at a particular p* %optimum&, normally I. Protease en>ymes in the stomach work at p* )5#. p* affects the charge of the amino acids at the acti e site. This affects the ionic bonds. The substrate can no longer bind. $hange in p* can denature en>ymes.

;/ "ubstrate concentration o The rate of reaction increases as the substrate concentration increases, until the en>yme is working at full capacity. o This is due to more collisions between the en>yme and the substrate. o 2n low substrate concentrations, not all en>yme molecules are being used o As the substrate concentration increases more en>yme molecules are used. o 0hen all acti e sites are in use, substrate concentration does not affect rate.

Unit 1 - Biology and disease ,n5yme inhibition o 2nhibitors can slow down or stop the catalytic acti ity of en>ymes. o 2nhibition is a natural process, a mechanism to switch en>ymes on or off when needed. o 2nhibition tends to be reversible as the en>yme returns to normal when the inhibitor is remo ed. o De ersible inhibitors can be competitive or non'competitive 9-Competitive inhibitors $ompete with substrate molecules to occupy the acti e site. *a e similar structure to substrate but cannot be con erted to products. Deduce number of en>yme5substrate complexes being formed. 'ame final amount of product formed, it :ust takes longer. 2f equal amount of substrate and inhibitor, rate is hal ed. 2ncrease in concentration of substrate reduces effect of inhibitor. "xample: - Malonic acid inhibits the action of succinic dehydrogenase on succinic acid in the Crebs cycle. - This is feedback inhibition and reduces further production of malonic acid until its concentration is decreased at lower le els.

:- Non'competitive inhibitors 3ind to en>yme away from acti e site ( allosteric site. This can be used in metabolic pathways: Allows sophisticated control of the rate. This self5regulation is an example of negati e feedback. $hange the o erall shape of the molecule including the acti e site. There is no competition for the acti e site. Deduce the amount of acti e en>yme molecules. 'o decrease the maximum rate of reaction. 2ncrease on concentration of substrate does not reduce effect of inhibitor.

Unit 1 - Biology and disease "g Amylase is acti ated by chloride ions. 'ome are metabolic poisons: "g cyanide inhibits cytochrome oxidase, inhibiting aerobic respiration.

Unit 1 - Biology and disease !igestion Ingestion: the taking of nutrients into the organism. Nutrients: organic molecules in food. Most of these are large and insoluble. !igestion: the process by which large, insoluble organic molecules in food are broken down into small, soluble organic molecules, to enable their absorption into the blood stream. %bsorption: the process by which small, soluble nutrient molecules pass from the lumen of the gut into the blood stream. %ssimilation: the processes by which the cells metabolise the nutrient molecules. ,gestion: the remo al of undigested food molecules from the organism %in humans this is mainly cellulose&. *umans are heterotrophs 5 they take nutrients in from their surroundings. They digest food, and absorb simple molecules that are produced. To do this they need a gut2n mammals this is an alimentary canal This is a muscular tube from mouth to anus. The alimentary canal is in well defined regions o buccal ca ity %mouth& o oesophagus o stomach o small intestine: duodenum ileum o caecum o appendix o large intestine: colon rectum +igesti e system consists of alimentary canal and glands that secrete into it. o 'ali ary glands ( into mouth o Pancreas ( into duodenum o 6i er % ia the gall bladder& ( into duodeum

Unit 1 - Biology and disease

Carbohydrate digestion (he mouth .buccal cavity/ 8ses lips, tongue and teeth to masticate %chew& food to increase surface area. - pairs of sali ary glands produce sali a: "alivary amylase hydrolyses starch to maltose %4 )5; links&. Mucin %mucus& binds food into bolus lubricated for swallowing. Alkali neutralises any acid in the food. (he oesophagus 3olus pushed by tongue to back of mouth. "piglottis pre ent food entering trachea. Mucus secreted from glands to lubricate food. Peristalsis pushes bolus to stomach. (he stomach Muscular bag, approx holds ).# litres can increase to H litres when distended. Protein digestion starts here. $on erts food into semi solid chyme by peristaltic churning 7astric mucosa embedded with gastric pits that produce gastric :uice. 7astric :uice contains: o 0ater o hydrochloric acid ( creates p* # which kills bacteria ( this denatures amylase. o pepsin ( digests proteins, so digests the amylase. $hyme is gradually released o er -5; hours. Pyloric sphincter controls exit in small squirts. (he small intestine , er 9 metres in lengths !uodenum is approx #Hcm in length. Ileum is o er H.H metres.

Unit 1 - Biology and disease 6uminal epithelium %inner tissue layer& is folded into villi ( ?.Hmm to )mm long o increase surface area o in contact with more food. 6uminal epithelial e is folded into micro illi o =urther increase surface area.

!igestion in the small intestine There are three main secretions of digesti e :uices: Bile $reated by the li er. 'tored in gall bladder. 'ecreted ia bile duct into small intestine. $ontains no en>ymes. $ontains alkali which neutralises acidic chyme for en>ymes.

Pancreatic <uice 'ecreted by the pancreas ia the pancreatic duct to the duodenum. 2t is alkaline to neutralise stomach acid, pro ides optimum p* for en>ymes. $ontains arious en>ymes, including: o Pancreatic amylase ( this completes hydrolysis of starch to maltose. Intestinal <uice 'ecreted from the cells co ering illi. $ontains alkali and mucus. $ontains few, if any, en>ymes. Membrane'Bound ,n5ymes 3ound to luminal membrane of epithelial cells. May be found in intestinal :uice due to sloughing of these cells. o $arbohydrases ( hydrolyse glycosidic bonds, releasing monosaccharides: 'ucrase digests sucrose to glucose and fructose Maltase digests maltose to glucose 6actase digests lactose to glucose and galactose %bsorption in the small intestine Absorption of small soluble molecules from the lumen, across the epithelium, into the blood. 0ater is absorbed by osmosis mainly in the large intestine. 'ome solutes enter the epithelium by diffusion and facilitated diffusion. Most substances rely on acti e transport. *owe er, glucose relies on indirect active transport: o 'odium ions are pumped out of the cytoplasm on the membrane facing away from the lumen %non5lumenal membrane& o This creates concentration gradients for sodium from the lumen into epithelium.

Unit 1 - Biology and disease o 7lucose enters cytoplasm ia sodium5glucose co5transporters:

). The transporter faces into the lumen 5 at this point it is capable of binding sodium, but not glucose. #. 'odium binds, causing a change that allows the glucose to bind. -. 7lucose binds and the transporter changes shape allowing sodium and glucose to be mo ed inside the cell ;. 'odium and glucose detach from the co5transporter into the cytoplasm. This establishes a concentration gradient for glucose from cytoplasm towards the blood. 7lucose lea es the cytoplasm by facilitated diffusion.

%daptations of the small intestine .ileum/ to ma imise absorption: 6arge surface area: o 6ong ( 9m o =olded o /illi o Micro illi Maintaining concentration gradients: o Peristalsis deli ers more nutrients o Acti e transport remo es nutrients from lumen o "xtensi e capillary network pro ides an excellent blood supply to remo e nutrients from epithelial cells. 'hort distances: o ,ne cell thick epithelium o $apillaries lie next to epithelial cells. o Thin walls around capillaries. (he large intestine

Unit 1 - Biology and disease "xcess water from digesti e secretions are absorbed. The undigested food is expelled as faeces.

*actose intolerance 6actose is the ma:or sugar found in milk. 2t is a disaccharide. 6actase hydrolyses lactose into glucose and galactose. These are then absorbed into the blood stream. 6actose production naturally declines slightly after childhood. People with lactose intolerance do not secrete enough lactose. They are unable to digest significant amounts of lactose. 6actose remains in the intestines. 3acteria metabolise this sugar, and produce large olumes of gas. This causes abdominal bloating, cramps and flatulence. The lactose reduces the water potential in the intestines. The large intestine cannot reabsorb enough water. This can result in diarrhoea. Causes ). Primary lactase deficiency: 7enetic factors cause the production of lactase to decline at a young age %after # years old&. #. 'econdary lactase deficiency +iseases can reduce the lactase production. "xamples ( $eliac disease and $rohn1s disease. Cholera An infectious disease caused by the bacterium Vibrio cholerae. Transmitted through ingesting contaminated water or food. 2f enough are consumed, some may sur i e stomach acid. They use their flagella to propel themsel es into the epithelial cells. $holera produces toxins. These interact with chloride protein pumps in the small intestine. This increases secretion of chloride ions into the lumen of the small intestine. This establishes a water potential gradient from the epithelium into the lumen. /ast quantities of water are lost by osmosis. This results in se ere diarrhoea. This results in se ere dehydration. Also, essential electrolytes are lost ( these are ions, including sodium and potassium. These are required for metabolic processes in cells. /omiting may also exacerbate fluid losses. 2nternal organs fail, coma results, followed by cardiac arrest and death. Oral rehydration solution .O#"/ & Oral rehydration therapy-

Unit 1 - Biology and disease A mixture of glucose and electrolytes %sodium, potassium, chloride and citrate ions& in sachets. "ach is mixed with a specific olume of water %) litre&. This pro ides a specific concentration of glucose and electrolytes. 0ater ( for rehydration 'odium ( enables use of sodium5glucose cotransporters. 7lucose ( also enables use of sodium5glucose cotransporters. Therefore, sodium and glucose can be absorbed quickly. Potassium, chloride and citrate ions can also be absorbed. Minimal training and expertise is required to administer this. 2t is relati ely cheap, and can sa e many li es in de eloping countries.

(esting and trialling ne0 drugs ). Desearch leads to the de elopment of a new drug. #. Apply for a patent. -. 2n estigate potential ad erse effects by chemical testing and using laboratory animals. ;. Test on small group of healthy olunteers %eg H?& to check for side effects. H. Test on a larger group who ha e the disease %eg #??& to check for effecti ity. 9. +ouble blind trial on a much larger group with the disease. *alf recei e a placebo ( treated exactly the same but recei e no acti e ingredient. *alf recei e the acti e ingredient. !either patient nor doctor know who recei es which. Desults are sent to research scientists. I. =indings are published in a :ournal. ,ther scientists re iew the findings %peer re iew&. They may replicate the experiments to check for repeatability of the results. A. A licence may be granted many years after the initial de elopment, by which time there may not be many years left for the patent. J. Monitoring continues all the time the drug is a ailable. ,thical issues associated 0ith O#" use Patients are already se erely ill. They may not be in a fit state to commit to the trial. Also, new formulations may not work. They may e en make the symptoms worse. 2n double blind trials, half the patients recei e no acti e ingredients, so will not impro e. 7reatest incidence of diarrhoea diseases is in de eloping countries. Pharmaceutical companies profit from this. Also go ernments may recei e payments, but the patients may not be recompensed. *uman rights issues ha e impro ed in recent years.

Unit 1 - Biology and disease *ungs = Gas e change "tructure of the thora *ungs 'ite of gaseous exchange 6ocated in thorax Dequire entilation 6eft smaller than right ( it o erlaps the heart #ib cage 3ony case enclosing lungs and heart )# pairs attached dorsally to ertebrae Top )? pairs are attached entrally to sternum, remaining ribs are .floating1 Muscles 2ntercostal muscles between ribs, responsible for mo ement "xternal ( contracts ( ribs mo e up and out 5 inspiration 2nternal ( contract ( ribs mo e down and in 5 expiration +iaphragm ( muscular sheet which separates thorax from abdomen Pleural membranes # membranes that secrete pleural fluid. The fluid filled ca ity is lower than atmospheric pressure. This pre ents the lungs deflating.

Unit 1 - Biology and disease %ir 0ays (rachea Dings of cartilage pre ent tube collapsing when internal pressure drops. 6ined with ciliated epithelium. Bronchi Trachea di ides into # bronchi. These tubes enter each lung 'upported by cartilage Bronchioles 3ranch throughout each lung. 'upport from cartilage gradually decreases %lveoli 'pherical sacs Ma:or site of gas exchange )??Mm in diameter 6ined with flattened epithelial cells %approx -?? million& Makes a ast area for exchange %;?59?m #&

Unit 1 - Biology and disease

Histology of the breathing system ,pithelial tissue: 'imple cells arranged in single or multilayered sheets, co ering the internal and external surface of the body of an organism. They often form exchange surfaces in the body, with capillaries pro iding the blood supply. # types of epithelium in the al eoli: o (ype I: =lattened, squamous %like cra>y5pa ing&. 'urround al eolar wall /ery thin diffusion pathway o (ype II: 'ecrete surfactant A mixture of lipids and proteins. Deduces surface tension. Pre ents al eoli collapsing and pro ides elastic recoil for lungs Connective tissue 'upporting layer beneath epithelium. Made of fine fibres ( collagen and elastin Blood vessels $apillary walls are made of endothelial cells. =lattened cells forming a narrow tube with a common basement membrane. Pores %fenestrations& between cells enable exchange. "xtremely narrow, so red blood cells squee>e through. 'lows down passage allowing more time for diffusion. 2ncrease surface area of cell in contact with endothelium !etwork of capillaries from pulmonary artery. 8nite to form pulmonary ein.

Unit 1 - Biology and disease Gas , change 7ases are exchanged due to concentration gradients. ,xygen diffused into blood from al eolar air. $arbon dioxide diffuses into al eolar air from blood. 7as ,xygen $arbon dioxide !itrogen 0ater /apour $ic14s la0: Date of diffusion is proportional to: surface area U difference in concentration Thickness of surface 'urface area: o 6arge due to al eoli. o Many small spherical sacs. $oncentration gradients maintained through: o Pulmonary entilation o $irculation of the blood. Thickness of surface: o 'ingle layer of squamous epithelium o '2ngle layer of endothelium Percentage /olume 2nspired air "xpired air #?.J? )H.?.?-.9 IA.9? I;.J ?.;I 9.#

Unit 1 - Biology and disease Pulmonary ventilation & Breathing Air mo ements occur due to pressure difference between atmosphere and al eolar air 2f intrapulmonary pressure V atmospheric pressure < "xpiration 2f atmospheric pressure V intrapulmonary pressure < 2nspiration Pressure differences are achie ed in the thoracic ca ity Through the action of the intercostals muscles and positioning of the diaphragm. A pleural sac surrounds each lung. The outer membrane is attached to the rib cage, the inner to the lungs. The inner ca ity is at a pressure below atmospheric pressure. This pre ents the lungs deflating. 0hen the thorax mo es, the lungs do too. Al eoli are elastic and collapse if not held stretched by the thorax. The secrete surfactant which pre ents them sticking together.

Mechanism of inspiration $ontraction of diaphragm $ontraction of external intercostal muscles Pulls ribs upwards and ,utwards +iameter of thorax increases

=lattens and descends

Thorax ca ity lengthens

2ncrease in thorax olume 6ungs expand Al eolar pressure drops Pressure gradient established =rom atmosphere to al eoli 2!'P2DAT2,!

Unit 1 - Biology and disease Mechanism of e piration Delaxation of diaphragm $ontraction of internal 2ntercostal muscles Dibs mo e downwards And inwards +iameter of thorax +ecreases

Deturns to domed position

Thorax ca ity shortens

+ecrease in thorax olume "lastic recoil of lungs 6ungs decrease in si>e 2ncrease in intrapulmonary pressure Pressure gradient established from Al eoli to atmosphere "UP2DAT2,! $orced inspiration>e piration Abdominal muscles used This greatly increases intrapulmonary pressure "g. coughing or blowing up balloon.

Unit 1 - Biology and disease Measurements of pulmonary ventilation "pirometer Measures olumes of air expired and inspired 8sed to diagnose entilation deficiencies $reates a spirogram Tidal olume %T/&: /olume of air breathed in or out during quiet breathing About H??cm- in adults 3reathing rate < the number of inspirationGexpiration cycles per minute Pulmonary entilation < tidal olume U breathing rate ie the olume of air breathed in or out per minute during quiet breathing. (he biological basis of lung disease Pulmonary tuberculosis Tuberculosis %T3& is an infectious disease 2t is caused by the bacterium Mycobacterium tuberculosis. T3 most commonly affects the lungs but also can in ol e almost any organ of the body. Today T3 usually can be treated successfully with antibiotics.

(ransmission 'omeone who has a T3 lung infection coughs, snee>es, shouts, or spits. People who are nearby can then possibly breathe the bacteria into their lungs. A person can become infected with T3 when minute particles of infected sputum are inhaled from the air. Lou donSt get T3 by :ust touching the clothes or shaking the hands of someone who is infected. Tuberculosis is transmitted primarily from person to person by breathing infected air during close contact. There is a form of atypical tuberculosis, howe er, that is transmitted by drinking unpasteuri>ed milk. Course of infection 0hen the inhaled tuberculosis bacteria enter the lungs, they multiply. This causes a local lung infection %pneumonia&. The local lymph nodes associated with the lungs may also become in ol ed with the infection and usually become enlarged. 2n addition, T3 can spread to other parts of the body. The bodySs immune %defense& system, howe er, can fight off the infection and stop the bacteria from spreading.

Unit 1 - Biology and disease The immune system does so ultimately by forming scar tissue around the T3 bacteria and isolating it from the rest of the body. 2f the body is able to form scar tissue around the T3 bacteria, then the infection is contained in an inacti e state. 'uch an indi idual typically has no symptoms and cannot spread T3 to other people. The scar tissue and lymph nodes may e entually harden, like stone, due to the process of calcification of the scars %deposition of calcium from the bloodstream in the scar tissue&. These scars often appear on x5rays and imaging studies like round marbles and are referred to as a granuloma. 'ometimes, howe er, the bodySs immune system becomes weakened, and the T3 bacteria break through the scar tissue and can cause acti e disease, referred to as secondary T3. T3 can spread to other locations in the body: o The kidneys, bone, and lining of the brain and spinal cord %meninges&.

"ymptoms T3 infection usually occurs initially in the upper part of the lungs. The usual symptoms that occur with an acti e T3 infection areO o 7eneral tiredness or weakness o 0eight loss, o =e er, and night sweats. 2f the infection in the lung worsens, then further symptoms can include: o $oughing o $hest pain o $oughing up of sputum %material from the lungs& andGor blood o 'hortness of breath. 2f the infection spreads beyond the lungs, the symptoms will depend upon the organs in ol ed. Pulmonary $ibrosis Pulmonary =ibrosis in ol es scarring of the lung. 7radually, the air sacs of the lungs become replaced by fibrotic tissue. 0hen the scar forms, the tissue becomes thicker. +iffusion distances are increased. This causes an irre ersible loss of the tissues for efficient gaseous exchange. "ymptoms 'hortness of breath, particularly with exertion $hronic dry, hacking cough =atigue and weakness +iscomfort in the chest 6oss of appetite Dapid weight loss Causes 2t could be an autoimmune disorder, and there may genetic predisposition.

Unit 1 - Biology and disease The fibrotic process is a reaction to microscopic in:ury to the lung. Macrophages accumulate in connecti e tissue. They stimulate the creation of fibrous tissue. Associations ha e been made with the following: 2nhaled en ironmental and occupational pollutants $igarette smoking +iseases such as 'cleroderma, Dheumatoid Arthritis, 6upus and 'arcoidosis The after effects of a iral infection $ertain medications Therapeutic radiation

%sthma Asthma causes the bronchi to become inflamed and swollen. 3ronchi are more sensiti e than normal. 2t could be inherited. 2t could also be caused due to a lack of exposure to certain substances in early childhood. (riggers: $ertain substances, or triggers, can irritate them: o *ouse dust mites o Animal fur o Pollen o Tobacco smoke o $old air o $hest infections. "ymptoms: 0hen the bronchi are irritated, they become narrow and the muscles around them tighten. This can increase the production of sticky mucus. This causes whee>ing and coughing and shortness of breath. Pulmonary entilation is reduced. This effects the maintenance of efficient concentration gradients in the al eoli. This results in inefficient gas exchange. The se erity of the symptoms of asthma differs from person to person, from mild to se ere. The narrowing of the airways is usually re ersible 5 occurring naturally, or through the use of medicines. A se ere asthma attack can be life threatening and may require hospital treatment. ,mphysema "mphysema causes the walls of the al eoli to break down. 6arger air spaces are formed. Total surface area a ailable for gas exchange is greatly reduced. Causes: The single most common cause of emphysema is smoking.

Unit 1 - Biology and disease *ea y cigarette smokers are most at risk from emphysema and chronic bronchitis. The damage to your airway begins when tobacco smoke temporarily paralyses the cilia that line the bronchial tubes. These hairs usually sweep irritants and pathogens out of the airways, The temporary paralysis pre ents them from doing this. The irritants remain in your bronchial tubes and pass into your al eoli This inflames the tissue and damaging the walls. 3reathing in industrial pollutants can also contribute to the de elopment of emphysema. 2n a few, rare cases %about #@& emphysema is the result of defecti e genes. This type is called alpha antitrypsin %AAT& deficiency emphysema. AAT is a protein that blocks the action of an en>yme that breaks down the walls of the al eoli. 2f you are deficient in the protein, it can lead to progressi e damage that will e entually result in emphysema.

"ymptoms 'hortness of breath when exerting yourself. " entually, this shortness of breath may occur e en when you are at rest. +ifficulty breathing $oughing 0hee>ing "xcess mucus production A bluish tint to the skin %cyanosis&

Unit 1 - Biology and disease (he Heart Position Middle of thorax Abo e diaphragm 3ehind sternum 3etween # lungs Partially o erlapped by left lung Apex points towards left of thorax. Cardiac muscle Ma:or tissue in the heart wall is cardiac muscle $ardiac muscle tissue < myocardium 3ranching cells which can share nuclei $ells are cross striated like skeletal muscle. Transmit electrical excitation $apable of contracting and relaxing repeatedly for life. Blood supply Pro ided by coronary artery +eli ers oxygenated blood to the heart muscle 3ranches from aorta Decei es H@ of total cardiac output +ense capillary network $oronary eins return blood to heart directly into right atrium through coronary sinus.

Unit 1 - Biology and disease

%ssociated Blood 2essels 2ena Cava o $arries deoxygenated blood from body tissues into right atrium. Pulmonary artery o $arries deoxygenated blood from right entricle to lungs Pulmonary vein o $arries oxygenated blood from lungs back to left atrium. %orta o $arries oxygenated blood from left entricle to respiring body tissues.

Internal structure Atria %sing. Atrium&: o Delax to recei e blood from eins: /enae ca ae into right atrium Pulmonary eins into left atrium. o Thin walled o "lastic o $ontract to push blood into entricles: Dings of muscles surround eins at their point of entry $ontract to close off eins. Pre ents reflux of blood into eins. /entricles: o Myocardium thicker than atria. +istance to entricles is ery small. o Myocardium of left entricle - times thicker than right. $reates higher blood pressure in systemic circulation: o "ssential for efficient function of organs. o Allow for tissue fluid formation. 6ower blood pressure in pulmonary circulation: o Pre ents rupture of delicate pulmonary arteries. o 'eparated by septum. o Delax to recei e blood from atria. o $ontract to push blood through arteries: 6eft entricle into aorta. Dight entricle into pulmonary artery. 2alves Desponsible for heart sounds. "nsure unidirectional flow of blood though heart. %trioventricular valves : o 3etween atria and entricles. o Pre ent blood flowing back into atria when entricles contract.

Unit 1 - Biology and disease o *igher pressure in entricles causes them to close back towards atria. o $auses .lub sound1. o $hordae tendinae: =ibrous cords Attach loose edge of al es to wall of entricle. o Attached by papillary muscle: $ontract when entricle contracts. Tighten the chordae tendinae. o Tricuspid al e: - flaps. Dight side of heart. o 3icuspid al e %mitral al e&: # flaps. 6eft side of heart. Poc1et>semilunar valves : o At entrance of aorta and pulmonary artery. o *ence aortic and pulmonary al es. o Pre ent back flow of blood into entricles. o 0hen entricles relax o Pressure in entricle drops below pressure in arteries. o $auses al es to fill with blood. o $reates .dub1 sound

(he Cardiac Cycle A rhythmic series of e ents. Desulting in each beat of the heart. At rest, a erage I# beats per minute. ,ne cardiac cycle < approx ?.A- secs. !iastole: o Delaxation of atria and entricles. o Atria fill with blood from eins. o Pocket al es close ( dub. o 3lood starts to mo e into entricles. %trial systole: o Atria contract. o 2ncreases pressure. o Pushes blood into entricles. o Passes though atrio entricular al es. o /entricles remain relaxed. 2entricular systole: o /entricles contract. o Atria relax. o *igher pressure in entricles than atria. o Atri entricular al es close ( lub.

Unit 1 - Biology and disease o Pocket al es open. o 3lood flows into arteries. Pressure Changes !uring the Cardiac Cycle 3lood always flows from a high pressure to a lower pressure, unless pre ented by al es. 7raph starts at atrial systole o Point at which atrial pressure rises abo e ? kPa /entricular systole occurs when pressure in entricles exceeds pressure in atria. o A./. al es close. o $auses increase in pressure in atria. 3lood flows into arteries when pressure in entricles exceeds pressure in arteries. o Pocket al es open. +iastole occurs when pressure in entricles drops below pressure in arteries. o Pocket al es close. o Pressure in arteries maintained relati ely high. o +ue to elastic recoil of artery walls. Atrio entricular al es open when pressure in entricles drops below pressure in atria. o Pressure in atria rises back towards ? kPa as they fill with blood.

Unit 1 - Biology and disease

, tra detail: ,lectrocardiogram .,CG/ "lectrodes placed on skin. $hanges in oltage displayed on oscilloscope: o P wa e < electrical excitation of atria o WD' complex < excitation of entricles. o T wa e < reco ery %repolarisation& of entricles. Phonocardiogram .PCG/: Decords heart sounds. $aused by al es closing. 6ub dub. Conducting tissues of the Heart The heart beat is initiated from within the heart muscle. *eart muscle is myogenic: o 2t is self exciting. o 2t can contract on its own without needing ner e impulses.

Unit 1 - Biology and disease 2t maintains a continuous, inherent rhythm through electrical excitation of localised areas. This leads to contraction of cardiac muscle. This is called myogenic stimulation. Modified cardiac muscle cells coordinate this sequence of e ents. They conduct the excitation through the walls of the heart.

"ino %trial Node ."%N/: 'mall group of specialised cells. 2n wall of right atrium. !ear opening of superior ena ca a. Deferred to as the .pacemaker1. 2nitiates the heart beat. "lectrical excitation passes across both atria causing them to contract. %trio 2entricular Node .%2N/: 'mall group of specialised cells. 3etween the # atria. "lectrical acti ity reaches the A/! +elays passage of excitation down the septum This enables the atria to empty before entricles contract Passes electrical excitation down septum. Bundle of His: 'pecialised non5contractile cardiac muscle fibres %Purkin:e fibres& 6ead down the inter entricular septum to apex. "lectrical excitation passes down this. They radiate upwards from the apex around the entricle walls. "xcitation passes up through these. /entricle contracts from apex upwards.

Unit 1 - Biology and disease Cardiac output !ormal heart rate < approx I# beats per minute. /aries from H? to #?? beats per minute. Approximately IH cm- of blood pumped from each entricle. $ardiac output is the olume of blood pumped by one entricle of the heart in one minute $ardiac output < heart rate U stroke olume. Measured in dm-min5) Heart !isease %theroma An accumulation and swelling in artery walls that is made up of cells that contain lipids and fibrous connecti e tissue. Also referred to as plaques. The swelling occurs between the endothelium lining and the smooth muscle wall of the artery They occur due to macrophages that ha e taken up low5density lipoprotein %6+6&. This is associated with high cholesterol le els. This is associated with high le els of saturated fats in the diet. The plaque calcifies and hardens o er time. %neurysm Atheroma can cause weakening of the arterial wall. $an be due to atheroma. This can lead to a locali>ed, blood5filled dilation %balloon5like bulge& of a blood essel. Aneurysms most commonly occur in: o Arteries at the base of the brain ( causing a stroke o Aorta. The bulge in a blood essel can burst. This results in haemorrhage. The larger an aneurysm becomes, the more likely it is to burst. (hrombosis Thrombosis occurs if a plaque breaks through the endothelium. 2t de elop a rough surface. This causes the formation of a clot or thrombus inside a blood essel. This obstructs the flow of blood through the circulatory system. 2t can be dislodged, being carried down into smaller arteries, blocking blood flow. The tissue affected is star ed of essential nutrients and oxygen. 0hen thrombosis affects important arteries it can be fatal or cause serious illness: o 2n the coronary arteries it may cause a heart attack ( myocardial infarction o 2n the brain with blood it may cause a stroke. Coronary Heart !isease

Unit 1 - Biology and disease $oronary heart disease %$*+& occurs due to the accumulation of plaques within the walls of the coronary arteries. These supply the myocardium %the muscle of the heart& with oxygen and nutrients. Most indi iduals with $*+ show no e idence of disease for decades as the disease progresses. 7radually, blood flow to the heart muscle reduces. This puts extra strain on the heart.

Myocardial infarction Myocardial infarction is commonly known as a heart attack. ,ccurs when a dislodged thrombosis enters a coronary artery, or one of its branches. The blood supply to a part of the heart is interrupted. The resulting ischemia or oxygen shortage, if left untreated for a sufficient period, can cause damage andGor death of heart tissue. 2t is the leading cause of death for both men and women all o er the world. Infarction < tissue death due to oxygen star ation. 2t can be the cause of cardiac arrest, which is the stopping of the heartbeat. 'e ere myocardial infarction may lead to heart failure, in which the pumping action of the heart is impaired. 'ymptoms of acute myocardial infarction includeO o chest pain %typically radiating to the left arm or left side of the neck& o shortness of breath o nausea, omiting o palpitations, sweating, and anxiety %often described as a sense of impending doom&. #is1 factors *ereditary factors ( can increase the risk of high cholesterol and high blood pressure. *igh cholesterol: o "ssential for cell membranes. o *owe er, high le els can cause plaques. o +ue to a high concentration of low5density lipoproteins in the blood. o This is linked to high le els of saturated fats in the diet. *igh blood pressure. o Puts more stress on blood essels. o 2ncreases risk of aneurysms or thromboses. o $an also cause blood essels to harden and thicken, reducing blood flow o /arious risk factors: 'alt ( can increase blood pressure 'moking: !icotine causes a narrowing of arteries, leading to high blood pressure. $arbon monoxide reduces how much oxygen is carried of haemoglobin. The heart works harder to supply the tissues with oxygen. This also increases blood pressure. 'tress o To reduce the risk of heart disease:

Unit 1 - Biology and disease 2ncrease intake of antioxidants eg itamin $ 2ncrease fibre intake 5 cellulose Age ( 2ncidence increases in men o er 9? and women o er 9H.

Unit 1 - Biology and disease Immunology Phagocytosis Process by which large particles are taken up by cells. /ia plasma membrane deri ed esicles. A form of endocytosis. # reasons for phagocytosis: o To protect against pathogens. Pre ents them spreading To dispose of dead, dying or damaged cells. Process: o *istamine released where tissue is damaged: o This attracts phagocytes o 2t causes dilation of blood capillaries. o Tissue fluid escapes into tissues. o $auses inflammation. o Phagocytes pass into tissue fluid. o Pathogens release chemicals. o Phagocyte mo es towards the pathogen up the concentration gradient. o The pathogen attaches to the phagocyte o The phagocyte forms pseudopodia around the pathogen. o The edges of the pseudopodia meet and fuse. o This encloses the pathogen in a phagosome. o 6ysosomes migrate towards the phagosome. o They fuse with the phagosome and release lytic en>ymes inside it. o These en>ymes break down the pathogen. o The products are absorbed by the pahgocyte. o 2f the phagocyte sur i es it may carry out more phagocytosis. o Pus < dead bacteria and phagocytes. (he Immune #esponse Antigens < specific chemicals on the cell surface membrane of foreign cells %non5self&. They are characterisitic of the indi idual. They may be: o Proteins o Polysaccharides o 7lycoproteins o 7lycolipids "g red blood cells ha e isohaemaglutinnogen A or 3, or both or neither. =oreign cells ha e foreign markers ( antigens. Decognised as foreign by leucocytes. o ,n cell surface of a microorganism. o ,n the surface of a irus. o ,n the cell surface of a tissue or organ transplant. Pro oke an immune response.

Unit 1 - Biology and disease (he role of %ntigen presenting cells .%PCs/: Macrophages ingest bacteriaG iruses. +isplay bacterial antigens on membranes. .Antigen presentation1. Attach to specific T and 3 cells in lymph nodes. *ymphocytes # main groups: o T cells: Mature in the thymus $ause a cellular response to infection. o 3 cells: Mature in the bone marrow. $ause a humoral response to infection. They release antibodies. 'pecificity: o "ach T and 3 cell is able to react with one antigen. o There are receptor sites on the surface membrane. o These pro ide the specificity in antigen binding. o Antigens of the bodySs own cells are excluded. o $apable of differentiating between SselfS and Snon5selfS. o ,nly react against the Snon5selfS molecules. ( foreign antigens. Production of lymphocytes ,riginally deri e from stem cells of the bone marrow. Pass to the lymph glands in the chest, where: o They multiply. o They are processed and acti ated. o ,ccurs largely during foetal life and early childhood. o They are tested for their ability to recognise and bond to antigens. o 3y AP$s. o 2f they bond the T and 3 cells are killed. o Those that sur i e will recogni>e foreign antigens. There is theoretically a pair of T and 3 cells for each potential foreign antigen. "pecificity: "ach T5cells is able to react with one antigen. Deceptor sites sit on the surface membrane. Pro ide the specificity in antigen binding. Antigens of the bodySs own cells are excluded. $apable of recognising SselfS and Snon5selfS. ,nly react against the Snon5selfS molecules.

Unit 1 - Biology and disease Cellular Immune #esponse by ( cells T cells are approached by AP$s ( clonal selection 'pecific T cell responds. T cells will only respond to antigens presented in this way. =orm clones by mitosis ( clonal expansion /arious types of T cells are produced. Helper ('cells o %These are the type of cell attacked by *2/.& o 'ecretes small proteins called cytokines. o Acti ate Ciller T cells to multiply. o 'timulate AP$ to destroy itself. o Acti ate 3 cells to respond to antigens. ?iller ('cells o +estroy infected cells. o Delease protein that instructs the cell to destroy itself. o ,pen protein pores in membrane. o Affect permeability of cell. o $ell bursts. o This pre ents iruses replicating inside the cell. o Deduces chances of other cells being infected. Memory ('cells o Demain in the body after the pathogens ha e been killed. o "nable rapid response to future infection. Humoral immunity by B cells %ntibodies: o Proteins called immunoglobulins. o Produced by 3 cells, o Most L5shaped. o # identical binding sites for its antigen. o ,ne on either arm. o ; polypeptide chains. o # identical hea y chains. o # identical and smaller light chains o *eld together by disulphide bonds.

Unit 1 - Biology and disease

Process: o 3 cells ha e some of their specific antibodies attached to their cell membrane. o These act as specific receptors. o AP$s attach to these on a specific 3 cell ( clonal selection. o T cells release cytokines which cause the 3 cell to proliferates by mitosis ( clonal expansion. o =orms millions of clones. o Delease them into the circulation at the lymph nodes. o 'ome of the acti ated 35cells turn into memory cells. o ,ther clones are called plasma cells. o These produce specific antibodies. o #??? per second. o Attach to specific antigens. o =orm antibody5antigen complexes. (he role of antibodies: o Agglutination of antigens. o Precipitation of soluble toxins. o 'timulation of phagocytosis. o Pre ent pathogenic bacteria attaching to cell membranes. Immunological Memory o 2nitial immunological response to infection < primary response. o After reco ering from an infection: o The concentration of antibodies against the infectious agent gradually declines. o May take weeks, months, or e en years. o " entually, no antibodies can be detected. o *owe er, the person is still immune. o A second exposure usually brings about a more rapid and larger response to the antigen. o This is called the secondary response. The main features of the secondary antibody response:

Unit 1 - Biology and disease

o The response is specific o +ue to memory cells: o T cells and 3 cells. o $reated during the formation of clones. o 'ome of the progeny cells re ert to small lymphocytes. o Multiply rapidly next time the antigen enters the body. o The secondary reponse is therefore much larger and much faster than the primary reponse. o The person is immune. o Memory cells must ha e long life spans. o Pro ide long5lasting immunity. o 2n fact, there is e idence in humans that some small lymphocytes sur i e at least #? years. %ntigenic variability: ,g Influen5a virus Characteristics of Influen5a o 2nfluen>a is a irus. o 'ingle5stranded D!A genome. o A separate D!A strands. o The genome is enclosed within a lipoprotein en elope. o Also contains en>yme D!A polymerase.

Unit 1 - Biology and disease

Infection: The reser oir is acute infection in other human beings. 'pread is rapid ia aerial droplets through snee>ing. 2nhalation into the respiratory tract. *ost cells are epithelial cells of bronchi and bronchioles 2ts antigens attache to the receptors on outside of the host cell. Taken into the cell by endocytosis. /iral D!A is released into the cell cytoplasm. Cause of disease: The irus takes o er the cellSs producti ity. Toxins are released. This destroys the epithelial cells. 6hy is influen5a difficult to treat8 o Antibiotics do not cure iruses. o $an be used on secondary infections. o 2ts antigens change frequently due to mutations. o Also, the A separate D!A strands. o 2ncrease the potential for recombinants to form. o 7ene segments may interchange if two different iruses infect the same cell. o This may contribute to the rapid de elopment of new flu strains. o A ian and pig strains allow more reser oirs for recombination. o There is great antigenic ariability. o This increases the chance of a irus displaying new antigens to infect the host. o Memory cells do not exist, so a primary immune response is required.

Unit 1 - Biology and disease 2%CCIN%(ION Passive immunity 2ntroduction of antibodies from outside the body !atural ( breast milk Artificial 5 when disease is likely to result in death before immunity is de eloped "g rabies % irus& and tetanus %bacterium& Antibodies are produced by other mammals B serum is in:ected %ctive immunity Production of antibodies by indi idual1s immune system !atural ( response to infection Artificial ( introduction of accines into the body 2accines /accines contain antigens. +eri ed from pathogens. Protect against infection by that organism. 0ithout suffering illness. 2mportant that accine does not trigger symptoms of the disease. ?illed virulent organisms "g cholera bacterium Cilled using chemicals. *ive non'virulent strains "g rubella irus. o 7erman measles. o Mild rash and fe er. Production: o /irulence is greatly reduced by : 7rowing at high or low temperatures or without oxygen or with certain chemicals ,r, encourage mutations by repeated sub culturing. Produces same antigens. 6acks irulence. Isolated antigens from a pathogen "g influen>a irus Production: o 6aboratory procedure. o Demo al of antigens from pathogen. o !o occasional rogue micro organisms. Administration: o 2n:ection into:

Unit 1 - Biology and disease "lderly Medical staff. People with respiratory disorders. o Annual administration. o To pro ide immunity to current strains. !evelopment of ne0 vaccines o !ew accines are created through laboratory research. o Wuite often this is by profit making organisations. o Papers are published. o Methodology needs to be critically assessed by other scientists. o +ifferent scientists ha e different opinions. o ,pinions may be biased due to: o 0hom the scientists work for. o 'cientists current iews and beliefs. o Accepting new scientific de elopments takes time. o ,nce accepted, rigorous testing is necessary before a licence is granted for its production and use. % ne0 vaccine must: o 3e safe and effecti e. o *a e few side effects: o Most accines will ha e some side effects. o These can be acute in some cases. o This could discourage use if people do not consider the accination to be essential. o 3e economically iable ( it must be possible to accinate all ulnerable indi iduals. o *a e a ailable methods of production, transport and storage need to be de eloped, eg is refrigeration necessaryP o 3e accepted by the scientific community if it is to be administered. o 3e accepted by the public. 2accination programmes o /accinations should be administered to the larges possible group of people at the same time. o This is called .herd1 immuni>ation. o Dequires JAH to J?@ of the population to be immunised. o This reduces the chance of the microorganism to find a suitable host. o People who ha e not successfully acquired immunity are therefore less likely to be exposed to the pathogen. o 'ome of these people are likely to be more ulnerable than others, eg young, old and those with compromised immune systems. MM# o A triple accine for: o Measles $an cause con ulsions, disability or death.

Unit 1 - Biology and disease o Mumps $an cause deafness, meningitis, sterility in males. o Dubella 2f infection occurs during pregnancy, it can affect the fetus: +eafness, blindness and other de elopment problems. 2n:ection into infants: o # administrations: o At )# to )H months: $oincides with weaning from breastfeeding. Passi e immunity from Mother declines o At - to H years: 'ome indi iduals do not acquire immunity from the earlier accination 2JAA ( accine introduced #??? 5 +r 0akefiled published a report suggesting that MMD might caused autism. 3ased on tests on #H children. The lawyers working for parents of children with autism funded his research. Many parents opted not to ha e their children accinated. $orrelation noticed ( autism emerged at around ); months. =urther research on much larger samples %-?,??? in Xapan& has shown there was no link. Parents had to assess the conflicting e idence, data and opinions. 2n the mean time, children were not being immuni>ed. 'ome children ha e therefore been badly affected by these diseases. They are not necessarily the children who were not immuni>ed.

o o o o o o o o o o o

,thics of vaccines o +e elopment in ol es animal testing. o Trials are carried out on humans ( who should be testedP o /accination programmes are expensi e: o *ow long should they run forP o 2f accination stops, could the disease re emergeP o "g T3 o 'ide effects are greater in some people than others: o 2n some cases, long5term problems arise. o The incidence of this must be far lower than the chance of getting the disease. o /accinations are not compulsory: o *ow should be encouraged to become immuni>ed. o $ould accination be enforced to pre ent epidemics, eg bird fluP

Unit 1 - Biology and disease Monoclonal antibodies The specificity of antibodies enables them to target other types of molecules found in the body, such as: o receptors or other proteins present on the surface of normal cells. o molecules present uniquely on the surface of cancer cells. The response of the immune system to any pathogen is polyclonal. o Plasma cells manufacture antibodies of a great range of structures in response to the many antigens present on a single pathogen. Monoclonal antibodies are antibodies of a single specificity that are all being synthesised by clones of a single plasma cell that can be grown indefinitely. Production of monoclonal antibodies 2t is difficult to grow plasma cells out of the body. They die out after a few generations because of the limited growth potential of all normal somatic cells. C@sar Milstein and Georges ?Ahler )JIH: Awarded a !obel Pri>e )JA; Plasma can become cancerous. The unchecked proliferation of such a cell is called a myeloma. CYhler and Milstein found a way to combine myeloma cells with plasma cells. They fused myeloma cells with plasma cells from an immuni>ed mouse. The technique is called somatic cell hybridi>ation. The result is a hybridoma.

Unit 1 - Biology and disease

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2mmunise a mouse with the desired antigen. Demo e plasma cells from its spleen. Treat mice to encourage them to de elop cancer tumours. Demo e tumour cells from the spleen. Mix plasma cells with myeloma cells. 8se detergent to facilitate fusion of ad:acent plasma membranes. This creates some hybridomas. I. 'eparate and then culture indi idual cells. A. 2dentify the cells that ha e been produced by successful fusions that ha e the desired qualities: The ability to grow continually The ability to produce large amounts of pure antibody. Problems 0ith monoclonal therapy Mouse antibodies are recognised by the human immune system as foreign. The human patient mounts an immune response against them, producing *AMA %Khuman anti5mouse antibodiesK&. These not only cause the therapeutic antibodies to be quickly eliminated from the host, but also form immune complexes that cause damage to the kidneys. Monoclonal antibodies raised in humans would lessen the problem, but few people would want to be immuni>ed in an attempt to make them and most of the attempts that ha e been made ha e been unsuccessful. 8sing genetic engineering it is possible to make mouse5human hybrid antibodies in an attempt to reduce the problem of *AMA ( $himeric or humani>ed antibodies.

Unit 1 - Biology and disease +ses of monoclonal antibodies $ancer treatment: o The monoclonal antibody is created that is specific to antigens on cancer cells. o 2t is attached to an en>yme that will acti ate a drug that will then only kill the cancer cells. +iagnostic tests to detect small amounts of drugs, toxins or hormones, e.g. monoclonal antibodies to human chorionic gonadotropin %*$7& are used in pregnancy test kits +iagnosis of A2+' by the "62'A test. Monoclonal antibodies can be used to treat iral diseases. There is some e idence to suggest that antibodies may lead to a cure for A2+'. To classify strains of a single pathogen, e.g. Neisseria gonorrhoe. ,thical issues They are potentially a ma:or medical ad ance. $ancer and diabetes ha e been successfully treated. *owe er, there ha e been some deaths associated with their use. Testing requires human olunteers. Production in ol es mice. $ancer is induced in mice. Transgenic mice are being de eloped to humanise the antibodies ( human genes are put into mice.