For a microorganism to be considered a pathogen it must:
- Gain entry to the host
- Colonise the host tissues
- Resist the defenses of the host
- Cause damage to host tissues
Pathogens include bacteria, viruses and fungi. It is a disease causing microorganism.
Microorganisms can gain entry to the body through cut and abrasions in the skin, bites of insects and other animals. Other common points of entry include the gas exchange system and the digestive system. The body linings at these points are moist, thin, have a large surface area and are well supplied with blood vessels.
Microorganisms cause disease by:
- Damaging host tissues. Numbers of pathogens may prevent tissues from functioning properly, break down membranes and inhibit production of DNA, RNA and proteins.
- Producing toxins. Most bacterial pathogens produce toxins.
Data and disease
Epidemiology is the study of the incidence and pattern of a disease with a view to finding the means of preventing and controlling it. To do this, epidemiologists collect data on diseases and then look for a pattern or relationship between these diseases and various factors in the lives of people who have them.
A correlation occurs when a change in one of two variables is reflected by a change in the other variable.
We need experimental evidence to prove a causal connection.
Lifestyle and health
Risk is a measure of the probability that damage to health will occur as a result of a given hazard.
The concept of risk has two elements:
- The probability that a hazardous event will occur
- The consequences of that hazardous event
Risk is measured by comparing the likelihood of harm occurring in those exposed to a hazard with those who are not exposed to it, e.g. smokers may be 15 times more likely to develop lung cancer than non-smokers.
Lifestyle factors contributing to cancer: smoking, diet, obesity, physical activity, and sunlight.
Lifestyle factors contributing to coronary heart disease: smoking, high blood pressure, blood cholesterol levels, obesity, diet, and physical activity.
Enzymes and the digestive system
Glands of the digestive system produce enzymes, which break down large molecules into small ones ready for absorption.
Digestion takes place in two stages:
1. Physical breakdown: if food is large it is broken down into smaller pieces by structures such as the teeth. This makes ingestion of food possible and provides a large surface area for chemical digestion. Food is churned by muscles in the stomach wall, which physically breaks it up.
2. Chemical breakdown: breaks down large, insoluble molecules into smaller, soluble ones. It is carried out by enzymes, which function by hydrolysis (splitting up molecules by adding water to the chemical bonds that hold them together).
- Carbohydrases break down carbohydrates to monosaccharides
- Lipases break down lipids into glycerol and fatty acids
- Proteases break down proteins into amino acids
These molecules are absorbed from the small intestine into the blood and carried to different parts of the body.
Major parts of the digestive system
- The oesophagus; carries food from mouth to stomach, adapted for transport.
- The stomach; stores and digests food, enzymes produced by glands to digest protein, glands in inner wall produce mucus to stop the stomach from digesting itself.
- The small intestine; further digests food with enzymes produces by walls and by glands that pour their secretions in, and absorbs product of digestion, inner walls folded into villi and microvilli for increased surface area.
- The large intestine; absorbs water, much of which is reabsorbed from secretions of digestive glands.
- The salivary glands; secretions passed via duct into mouth containing amylase, which breaks down starch into maltose.
- The pancreas; gland below stomach, produces pancreatic juice which contains proteases, lipase, and amylase to digest starch.
Carbohydrates - Monosaccharides
Basic monomer unit of carbohydrates: sugar / saccharide / monosaccharide
Two units: disaccharide, many units: polysaccharide.
Monosaccharides are sweet tasting, soluble substances with the general formula (CH2O)n. The most well known monosaccharide is glucose, with the formula C6H12O6.
Test for reducing sugar
Reduction is a chemical reaction involving gain of electrons. Reducing sugars are sugars that can donate an electron to another chemical, in this case Benedict's reagent.
- Add liquid food sample to test tube.
- Add equal volume of Benedict's reagent, an alkaline solution of copper (II) sulfate.
- Heat mixture in a gently boiling water bath for 5 minutes.
- If a reducing sugar is present, an insoluble red precipitate of copper (I) oxide is formed.
This colour change takes place because sugar donates electrons that reduce blue copper (II) sulfate to orange copper (I) oxide.
Carbohydrates - Disaccharides and polysaccharides
When combined in pairs, monosaccharides form a disaccharide. For example:
- Glucose + glucose → maltose
- Glucose + fructose → sucrose
- Glucose + galactose → lactose
A molecule of water is removed in the joining of two monosaccharides, in a condensation reaction. The bond formed is a glycosidic bond. The opposite reaction, splitting up two or more monosaccharides by adding a water molecule is called hydrolysis.
Polysaccharides are polymers, formed by combining together many monosaccharide molecules with glycosidic bonds formed by condensation reactions. Polysaccharides are very large molecules, so they are insoluble. This feature makes them suitable for storage. Some polysaccharides, such as cellulose, are not used for storage but give structural support for plant cells.
Starch is a polysaccharide that is found in many parts of plants in the form of small granules or grains, e.g. starch grains in chloroplasts. It is formed by the linking of between 200 and 100 000 glucose molecules.
Test for non-reducing sugars
Some disaccharides, such as sucrose, are non-reducing sugars and do not change the colour of Benedict's reagent. In order to detect a non reducing sugar it must first be broken down into it's monosaccharide components by hydrolysis.
- Benedict's test - sample remains blue.
- Add another food sample to dilute hydrochloric acid and place test tube in gently boiling water bath for 5 minutes. This hydrolyses any disaccharides present.
- Add sodium hydrogencarbonate solution to test tube to neutralise the hydrochloric acid.
- Re-test the resulting solution with Benedict's reagent in a gently boiling water bath for 5v minutes/
- If a non reducing sugar was present in the original sample, the Benedict's reagent will turn orange-brown.
This colour change is due to the reducing sugars produced from the hydrolysis of the non-reducing sugar.
Test for starch
Starch is easily detected by it's ability to change the colour of the iodine in potassium iodide solution from yellow to blue-black. The test is carried out at room temperature.
- Place sample to be tested into a test tube or spotting tile.
- Add two drops of iodine solution and shake or stir.
- The presence of starch is indicated by a blue-black coloration.
Starch → maltose → glucose
Enzymes involved in the digestion of carbohydrates:
- Amylase breaks down starch
- Maltase breaks down maltose
- Sucrase breaks down sucrose
- Lactase breaks down lactose
Basic monomer units - amino acids
Polymers - polypeptide (which can be combined to form proteins)
- Amino group (-NH2)
- Carboxyl group (-COOH)
- Hydrogen atom (-H)
- R group: each amino acid has a different R group.
- Primary structure - Joining of many amino acids into a polypeptide chain - polymerisation. There are 20 naturally occurring amino acids.
- Secondary structure - -NH and -C=O groups form weak hydrogen bonds together. This causes the chain to form a 3D shape (alpha-helix, beta-pleated sheet)
- Tertiary structure - Further folding, involving disulphide bonds, ionic bonds and hydrogen bonds.
- Quaternary structure - Many polypeptide chains join together to form a protein. Additional prosthetic groups (non-protein components).
Test for proteins
The most reliable test for proteins is the biuret test, which detects peptide links.
- Place sample in test tube and add sodium hydroxide solution at room temperature.
- Add a few drops of dilute (0.05%) copper (II) sulfate solution and mix gently.
- A purple coloration indicates the presence of peptide bonds and hence a protein. If no protein is present, the solution remains blue.
Enzymes are globular proteins that act as catalysts. Catalysts alter the rate of a chemical reaction without undergoing permanent changes themselves. They can therefore be reused. Enzymes lower activation energy of chemical reactions.
Despite their large size, only a small region is functional: the active site. This forms a small hollow depression which substrate fits into, forming an enzyme-substrate complex.
Lock and key model - enzymes and substrates are complimentary in shape, and a substrate fits only into the active site of a particular enzyme. Enzymes are rigid structures.
+ Enzymes are specific in the reactions they catalyse
- Molecules could bind to other sites and alter activity of enzyme - not rigid, flexible!
Induced fit model - Enzymes are flexible and can mould themselves to the shape of the substrate. They have a general shape which alters in the presence of a substrate. As it changes shape it puts a strain on the substrate molecule which distorts a particular bond and lowers activation energy needed to break that bond.
+ Can explain how other molecules affect enzyme activity and lowering of activation energy.
Factors effecting enzyme action
For an enzyme to work it must come into physical contact with it's substrate and have an active site which fits it's substrate. Factors influencing enzyme activity normally affect one or both of these.
- Temperature - rise in temperature = rise in kinetic energy of molecules. This means more movement, and an increased likelihood of collisions between enzyme and substrate. However, very high temperatures can break bonds within the enzyme. This changes the shape of the enzyme and active site. Eventually the enzyme is disrupted so much that is stops working, and is denatured.
- pH - a change in pH alters the charges on the amino acids that make up the active site of the enzyme. As a result, the substrate can no longer become attached to the active site and so the enzyme-substrate complex cannot be formed. A change in pH can also cause bonds that maintain the enzyme's tertiary structure to break. The enzyme therefore changes shape. These changes can alter the shape of the active site and the substrate may therefore no longer fit it. The enzyme has been denatured.
- Substrate concentration - Low substrate concentration means active sites of enzymes are not working to full capacity. When all active sites are occupied the rate of reaction is at it's maximum. Excess of substrate has no further impact.
Inhibitors are substances that directly or indirectly interfere with the functioning of the active site of an enzyme and reduce it's activity. There are two types:
- Competitive inhibitors - they have a molecular shape similar to that of the substrate. This allows them to occupy the active site of an enzyme, and therefore compete with the substrate for the available active sites.
- Non-competitive inhibitors - they attach themselves to the enzyme at a site which is not the active site. Upon attaching to the enzyme, the inhibitor alters the shape of the enzyme's active site in such a way that the substrate molecules can no longer occupy it, and so the enzyme cannot function.
Magnification = size of image / size of object
Magnification - how many times bigger the image is that the object.
Resolution - the minimum distance two objects can be apart and still be perceived as separate objects rather than one object. Relates to clarity of image.
Light microscopes have a resolution of 0.2um, electron microscopes have a resolution of 0.1nm.
Process in which cells are broken up and different organelles are separated out.
Solution is cold - to reduce enzyme activity that may break down organelles, isotonic - to prevent organelles bursting or shrinking as a result of osmotic gain or loss of water, and buffered - to maintain a constant pH.
Two stages of cell fractionation:
- Homogenation - cells are broken up by a homogeniser. This releases the organelles from the cell. The homogenate is then filtered to remove complete cells and large debris.
- Ultracentrifugation - the tube of filtrate is placed in the ultracentrifuge and spun at a slow speed. The heaviest organelles, the nuclei, are forced to the bottom of the tube and form a thin sediment or pellet. The supernatant is removed, leaving just the sediment. The supernatant is transferred to another tube and spun at a faster speed. The next heaviest organelles are forced to the bottom of the tube. This process is continued.
Nuclei → mitochondria → lysosomes → ribosomes
Transmission electron microscope - used to view a cross-section of a specimen. Resolving power of 0.1nm.
Scanning electron microscope - used to view surface / shape of a specimen. Resolving power of 20nm.
Pros / cons of electron microscopes:
- High resolving power - electrons have a shorter wavelength than light
- Beam can be focused using electromagnets
- No living specimens observed - system must be in a vacuum
- Complex staining process required to prepare specimen, only producing black and white image
- Specimen must be extremely thin (only applies to TEM)
- Image may contain artefacts
Structure of epithelial cells
Nucleus - control centre, retains genetic material, produces RNA, hence protein synthesis
- Nuclear envelope - membrane surrounding nucleus, continuous with endoplasmic reticulum
- Nuclear pores - allow passage of molecules
- Nucleoplasm - granular, jelly-like material
- Chromatin - DNA found within nucleoplasm
- Nucleolus - small, spherical body within nucleoplasm. Manufactures ribosomal RNA and assembles ribosomes
Mitochondrion - produce ATP from carbohydrates
- Double membrane - outer controlling entry and exit, inner folding to form cristae
- Cristae - shelf-like extensions, providing large surface area for attachment of enzymes involved in respiration
- Matric - makes up remainder of mitochondrion
Structure of epithelial cells 2
Endoplasmic reticulum - continuous with outer nuclear membrane. Two types:
- Rough endoplasmic reticulum - ribosomes present on outer surface. Function is to provide large surface area for the synthesis of proteins and glycoproteins, and provide a pathway for the transport of materials throughout the cell.
- Smooth endoplasmic reticulum - lacks ribosomes on surface. Function is to synthesise, store and transport lipids and carbohydrates.
Golgi apparatus - proteins and lipids from ER passed to GA which modifies and labels them for transport in vesicles to cell surface.
Ribosomes - small cytoplasmic granules. Important in protein synthesis.
Microvilli - finger-like projections of the epithelial cell that increase it's surface area to allow more efficient absorption.
Insoluble in water, soluble in organic solvents, containing carbon, hydrogen and oxygen.
Main role in in plasma membranes. Other roles include energy, waterproofing, insulation and protection.
- Hydrophilic head which interacts with water
- Hydrophobic tail which orients itself away from water but mixes readily with fat
Test for lipids
The emulsion test:
- Put sample to be tested in a dry test tube
- Add ethanol
- Shake thoroughly to dissolve lipid in sample
- Add water and shake gently
- A cloudy-white colour indicated presence of lipid
The cloudy colour is due to any lipid in the sample being finely dispersed in the water to form an emulsion.
The cell-surface membrane
Membrane surrounding cells, forming a barrier between the cell cytoplasm and environment. Allows different conditions inside and outside of cell and controls movement of substances.
Formed of a double layer of phospholipids, which have their hydrophilic heads facing the environment outside of the cell, and the cytoplasm inside of the cell. Their hydrophobic tails face each other, forming the centre of the membrane.
Phospholipids allow lipid-soluble substances to enter and leave the cell, prevent water from doing so, and make the membrane flexible.
The membrane contains proteins. Extrinsic proteins on the surface or partially embedded provide mechanical support and act as hormone receptors. Intrinsic proteins span the membrane completely and act as carriers to transport water-soluble material or as enzymes.
The structure of the cell-surface membrane is called the fluid-mosaic model. Fluid as phospholipids are free to move relative to one another, meaning the membrane is flexible, and mosaic because proteins in the membrane vary in size and shape, like the tiles of a mosaic.
The net movement of molecules or ions from an area of high concentration to an area of low concentration.
Factors affecting diffusion are:
- Concentration gradient
- Area over which diffusion takes place (surface area)
- Thickness of exchange surface
Diffusion = (surface area x difference in concentration) / length of diffusion path
Facilitated diffusion is diffusion involving the presence of protein carrier molecules to allow the passive movement of substances across plasma membranes.
The passage of water from a region where it has a higher water potential to a region where it has a lower water potential through a partially permeable membrane.
Pure water under standard conditions has a water potential of zero. All other values of water potential are negative.
Allows cells to exchange molecules against a concentration gradient. Metabolic energy is required.
The movement of molecules or ions into or out of a cell from a region of lower concentration to a region of higher concentration using energy and carrier molecules.
Energy in the form of ATP is used.
Carrier protein molecules which act as 'pumps' are involved.
The process is very selective.
Absorption in the small intestine
Glucose is absorbed though the walls of the small intestine, which are folded into villi.
- Villi increase the surface area for diffusion.
- They are very thin walled, thus reducing the distance over which diffusion takes place.
- They are able to move and help maintain a diffusion gradient.
- They are well supplied with blood vessels so blood can carry away absorbed molecules and maintain a diffusion gradient.
Diffusion is involved in the absorption of glucose into the blood. However, active transport is also used to transport all of the glucose in the lumen of the intestine.
Sodium is actively transported out of epithelial cells into the blood. There is therefore a higher concentration of sodium in the intestine than inside the epithelial cells. Sodium moves into epithelial cells due to the concentration gradient through a co-transport protein. They couple with glucose molecules which are also carried into the cell.
Prokaryotic / eukaryotic cells
Prokaryotic cells have no true nucleus, only diffuse area of nuclear material. Eukaryotic cells have a distinct nucleus with nuclear envelope.
Prokaryotic cells have no nucleolus, where eukaryotic cells do.
Prokaryotic cells have circular strands of DNA. Eukaryotic cells have chromosomes where DNA is located.
Prokaryotic cells have no membrane-bounded organelles. Eukaryotic cells have membrane-bounded organelles such a mitochondria.
Prokaryotic cells have no chloroplasts, which are present in eukaryotic cells of plants and algae.
Ribosomes are smaller in prokaryotic cells than eukaryotic cells.
Cell walls in prokaryotic cells are made of peptidoglycan. Where present in eukaryotic cells. the cell wall is made mostly of cellulose.
Oral rehydration therapy
Diarrhoea is caused by damage to epithelial cells of the intestine, loss of microvilli due to toxins and excessive secretion of water due to toxins.
To treat diarrhoeal diseases, we use a rehydration solution. It must contain:
- Water - to rehydrate tissues
- Sodium - to replace sodium lost and make use of sodium-glucose carrier proteins
- Glucose - to stimulate uptake of sodium and provide energy
- Potassium - to replace potassium lost and stimulate appetite
- Other electrolytes - to prevent electrolyte imbalance
These ingredients can be packaged as a powder, which can be made into a solution with boiled water as needed and administered with minimal training.
The solution should be taken regularly in large amounts throughout the illness.
Structure of the human gas-exchange system
- The lungs; lobed structures made of series of highly branched tubules, called bronchioles, which end in tiny air sacs called alveoli.
- The trachea; flexible airway supported bu rings of cartilage. Lined with ciliated epithelium and goblet cells which produce mucus that traps dirt and bacteria.
- The bronchi; two divisions of the trachea, each leading to one lung. Similar in structure to trachea.
- The bronchioles; a series of branching subdivisions of the bronchi.
- The alveoli; minute air sacs at the end of bronchioles. The alveolar membrane is the gas-exchange surface.
The mechanism of breathing
The process of breathing in and out is called ventilation.
Atmospheric air pressure > air pressure in lungs → inspiration
- External intercostal muscles contract, so ribs are pulled upwards and outwards, increasing the volume of the thorax.
- Diaphragm muscles contract and flatten, also increasing volume of the thorax.
- Increased volume results in reduced pressure in the lungs.
- Atmospheric pressure is now greater that pulmonary, so air is forced into lungs.
Atmospheric air pressure < air pressure in lungs → expiration (passive)
- Internal intercostal muscles contract, so ribs move downwards and inwards, decreasing the volume of the thorax.
- The diaphragm muscles relax, decreasing volume of thorax further.
- Decreased volume increases pressure in the lungs.
- Pulmonary pressure is now greater than atmospheric, so air is forced out of the lungs.
Pulmonary ventilation = tidal volume x ventilation rate
Exchange of gases in the lungs
Essential features of exchange surfaces:
- Large surface area to volume ratio
- Very thin
- Partially permeable
- Movement of the environmental medium
- Movement of the internal medium
Alveoli are essential in gas exchange. Each alveolus is lined with epithelial cells and surrounded by a dense capillary network. Diffusion of gases is very quick because:
- Red blood cells are slowed as they pass through capillaries, allowing more time for diffusion
- Red blood cells are flattened against capillary walls, so there is a reduced distance to alveloar air
- The walls of alveoli and capillaries are very thin
- Alveoli and capillaries have a large total surface area
- Steep concentration gradient maintained by movement of internal and external medium
Caused by rod-shaped bacteria, mycobacterium tuberculosis.
Symptoms include a persistent cough, tiredness, loss of appetite leading to weight loss, fever and eventually coughing up blood.
Once the bacterium gains entry to the body...
- The bacteria grow and divide in upper regions of lungs.
- The body's immune system responds and white blood cells accumulate at site of infection to ingest bacteria
- This leads to inflammation and enlargement of the lymph nodes that drain that area of the lungs. This is primary infection, usually occurring in children. Few bacteria remain.
- Many years later, bacteria may re-emerge as a secondary infection; post-primary tuberculosis.
- This time bacteria are not so easily controlled and destroy the tissue of the lungs, resulting in cavities and scar tissue.
- The sufferer coughs up damaged lung tissue and blood. Without treatment this can spread to the rest of the body, and be fatal.
People most at risk of TB
- People in close contact with infected individuals for long periods of time.
- People who work or reside in care facilities where many people live close together, e.g. care homes, prisons, hospitals.
- People from countries where TB is common.
- People who have reduced immunity
- The very young or very old
- Those with AIDS
- People with other medical conditions that make the body less able to resist disease, such as diabetes
- Those undergoing treatment with immunosuppressant drugs
- The malnourished
- Alcoholics or injecting drug-users
- The homeless
Arises when scars form on the epithelium of the lungs, causing them to thicken. Oxygen cannot diffuse into the blood as efficiently due to a lengthened diffusion pathway, and volume of air that the lungs can contain is reduced.
Fibrosis also reduces elasticity of the lungs; it is then harder to breathe out and ventilate the lungs.
Effects of fibrosis on lung functions:
- Shortness of breath, especially when exercising, due to a considerable volume of air space within lungs being occupied by fibrous tissue. Also due to thickened epithelium and lack of elasticity.
- Chronic, dry cough due to fibrous tissue providing an obstruction in the airways that the body tries to remove by coughing.
- Pain and discomfort in the chest because of pressure and damage from the mass of fibrous tissue in the lungs.
- Weakness and fatigue because of reduces intake of oxygen in the blood, meaning reduced release of energy by cellular respiration.
Evidence suggests fibrosis is a response to microscopic lung injury.
Asthma is a localised allergic reaction. Some allergens affecting asthma are pollen, animal fur and dust. Common triggers are air pollutants, exercise, cold air, infection, anxiety and stress. These allergens cause white blood cells on the linings of the bronchi and bronchioles to release a chemical called histamine.
- The linings of these airways becomes inflamed.
- The cells of the epithelial lining secrete larger quantities of mucus than usual.
- Fluid leaves the capillaries and enters the airways.
- The muscle surrounding the bronchioles contracts and so constricts the airways.
There is a greater overall resistance to airflow. The symptoms are:
- Difficulty breathing
- A wheezing sound when breathing
- A tight feeling in the chest
One in five smokers develop emphysema. In people with emphysema, the elastin of the lungs becomes permanently stretched and the lungs are no longer able to forge out air from the alveoli. The surface area of the alveoli is reduces and they sometimes burst. Little exchange of gasses can take place on stretched and damaged air sacs.
Symptoms of emphysema:
- Shortness of breath due to difficulties in exhaling air due to loss of elasticity in lungs. It is difficult to then inhale fresh air containing oxygen and so the patient feels breathless.
- Chronic cough is the body's effort to remove damaged tissue and mucus that cannot be removed naturally because cilia on bronchi and bronchioles have been destroyed.
- Bluish skin coloration due to low levels of oxygen in the blood.
The only way to minimise risk of emphysema is to not smoke at all / give up smoking.
The structure of the heart
- The atrium is thin walled and elastic and stretches as it collects blood. It only has to pump blood the short distance to the ventricle and therefore has only a thin muscular wall.
- The ventricle has a much thicker muscular wall as it has to pump blood some distance, either to the lungs or to the rest of the body.
Between the atrium and the ventricle are valves that prevent back flow of blood into the atria when the ventricles contract:
- The left atrioventricular (bicuspid) valves, on the left side of the heart.
- The right atrioventricular (tricuspid) valves, on the right side of the heart.
Vessels connected to the four chambers of the heart:
- The aorta is connected to the left ventricle and carries oxygenated blood to all of the body.
- The vena cava is connected to the right atrium and brings deoxygenated blood back from the tissues of the body.
- The pulmonary artery is connected to the right ventricle and carries deoxygenated blood to the lungs.
- The pulmonary vein is connected to the right atrium and being oxygenated blood back from the lungs.
The cardiac cycle
There are two phases to the beating of the heart: contraction (systole) and relaxation (diastole).
Blood returns to the atria through the pulmonary vein and vena cava. Atria fill and pressure rises, opening the atrioventricular valves and allowing blood to pass into the ventricles. Relaxation of muscular walls reduces pressure in ventricle, so it is lower than in the aorta and pulmonary artery and so the semi-lunar valves in the aorta and pulmonary artery close.
Atrial and ventricular systole:
Muscle of atrial wall contracts, forcing blood into ventricles. Short delay to allow ventricles to fill with blood, then simultaneous contraction. This increases the blood pressure and forces shut the atrioventricular valves, preventing back flow. The pressure forces open the semi-lunar valves, pushing blood into the pulmonary artery and aorta. Walls of the ventricles are thicker as they have to pump blood a further distance.
Control of the cardiac cycle
Cardiac cycle - myogenic (contraction initiated from within muscle)
- Electric impulse from sinoatrial node (SAN) across both atria, causing contraction.
- Layer of non-conductive tissue, atrioventricular septum, prevents wave crossing into ventricles.
- Wave of electrical activity allowed to pass through atrioventricular node (AVN).
- After a short delay, the AVN conveys electrical wave between ventricles along muscle fibres called the bundle of His.
- Bundle of His conducts wave through atrioventricular septum to base of ventricles, where the bundle branches into smaller fibres.
- Wave of electrical activity released from these fibres, causing ventricles to contract simultaneously from the apex of the heart upwards.
Coronary heart disease (CHD)
Atheroma: a fatty deposit that forms in the wall of an artery. Begins as fatty streaks of white blood cells that have taken up low-density lipoproteins. These streaks enlarge to form an atheromatous plaque. Commonly occur in large arteries, made up of deposits of cholesterol, fibres and dead muscle cells. They bulge in the lumen of the artery, reducing blood flow. Atheromas increase the risk of thrombosis and aneurysm.
Thrombosis: if atheroma bursts through the endothelium of the blood vessel, it forms a rough surface that interrupts the smooth flow of blood. This may result in the formation of a blood clot or thrombus. The thrombus may reduce or prevent the flow of blood to tissues beyond it. The region of tissue deprived of blood often dies, and a thrombus can be carried from it's place of origin and block another artery.
Aneurysm: atheromas leading to thrombus also weaken the artery walls. The weakened points swell to form a balloon-like, blood filled structure called an aneurysm. They frequently burst, leading to haemorrhage and loss of blood to the region of the body served by that artery.
Myocardial infarction: heart attack, referring to reduced supply of oxygen to the muscle of the heart. Results from blockage in coronary arteries. If the blockage is close to the aorta, the heart will stop beating all together. If it is further away, symptoms will be milder, because a smaller area of muscle will suffer oxygen deprivation.
Risk factors: smoking, high blood pressure, blood cholesterol and diet.
Immunity - defence mechanisms
Two types of defence mechanisms:
- Non-specific mechanisms do not distinguish between pathogens and respond rapidly to all of them in the same way. Two types of mechanisms:
- A barrier to the entry of pathogens
- Specific mechanisms distinguish between pathogens. They act less rapidly but provide long-lasting immunity. Response involves a white blood cell called a lymphocyte, taking two forms:
- Cell mediated responses involving T lymphocytes
- Humoral responses involving B lymphocytes
Barriers to entry
- A protective covering - the skin provides a physical barrier that most pathogens find hard to penetrate.
- Epithelia covered in mucus - pathogens stick to mucus in the lungs which is transported away by cilia, up the trachea.
- Hydrochloric acid in the stomach - provides a low pH which denatures enzymes on most pathogens which are therefore killed.
Chemical products of pathogen act as attractants, causing phagocytes to move towards the pathogen.
- Phagocytes attach themselves to the surface of the pathogen.
- They engulf the pathogen to form a vesicle, known as a phagosome.
- Lysosomes move towards the vesicle and fuse with it.
- Enzymes within lysosomes break down the pathogen in the same process as that for the digestion of the food in the intestines.
- The soluble products from the breakdown of the pathogen are absorbed into the cytoplasm of the phagocyte.
Phagocytosis causes inflammation at the site of infection. The swollen area contains dead pathogens and phagocytes. Inflammation is the result of the release of histamine, which causes dilation of the blood vessels.
T-lymphocytes respond to an organism's own cells that have been invaded by non-self material. They can distinguish these cells from normal cells because phagocytes present some of the pathogen's antigens on their own cell-surface membranes, as do body cells with viral antigens and cancer cells. These are antigen-presenting cells.
- Pathogens invade body cells or are taken in by phagocytosis.
- Phagocytes place antigens from pathogens on cell-surface membrane.
- Receptors on certain T-helper cells fit exactly onto these antigens.
- This activates other T cells to divide rapidly by mitosis and form a clone.
- The cloned T cells:
- Develop into memory cells that enable a rapid response to future infections by the same pathogen
- Stimulate phagocytes to engulf pathogens
- Stimulate B cells to divide
- Kill infected cells
- The T cells produce perforin, a protein that forms pores in the target cell's membranes allowing water and ions in, causing lysis/bursting of the cell.
- The surface antigens of invading pathogens are taken up by B cells.
- B cells process antigens and present them on their surfaces.
- T helper cells activated in cell mediated immunity attach to processed antigens on B cells, activating them.
- B cells are activated to divide by mitosis and give a clone of plasma cells.
- Cloned plasma cells produce antibodies that fit the antigens on the pathogens surface.
- Antibodies attach to antigens on the pathogen and destroy them. This is the primary immune response.
- Neutralisation: antibodies bind to the antigens on the pathogen's membrane and prevent it from attaching to and entering host cells. The antibodies encourage macrophages to phagocytose the pathogen.
- Agglutination: antibodies bind to antigens on the surface of several pathogens, clumping them together. Macrophages can then recognise and easily destroy the pathogen by phagocytosis.
- Some B cells develop into memory cells that can respond to future infections of the same pathogen by rapidly dividing and developing into plasma cells that produce antibodies. This is the secondary immune response.
Antibodies are proteins synthesised by B cells. Antibodies bind to antigens precisely, in the same way a key fits a lock. They are therefore very specific.
They are made up of four polypeptide chains. One pair of chains are long and called heavy chains. The other pair are shorter and called light chains.
To fit around antigens, they are Y shaped and can move as if they have a hinge at the fork of the Y shape. Antibodies have a binding site that fits precisely onto the antigen to form an antigen-antibody complex.
The binding site is called the variable region. The rest of the antibody is the same in all antibodies and called the constant region. This binds to receptors on cells such as B cells.
Monoclonal antibody production
Polyclonal antibodies are naturally produced in an immune response. There are a variety of antibodies produces with a variety of antigen binding sites. Monoclonal antibodies are produces from clones of a single plasma cell and are all identical. They are produced in this way:
- Immunization of mouse to stimulate antibody production
- Antibody-forming cells isolated from spleen
- Tumor cells are grown in tissue culture
- Antibody-forming cells are fused with cultivated tumor cells to form hybridomas
- Fused cells screened for antibody production
- Antibody-producing hybridomas are cloned
- Monoclonal antibodies isolated for cultivation