3.3.4 Mass transport

Okay so firstly we should look at why we have mass transport. Luckily for us I already covered it here: 3.3.1

Basically what i'm saying is that many cells in multicellular organisms are too far from exchange surfaces to exchange materials by diffusion/active transport alone. To solve this problem, cells of multicellular organisms bathe in tissue fluid (tissue fluid is the environment around the cells). When absorbed, materials are distributed throughout the tissue fluid so cells can absorb them. Example materials include nutrients (e.g fatty acids, amino acids, glucose, minerals, vitamins), gases (respirator gases, oxygen and carbon dioxide), heat, and urea (and other excretory products). Diffusion is enough to transport materials over short distances but the efficient supply of materials over a large(r) distance requires a mass transport system.

This is because with increasing size the surface area to volume ratio decreases (read this). Eventually the surface area to volume ratio decreases so much that diffusion/active transport alone can no longer support the organism. A transport system is required to take materials to/from the specialised exchange surfaces. Materials must be transported between exchange surfaces/external environment/internal environment/cells etc etc. As organisms get bigger the issues and organs they have have become more developed and specialised and also more dependant on each other making a transport system essential.

Transport systems should have certain features to be 'good'. These include:

• A suitable medium to carry materials (e.g we have blood) - usually liquid based as most substances can dissolve in water and can be moved around easily. We also have air for gas exchange
• Form of mass transport in which the medium is moved around (e.g ventilation/movement of blood)
• Closed system of vessels containing the transport medium to transport the transport medium to all of the organism
• A mechanism for moving the transport medium - a pressure gradient (e.g our heart creates a pressure gradient that moves the blood around, contraction of muscles in the tracheae moves air in an insect, evaporation of water (plants).

Mammals have a closed double circulatory system. This means blood passes twice through the heart. This is because when it goes to the lungs it loses pressure so it must go through the heart once again to have enough pressure to be pumped around the body - if it were to pass straight from the lungs to around the body circulation would be pretty slow and some cells would die (yikes). It is necessary for materials to be delivered/removed to/from he body quickly as mammals have a high body temperature and therefore a high metabolic rate. Once the  materials enter the tissue fluid they enter cells by diffusion. 

Ta dah.

3.3.3 Digestion and absorption

EDIT: Hi guys, I was just going through the blog and I CANNOT work out why the formatting on this post is so strange (the text keeps coming up as different fonts/colours) -  I wrote it all at the same time so I don't see why this is happening. I've tried to resolve but with no luck, sorry:(


Glands in the human digestive system produce enzymes to hydrolyse large insoluble molecules into smaller soluble ones so they can be absorbed. We don’t distinctly need to know the main parts of our digestive system, but nonetheless it may help for understanding so here goes:

• Salivary gland: situated near mouth to hydrolyse starch into maltose with silvery amylase contained in their secretions
• Oesophagus: carries food from mouth to stomach
• Stomach: muscular sac with inner layer producing enzymes. Stores and digests food (particularly proteins)
• Pancreas: large gland situated below the stomach whose secretions contain proteases lipase and amylase
• Ileum (small intestine): produces enzymes in its walls to further digest food. Inner walls folded into villi with microvilli to increase surface area for absorption
• Duodenum (large intestine): absorbs water
• Rectum: faeces stored here before being periodically removed via the anus (digestion)

Digestion occurs in two stages: physical breakdown and then chemical digestion.

Physical breakdown is basically the physical breakdown of food (duh). Large food is broken down into smaller pieces by teeth/stomach providing a larger surface area for chemical digestion.

Chemical digestion is the hydrolysis of large insoluble molecules into smaller soluble molecules carried out by enzymes. More than one enzyme is required to hydrolyse a large molecule as enzymes are specific. The different types of digestion are as follows:

• Carbohydrate digestion: Salivary amylase is produced in the mouth. This hydrolyses alternate starch glycosidic bonds forming lots of maltose disaccharides. Mineral salts in the saliva maintain a neutral pH. The food is swallowed and enters the stomach. pH2 in the stomach denatures the salivary amylase. Food is passed into the ileum and mixed with pancreatic amylase (amylase produced in the pancreas) - this hydrolyses any remaining starch into maltose. Alkaline salts produced by the ileum and pancreas maintain a neutral pH. The epithelial lining of the ileum produces maltase (a membrane bound disaccharidase) which hydrolyses the maltose into alpha glucose.
• Also: sucrase (a membrane bound disaccharidase) hydrolyses sucrose producing glucose and fructose. Lactase (a membrane bound disaccharidase) hydrolyses lactase producing glucose and galactose
• Lipid digestion: Lipids are hydrolysed my lipases. These are produced in the pancreas and hydrolyse the ester bond in triglycerides to produce two fatty acids and a monoglyceride. Firstly, lipids are split up by bile salts (produced by the liver). Monoglycerides and fatty acids remain in association with these bile salts forming micelles - a process known as emulsification which increases the surface area. They do not stick to each other (forming large micelles) as the bile salts arrange themselves with their lipophilic ends in fat droplets and their lipophobic ends sticking out. When the micelles come into contact with the villi (on the ileum lining) they break down releasing the constituent monoglycerides and fatty acids (both of thee are non-polar so can easily diffuse across the cell surface membrane into the epithelial cells that line the ileum). Once inside, monoglycerides and fatty acids are transported to the endoplasmic reticulum where they recombine to form triglycerides. Here and in the Golgi apparatus/body they associate with cholesterol and lipoproteins forming chylomicrons which move out of the epithelial cells by exocytosis and enter lacteals (lymphatic capillaries). From here they pass into the blood system. Triglycerides in chylomicrons are hydrolysed by an enzyme in the endothelial cell of the capillaries.
• Protein digestion: peptidases (also known as proteases) hydrolyse proteins as follows...
• Endopeptidases hydrolyse peptide bonds in the central region of a protein molecule - this forms a load of peptide molecules
• Exopeptidases hydrolyse peptide bonds on the terminal amino acids releasing single amino acids and dipeptides
• Dipeptidases (membrane bound to the ileum) hydrolyse peptide bonds in dipeptides

The digestion of proteins and carbohydrates produces amino acids and monosaccharides respectively. These are absorbed into the bloodstream in the ileum by co-transport.

NOTE: It might get a bit confusing that ENDopeptidases don't hydrolyse the END peptide bonds...sorry don't have any help for this just try not to get confused lol

So, you've heard a lot about the ileum, but what actually is it? It is a long tube whose inner wall is folded forming finger like projections (villi). They have thin walls that are lined with epithelial cells and on the other side is a network of capillaries meaning it ha a rich blood supply. Villi accelerate the rate of absorption because...

• Increase the surface area for diffusion
• Contain muscle therefore are able to move the exchange medium ensuring a concentration gradient is established/maintained
• Well supplied with blood vessels maintain a diffusion gradient
• Thin walled - decreasing the diffusion distance
• Possess microvilli further increasing the surface area for absorption

3.3.2: Gas exchange (The human gas exchange system)

Okay we are *almost* done with gas exchange.

Mammals must absorb/remove a large volume of oxygen/carbon dioxide, respectively, because they are relatively large organisms with a large volume of living cells and they have to maintain a high body temperature which relates to them having high metabolic and respiratory rates.

First off, we need to know a bit about how much air is taken in/out of the lungs in a given time. This is the pulmonary ventilation rate and can be calculated using the equation…

pulmonary ventilation rate = tidal volume x breathing rate

Tidal volume is the volume of air normally taken in at each breath when the body is at rest

Breathing/ventilation rate is the number of breaths taken in one minute

The lungs are the site of gas exchange in humans. They are situated inside the body as air is not dense enough to support/protect them (they are very delicate) and also the body would lose a large amount of water/dry out. The structure of the lungs is as follows:

• The trachea: flexible airway supported by cartilage rings (similar to insect tracheae). The cartilage prevents collapse when pressure decreases when breathing in. Walls are made of muscle lined with goblet cells and ciliated epithelium. Produce mucus to trap dirt
• Bronchi: two divisions of the trachea. Produce mucus to trap dirt but do not contain cartilage all the way along them. Are also ciliated to move dirt particles to the throat
• Bronchioles: series of branching divisions of the bronchi. Walls made of muscle  which can constrict to control how of air in/out of alveoli
• Alveoli: air sacs at the end of bronchioles. Between them is are some collagen and elastic fibres. Elastic fires allow them to stretch and recoil during inhalation/exhalation respectively to expel co2 rich air. This is the gas exchange surface. Lined with epithelium. Around each alveolus is a network of capillaries. Red blood cells are slowed and flattened against the capillary walls, increasing the time for diffusion and decreasing the diffusion distance.

Yeah, that makes sense, but how does the air actually get in and out of the lungs?

To maintain a diffusion gradient, air is constantly moved in and out of the lungs (ventilation). When air pressure in the lungs exceeds atmospheric air pressure air is forced out of the lungs (expiration/exhalation). When air pressure of the atmosphere is greater than air pressure inside the lungs, air is forced into the lungs. These pressure changes are as a result of certain muscles. Inspiration:

• Diaphragm contracts, increases the thorax volume
• External intercostal muscles contract
• Internal intercostal muscles relax
• Ribs are pulled up and out
• Increased thorax volume decreases lung pressure

Expiration:

• Diaphragm relaxes, decreasing the thorax volume
• External intercostal muscles relax
• Internal intercostal muscles contract
• Ribs move inward and down
• Decreased thorax volume increases lung pressure

NOTE: I find it SO hard to remember which of the intercostal muscles relax/contract for inhalation/exhalation - if anyone has a way of remembering it please let me know (in the comments??)!!

NOTE 2.0: During normal breathing it is the recoil of alveolar elastic tissue which mainly forces the air out. Strenuous exercise causes various muscles to play a part so gases are exchanged faster = more oxygen in = more respiration = more ATP = less anaerobic respiration/reduced oxygen debt

Okay so one last bit. The spec says we should be able to interpret information relating to the effects of lung disease on gas exchange etc. Here we go…

Specific risk factors increase the risk of lung disease (COPD). These include:

• Smoking
• Air pollution - pollutant particles and gases
• Genetic make up - people may be genetically more/less likely to obtain lung disease (explains why some life long smokers never get lung disease)
• Infections - if you frequently get chest infections you’re more likely to have a higher chance of obtaining lung disease
• Occupation - individuals working with harmful chemical/dusts/gases may have an increased risk of obtaining lung disease

Finally, don’t forget that correlation does not mean cause!!

3.3.2: Gas exchange (Limiting water loss)

Features that make a good gas exchange system increase water loss:(

Insects:

Water can leave insects through their spiracles. They have evolved the following adaptations to combat water loss:

• Insects are covered in a rigid outer skeleton of chitin that is covered with a waterproof cuticle
• Small surface area to volume ratio to reduce the area over water which can be lost
• Spiracles can be closed to reduce water loss. This occurs mainly at rest as it conflicts with the insects need for gas exchange

Plants:

Water can leave plant leaves through their stomatal pores. They also have waterproof coverings (a waxy cubicle) but cannot have a small surface area to volume ratio as they need a lot of light for photosynthesis. To help reduce water loss plants have the ability to close their stomatal pores when water loss would be excessive. Xeryphytic plants (xerophytes, plants which live in areas where water is in short supply, e.g deserts) have evolved the ability to limit water loss through transpiration by limiting the rate at which water can be lost through evaporation:

• Rolled leaves protect the (lower) epidermis from the outside, trapping a region of highly saturated still air within the rolled leaf. This still air has the same water potential as the inside of the leaf therefore no water loss occurs. - marram grass
• Stomata in pits of grooves again traps still air resulting in no water loss - pine trees
• Thick cuticle means less water can escape - holly
• Hairy leaves trap still, moist air next to the leaf surface meaning less water is lost by evaporation - a type of heather plant
• By having leaves with a circular cross sectional area (reducing the surface area to volume ratio of the leaves) greatly reduces the rate of water loss. However this reduction in surface area is balanced against the need for a sufficient area for photosynthesis. - pine needles

3.3.2 Gas exchange

Buckle up gas exchange is pretty long…

Gas exchange in larger animals:

As mentioned in 3.3.1, multicellular organisms have a range of adaptations to combat a large surface area to volume ratio. One adaptation I mentioned was a specialised gas exchange surface. Features of this include:

• A large surface area (to increase surface area to volume ratio)
• Thin (to decrease the distance of diffusion meaning materials cross faster)
• Selectively permeable (e.g our lungs are permeable to oxygen and carbon dioxide)
• A means of moving the environmental/external medium (e.g we inhale/exhale to move air to maintain a concentration gradient)
• A transport system of the internal medium (e.g capillaries to move our blood, again to maintain a concentration gradient)

Gas exchange in single celled organisms:

Single celled organisms are very small (duh). As mentioned in 3.3.1, small organisms have a large surface area to volume ratio. It follows that single celled organisms have a very large surface area to volume ratio. They absorb oxygen through their cell-surface membrane by diffusion and release carbon dioxide through their cell-surface membrane by diffusion.

Gas exchange in insects:

Yes, insects are fairly small. Yes, they have a large surface area to volume ratio. However, this increase in surface area conflicts with their conservation of water. Therefore, they have evolved an internal network of tubes known as tracheae and tracheoles (sort of like our bronchi/bronchioles). The trachea are supported by strengthened rings to stop them collapsing (so is our thorax!). Tracheoles are smaller than tracheae and are dead end tubules that extend throughout the body tissue of the insect. Because of this, oxygen is brought right to the respiring tissue, reducing the diffusion distance. 

Yeah, that makes sense, but how does the air actually get in and out of the tubes?

Trachea open at the surface of the insect forming spiracles. Spiracles act sort of like stomata on plant leaves and may be opened/closed by a valve. When spiracles open, gas exchange can occur (but water can also escape!!). Because of this water loss, insects often keep their spiracles closed and only open them when gases need to be exchanged.

Yeah, that makes sense too, but how does the air actually go through the tubes? Well, this occurs in three ways…

• Mass transport - Insects can contract muscles which squeeze the trachea moving air in and out (much like inhalation/exhalation in humans, for example).
• Along a concentration gradient - At the respiring tissue, oxygen is used up so there is little/no oxygen there. This causes gaseous oxygen (in atmospheric air) to diffuse along the trachea and tracheoles. Then quite the opposite occurs, co2 is produced at the respiring tissue which moves out of the insect.
• Diffusion through water - firstly, it is important to point out that diffusion through air is faster than diffusion through water. But, the ends of the tracheoles are filled with water. If anaerobic respiration occurs (e.g during periods of major activity), lactate is produced. Lactate is soluble and lowers the water potential of the cell, meaning the water at the end of the tracheoles moves into the cell by osmosis. This decreases the volume of water at the ends of the tracheoles drawing air further into them meaning the final diffusion pathway is in gaseous phase not liquid phase (which is faster). However, this leads to greater water evaporation.

Gas exchange in fish:

Much like our lungs, fish have gills which increase the surface area of the gas exchange surface. They are made up of gill lamellae which are stacked perpendicular to the gill filaments which increase the surface area of the gills. The flow of water over the gills is in the opposite direction to the flow of blood through the gills. This is known as countercurrent flow and ensures maximum uptake of oxygen from the water. The countercurrent principle ensures that:

• Blood (already partly saturated with oxygen) meets water which is at its maximum oxygen saturation (so diffusion down a concentration gradient, from water to blood, occurs)
• Blood (only a little bit saturated with oxygen) meets water which is at it’s almost minimum oxygen saturation (basically, it’s already lost lots of its oxygen to the other blood). This means that, again, diffusion down a concentration gradient, from water to blood, occurs.

This system maintains the diffusion gradient for the entire width of the gill lamellae, up taking about 80% in total of the oxygen available. Should water flow in the same direction as the blood of fish in gills (a principle known as parallel flow) only 50% of the available oxygen would be absorbed by the blood.

Gas exchange in plant leaves:

I did say that gas exchange was long…..

Okay so the major difference between animal and plant gas exchange is plants also photosynthesise, so also need to take up carbon dioxide (not just oxygen). The volume of gases exchanged by a plant often vary as sometimes the products of photosynthesis can be used as the substrate for respiration and vice versa.

Overall in a leaf there is a short diffusion pathway as leaves are very thin. Much like our alveoli/gills of a fish, air spaces inside the leaf create a very large surface area to volume ratio. Gases just move in and out of the plant by diffusion. Some adaptations of leaves that aid diffusion include:

• Thin leaves to decrease the diffusion distance
• Small pores known as stomata much like insect spiracles - decrease diffusion pathway as no cell is far from a stoma. Each stoma is surrounded by guard cells which open and close the stomatal pore controlling the rate of gas exchange. This is important because it means that plants can balance the conflicting needs of gas exchange and water loss by closing stomatal pores when water loss would be excessive (e.g in warm/very dry conditions).
• Interconnecting air spaces throughout the mesophyll so gases readily come into contact with mesophyll cells
• Large surface area for rapid diffusion

3.3.1 Surface area to volume ratio

Many cells are too far from exchange surfaces to exchange materials by diffusion/active transport alone. To solve this problem, cells of multicellular organisms bathe in tissue fluid (tissue fluid is the environment around the cells). When absorbed, materials are distributed throughout the tissue fluid so cells can absorb them. Example materials include nutrients (e.g fatty acids, amino acids, glucose, minerals, vitamins), gases (respiratory gases, oxygen and carbon dioxide), heat, and urea (and other excretory products).

Along with the metabolic rate of the organism, it’s size also affects the amount of each exchanged material. E.g organisms with a high metabolic rate require a large surface area to volume ratio. This is because lots of the material can be absorbed at once.

Small organisms have a large surface area to volume ratio. Large organisms have a small area to volume ratio (because they have more volume). For effective exchange organisms should have a large surface area to volume ratio as the surface is where the exchange of materials takes place (so small organisms have effective exchange of substances by means such as diffusion and active transport). However, as I said earlier, larger organisms have smaller surface area to volume ratios. This means diffusion/active transport is not sufficient to sustain the organism.

To overcome this, multicellular organisms have developed a range of adaptations including perhaps a flattened shape so no cell is far from the surface, and/or specialised gas exchange surfaces with a large surface area to volume ratio (e.g human alveoli).

Size and surface area: As the size of an organism increases, its surface area to volume ratio decreases. Think of it like this...

Take a small block (say, 1cm by 1cm), its surface area is 6cm² (6 lots of 1x1 cm), its volume is 1cm³ (1x1x1 cm).

Now take a large block (say, 10cm by 10cm),  its surface area is 600cm² (6 lots of 10x10 cm), its volume is 1000cm³ (10 x 10 x 10 cm).

Now look at the ratios...

The smaller block has a SA:VOL of 6:1, whereas the larger block has a smaller SA:VOL of 600:1000 (which cancels down to 0.6:1). This is because as an organisms size increases its surface area to volume ratio decreases.

To investigate this, you could use agar blocks with phenolphthalein. Take cubes of various sizes (e.g 1cm³, 2cm³, 3cm³, 4cm³...) and add them to the same concentration solution of acid. Time how long it takes each to go colourless. This can be used to determine the effect of surface area to volume ratio on the diffusion of an acid.

3.2.4: Cell recognition and the immune system (Viruses (HIV) and ELISA testing)

HIV (human immunodeficiency virus) is a virus which causes AIDS (acquired immune deficiency syndrome) by attacking helper T cells and interfering with their function, reducing the amount of T helper cells in the blood. Without a sufficient number of T helper cells the immune system cannot stimulate enough B cells to produce enough antibodies to combat pathogens/enough cytotoxic T cells to kill infected cells. This means the body is unable to produce enough of an immune response, and this also makes the patient more susceptible to cancers and other infections. It is these infections/diseases that cause death, not the AIDS itself.

HIV belongs to a group of viruses known as retroviruses. The structure:

• Lipid envelope
• Attachment proteins
• Capsid
• Two single strands of RNA
• Enzymes (including reverse transcriptase which catalyses the production of DNA and RNA)

HIV cannot replicate itself as it is a virus. It replicates by...

• HIV enters the bloodstream and circulates around the body
• A protein on HIV binds to a protein on helper T cells
• The capsid fuses with the cell-surface membrane of the T helper cell
• RNA and enzymes enter the T helper cell and the reverse transcriptase converts the viral RNA into DNA (so the host cell can read it).
• This DNA is inserted into the host cells DNA in the nucleus. This DNA creates mRNA which contains instructions for creating new viral proteins and RNA for the new HIVs
• mRNA passes out of the nucleus and it is read and proteins are made
• HIV particles break away from the T helper cell and take a piece of it's cell-surface membrane with it which forms the new lipid envelope.

We also need to know about ELISA testing, not sure where to put it so here it is:

ELISA (enzyme linked immunosorbant assay) uses antibodies to quantify the amount of a protein in a sample. It is useful in both allergen and drug tests. Here is an example of how it works when testing for antigens:

• Apply a sample to the surface of a slide
• Wash the surface to remove any unattached antigens
• Add the antibody that is specific to the antigen, leave for a little bit so the two can bind together
• Wash the surface (again) to remove excess/unbound antibodies
• Add a second antibody that has an enzyme attached to it. This will bind with the first antibody
• Add the colourless substrate of the enzyme
• When the enzyme acts on the substrate, colour is produced
• The amount of antigen present is proportional to the intensity of the colour of the final solution.

Unfortunately, we cannot use antibiotics against viruses. This is because one way in which viruses work is by inhibiting enzymes required for the synthesis of peptide cross-bridges in cell walls. This means that, in bacteria, they can no longer withstand osmotic pressure as their cell wall is very weak and they burst. However, viruses do not have a cell wall. They also do not have any metabolic mechanisms that the antibiotic might be able to disrupt.

3.2.4: Cell recognition and the immune system (Vaccination and immunity)

Immunity is the ability of an organism to resist infection. It can take two forms:

• Active immunity: This is produced by stimulating the production of antibodies by the individuals own immune system by direct contact with the pathogen/antigen. It is generally longer lasting but takes time to develop. There are two kinds of active immunity:
• Artificial active immunity: occurs from immunisation (vaccination). Involves inducing an immune response in an individual without suffering the disease. E.g injecting a dead/inactive form of the pathogen
• Natural active immunity: results from an individual becoming infected with a disease. E.g if I was to obtain a cold my plasma B cells would produce antibodies
• Passive immunity: This is produced by the introduction of antibodies into individuals from an outside source - direct contact with the antigen/pathogen is not required and immunity develops immediately. However, as the body is not producing its own antibodies, the antibodies are not replaced and no memory cells form. This means that immunity is not long lasting. Examples include anti-venom given to victims of snake bites, and antibodies given to baba from mama.

Vaccination involves stimulating an immune response by injecting/swallowing a vaccine. A vaccine contains one or more types of antigen of the appropriate disease. The initial (primary) response is only little but memory cells are produced (this is the important bit!!). These memory cells remain in the blood (humour) and divide, by mitosis, producing plasma B cells and more memory cells if a future infection is detected.

Vaccines must be economically available in sufficient quantities to immunise at least most of the vulnerable population. There must also be few side affects and a means of producing/storing/transporting/administering the vaccine.

Herd immunity

This arrises when a large proportion of the population has been vaccinated. For a pathogen to spread, it must be passed from person to person in close proximity. Since the vast majority of the population are immune, it is very unlikely that a susceptible person comes into contact with another susceptible person - this means that those not vaccinated are still protected from the disease. It is important as not all of the community may be vaccinated. For example, babies are not vaccinated as their immune systems are still developing, individuals may be allergic to an ingredient in the vaccine.

NOTE: it is important to understand that vaccination does not eliminate a disease. For example, as mentioned above, not all individuals can be vaccinated. Also, someone may obtain the disease straight after vaccination when their immunity is not high enough. Also, antigenic variability. 

Vaccine ethics:

Some individuals may have objections to vaccinations for religious/ethical/medical reasons...

• Vaccines have side effects that may cause long term harm
• How should we test vaccines?
• Is it acceptable to involve the use of animals in the production and development of existing/new vaccines?
• It is right that, in the interest of everyone's health, all of the population should be vaccinated (regardless of religious reasons etc)? - basically, should vaccination be compulsory?
• Should expensive vaccination programmes be stopped if the disease is almost eradicated?

3.2.4: Cell recognition and the immune system (B lymphocytes, humoral immunity, and antibodies)

Humoral immunity is called humoral immunity because it involves antibodies and antibodies are soluble in blood and tissue fluid (humour).

There are many different types of B lymphocyte, each produces andifferent antibody in response to a specific antigen. Here's how:

• An antigen (on the surface of a pathogen/foreign cell/toxin, for example) enters the blood/tissue fluid, there will be a B cell that has a complimentary antibody on it's surface
• The antibody attaches to this antigen
• The antigen enters the B cell (by endocytosis)
• The B cell presents the antigien on it's surface (this is also known as 'processing')
• T helper cells (a type of T lymphocyte) binds to the processed antigens and stimulated the B cells to divide by mitosis (clonal selection) to form a clone of identical B cells which all produce the antibody that is specific to the foreign antigen.

Often, some pathogens have many different antigens so many different B cells make clones at the same time. As each clone produces one specific antibody, the antibodies are referred to as monoclonal antibodies. Each clone develops into either:

• Plasma cells: these secrete antibodies (usually) into blood plasma. They survive for only a few days but can make around 2000 antibodies per second (that's quick). These antibodies lead to the destruction of the antigen therefore plasma cells are responsible for the immediate defence of the body against infection. 
• Memory cells: these are responsible for the secondary immune response. They live considerable longer than plasma cells but do not produce antibodies. Instead, they divide rapidly into plasma cells and more memory cells when they encounter the same pathogen once again (e.g a new infection but of the same infection......did that make sense?????not sure lol). The plasma cells they produce in turn produce antibodies to fight the new infection and the new memory cells circulate in the blood and tissue fluid (humour). Because of this, memory cells provide long-term immunity against the original infection. An increased quantity of antibodies is secreted faster the second time round ensuring that the infection sis destroyed before it can cause any/much harm.

NOTE: The production of antibodies and memory cells is known as the primary response.

To summarise, the overall response of B cells:

• Surface antigens of invading pathogen are taken up by a B cell
• The B cell processes the antigens and presents them on its surface
• helper T cells attached to the processed antigens, activating the B cells
• The B cells are stimulated to divide (by mitosis) forming clones of the B cell with the complimentary antibody
• These clones either form plasma or memory cells
• The cloned plasma cels secrete antibodies to attach to and destroy the pathogen
• The cloned memory cells can respond to future infections by dividing rapidly and developing into plasma cells which produce complimentary antibodies (the secondary immune response)

So, what actually are antibodies?

Antibodies are proteins with specific binding sites synthesised by plasma B cells when the body is infected by non-self material. The antibody reacts with a complimentary antigen by binding to it. Each antibody has two specific and identical binding sites. They are made of proteins which leads to a massive variety of antibodies.

They are made up of four polypeptide chains. Two are long (heavy chains) and two are shorter (light chains). As mentioned above, each antibody has a specific binding site that fits very precisely onto a specific antigen forming an antigen-antibody complex. This binding site is different on different antibodies and is therefore known as the variable region (the rest of the antibody is the constant region - this binds to receptors on cells such as B cells).

Antibodies do not directly destroy the antigen, they just prepare it for destruction. If the pathogen is a bacterial cell, the antigen can prepare it in one of two ways:

• Cause agglutination (clumps of the bacterial cell form, making it easier for the phagocytes to locate them as they are less spread out)
• Act as markers that stimulate phagocytes to engulf the bacterial cell to which they are attached (phagocytosis)

It is of medical value if we can produce a single type of antibody outside of the cell, these are known as monoclonal antibodies. Some uses of monoclonal antibodies are:

• Direct/indirect monoclonal antibody therapy.
• Monoclonal antibodies are produced that are specific to cancer cells (for example)
• These antibodies are administered to a patient and attach themselves to the receptors on the cancer cells
• They block the chemical signals that stimulate the uncontrolled growth of the cancer cells.
• The advantages of this is that, since antibodies are highly specific and not toxic, they lead to fewer side effects than other forms of therapy (e.g chemo/radiotherapy)
• Indirect monoclonal antibody therapy involves attaching a cytotoxic/radioactive drug to the antibody, therefore the cell that the antibody attaches to dies
• They can be used in small doses which is cheaper and less invasive and reduces the side effects of other drugs that may be used alternatively
• Medical diagnosis
• They are used for the diagnosis of hepatitis/chlamydia/influenza infections as they produce a much more rapid result than conventional methods of diagnosis
• One example is prostate cancer: men with prostate cancer often produce higher numbers of PSA (prostate specific antigen). By using a monoclonal antibody that reacts with this antigen is is possible to obtain a measure of the amount of PSA in a mans blood. Whilst this does not diagnose the disease it gives a good indication/early warning that the cancer may be present
• Pregnancy testing
• Placenta produces a hormone known as hCG (human chorionic gonadatrophin). This is present in mamas urine
• Monoclonal antibodies linked to coloured particles are present on home pregnancy tests
• If hCG is present it binds to these antibodies and the hCG-antibody complex moves along the strip creating a coloured line

Monoclonal antibody ethical issues:

• Monoclonal antibody production involves inducing mice with cancer to create tumour cells
• There have been some deaths associated with the use of monoclonal antibodies and multiple sclerosis treatment
• in March 2006 six healthy volunteers trialed a new monoclonal antibody and within minutes suffered multiple organ failures, although all survived.
• Monoclonal antibodies have been used successfully to treat a number of diseases

3.2.4 Cell recognition and the immune system (T lymphocytes and cell-mediated immunity)

An antigen is any part of an organism/substance that is recognised as non-self (foreign) by the immune system and stimulates an immune response. The presence of an antigen stimulates the production of antibodies.

As mentioned in 3.2.4 Defence mechanisms, immune responses such as phagocytosis are non-specific. Specific responses are slower but can provide longer lasting immunity. The type of response (humoral or cell-mediated) displayed depends on the white blood cell present. There are two types of lymphocyte:

• B lymphocytes (mature in the bone marrow, think B for Bone). These are associated with humoral immunity (immunity involving antibodies present in body fluids or humour such as blood plasma)
• T lymphocytes (mature in the thymus gland, thing T for Thymus). These are associated with cell-mediated immunity/cellular response (immunity involving body cells).

Cell mediated immunity/cellular response:

Invader cells have different antigens on their surface to antigens on self-cells. T lymphocytes can distinguish invader cells from normal cells because:

• Phagocytes that have engulfed and hydrolysed a pathogen (phagocytosis) present some of a pathogen's antigens on their own cell surface membrane
• Body cells invaded by a virus present viral antigens on their own cell surface membranes
• Transplanted cells from individuals of the same species have different antigens on their cell-surface membrane
• Cancer cells present antigens on their cell surface membrane

Cells that display foreign antigens on their surface are known as antigen-presenting cells as they can present antigens of other cells on their own cell surface membrane.

T lymphocytes differ from B lymphocytes as T lymphocytes will ONLY respond to antigens that are present on a body cell (rather than within body fluids). The receptors on T each T cell responds to a single antigen. It follows that there is a vast number of T lymphocytes, each responding to one antigen. The 'method' of cell-mediated immunity/cellular response is:

• Pathogens are taken in by phagocytes
• The phagocyte places antigens from the pathogen on its cell-surface membrane
• Receptors on a specific helper T cell fit onto these antigens
• This attachment activated the T cells to divide rapidly by mitosis and form a clone of genetically identical cells (clonal selection)
• These cloned T cells can either:
• Develop into memory cells that enable a rapid secondary response (for if the pathogen invades the body once again)
• Stimulate phagocytes to engulf pathogens by phagocytosis
• Stimulate B cells to divide and secrete their antibody
• Activate cytotoxic T cells. Cytotoxic T cells kill abnormal body cells/infected body cells by producing the protein perforin that makes holes in the cell-surface membrane meaning the membrane becomes freely permeable to all substances and the cell dies.

NOTE: The action of T cells is most effective against viruses as viruses replicate inside other cells.

Okay so i'm not too sure where to slot this next bit in but it's in the spec so i'll just put it here:

The effect of antigen variability on disease and disease prevention. Antigenic variability means that the antigens on the surface of the pathogen are constantly changing so, every time you're infected, you're immune system will not have the memory cells with complimentary antibodies, so the above process will have to start all over again. This means there will not be a rapid secondary response to the pathogen ( as it is technically a different pathogen). Therefore, even if you were vaccinated against the 'old' pathogen, since it's antigens have changed you're vaccine will not prevent you against infection. The common cold is a good example here, everyone gets infected pretty frequently (well, I do anyway). This is because each time you get infected with a slightly different pathogen, so you don't have the built up immune responses to immediately fight against it.