Cells 2.3-2.4 Flashcards
1
Q
Phospholipids
A
Cell surface membrane
The hydrophilic heads of both phospholipid layers point to the outside of the cell surface membrane attracted by water on both sides
The hydrophobic tails of both layers point into the membrane, repelled by water on both sides
Lipid-soluble material moves through the membrane via the phospholipid portion.
2
Q
The functions of phospholipids in the membrane are to:
A
Allow lipid-soluble substances to enter and leave the cell
Prevent water-soluble substances entering and leaving the cell
Make the membrane flexible and self-sealing
3
Q
Proteins- membrane
A
Interspersed throughout the cell surface membrane
Embedded in the phospholipid bilayer in two ways
4
Q
2 ways proteins are embedded into the phospholipid bilayer
A
extrinsic- Some proteins occur in the surface of the bilayer and never extend completely across it. They act either to give mechanical support to the membrane or, in conjunction with glycolipids, as cell receptors for molecules such as hormones
intrinsic- Other proteins completely span the phospholipid bilayer from one side to the other. Some are protein channels others are carrier proteins
5
Q
Protein channels
A
Form water filled hydrophilic channels across the membrane. They allow specific water soluble ions to pass through. The channels are selective, each opening in the presence of a specific ion. If the particular ion is not present, the channel remains closed. In this way, there is control over the entry and exit of ions. The ions bind with the protein causing it to change shape in a way that closes it to one side of the membrane and opens it to the other side
6
Q
Carrier proteins
A
And alternative form of facilitated diffusion involves carrier proteins that span the plasma membrane. When molecules such as glucose that is specific to the protein is present, it binds with the protein. This causes it to change shape in such a way that the molecule is released to the inside of the membrane. No external energy is needed for this. The molecules move from a region where they are highly concentrated to one of lower concentration, using only the kinetic energy of the molecules themselves
7
Q
Functions of proteins in the membrane
A
Provide structural support
Act as channels transporting water soluble substances across the membrane
Allow active transport across the membrane through carrier proteins
Form cell surface receptors for identifying cells
Help cells adhere together
Act as receptors, for example for hormones
8
Q
Cholesterol
A
Occur within that phospholipid bilayer of the cell surface membrane
Adds strength to the membranes
Cholesterol molecules are very hydrophobic and therefore play a role in preventing loss of water and dissolved ions from the cell
They pull together the fatty acid tails of the phospholipid molecules, limiting their movement and that of other molecules but without making the membrane as a whole too rigid
9
Q
Functions of cholesterol in the membrane
A
Reduces lateral movement of other molecules including phospholipids
Make the membrane less fluid at high temps
Prevent leakage of water and dissolved ions from the cell
10
Q
Glycolipids
A
Made up of a carbohydrate covalently bonded with a lipid
The carbohydrate portion extends from the PL bilayer into the watery environment outside the cell where it acts as a cell surface receptors for specific chemicals, e.g. the human ABO blood system operates as a result of glycolipids on the cell surface membrane
11
Q
Functions of glycolipids in the membrane
A
Act as a recognition sites
Help maintain the stability of the membrane
Help cells to attach to one another and form tissues
12
Q
Glycoproteins
A
Carbohydrate chains are attached to many extrinsic proteins on the outer surface of the cell membrane. These glycoproteins also act as cell-surface receptors, more specifically for hormones and neurotransmitters
13
Q
Functions of glycoproteins in the membrane
A
Act as recognition sites
Help cells to attach to one another and so form tissues
Allows cells to recognise one another, for example lymphocytes can recognise an organism’s own cells
14
Q
Permeability of the cell surface membrane
A
It controls the movement of substances into and out of the cell. In general most molecules do not freely diffuse across it because many are:
Not soluble in lipids and therefore cannot pass through the phospholipid layer
Too large to pass through the channels in the membrane
Of the same charge as the charge on the protein channels and so, even if they are small enough to pass through, they are repelled
Electrically charged and therefore have difficulty passing through the nonpolar hydrophobic tails in the phospholipid bilayer
15
Q
Fluid-Mosaic model of the cell surface membrane
A
The way in which all the various molecules are combined into the structure of the cell surface membrane. This arrangement is known as the fluid Mosaic model for the following reasons:
Fluid – because the individual phospholipid molecules can move relative to one another. This gives the membrane a flexible structure that is constantly changing shape
Mosaic – because the proteins that are embedded in the phospholipid bilayer vary in size, shape and pattern in the same way as the stones or tiles of a mosaic
16
Q
Explanation of simple diffusion
A
The net movement of molecules or ions from a region where they are more highly concentrated to one where the concentration is lower until evenly distributed
17
Q
Facilitated diffusion
A
A passive process
It relies only on the inbuilt motion (kinetic energy) of the diffusing molecules. There is no external input of ATP from respiration. Like diffusion, it occurs down a concentration gradient, but it differs in that it occurs at specific points on the plasma membrane where there are special protein molecules. Two types of protein are involved – protein channels and carrier proteins. Each has a different mechanism
18
Q
Osmosis
A
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 selectively permeable membrane
19
Q
Solute
A
Any substance that is dissolved in a solvent, for example water. The solute and the solvent together form a solution
20
Q
Water potential
A
Represented by the Greek letter psi and is measured in units of pressure, usually kilopascals. Water potential is the pressure created by water molecules. Under standard conditions of temperature and pressure, pure water is said to have a water potential of zero
It follows that:
The addition of solute to pure water will lower its water potential
The water potential of the solution must always be less than zero
The more solute that is added the lower its water potential
Water will move by osmosis from a region of higher water potential to one of lower water potential
21
Q
A way of finding the water potential of cells or tissues
A
Place them in a series of solutions of different water potentials. Where there is no net gain or loss of water from the cells or tissues, the water potential inside the cells and tissues must be the same as that of the external solution
22
Q
Explanation of osmosis
A
One of the solutions has a low concentration of solute molecules while the other solution has a high concentration.
Both the solute and the water molecules are in random motion due to the kinetic energy
The selectively permeable plasma membrane only allows water molecules across it and not solute molecules
Water molecules diffuse from the higher water potential to the lower potential, this is down the water potential gradient
At the point where the water potential either side of the plasma membrane are equal, a dynamic equilibrium is established and there is no net movement of water
23
Q
Understanding water potential
A
The highest value of water potential, that of pure water, is zero, and so all other values are negative. The more negative the value, the lower the water potential
24
Q
Osmosis and animal cells
A
Animal cells such as red blood cells contain a variety of solute is dissolved in the water in their cytoplasm. If a red blood cell is placed in pure water it will absorb water by osmosis because it has a lower water potential. Cell surface membranes are very thin and although they are flexible they cannot stretch to any great extent
The cell-surface membrane will therefore break, bursting the cell and releasing its contents. To prevent this happening animal cells normally live in a liquid which has the same water potential as the cells. In this example the liquid is the blood plasma. This and red blood cells have the same water potential. If a red blood cell was placed in a solution with a water potential lower than its own, water leaves by osmosis and the cell shrinks and becomes shrivelled
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Active transport
The movement of molecules or ions into or out of a cell from a region of low concentration to a region of higher concentration using ATP and carrier proteins
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In active transport ATP is used to:
Directly move molecules
Individually move molecules using a concentration gradient which has already been set up by active transport. This is known as co-transport
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How does active transport differ from passive forms of transport
Metabolic energy in the form of ATP is needed
Substances are moved against a conc gradient, from a lower to a higher conc
Carrier protein molecules which act as pumps are involved
The process is very selective, with specific substances being transported
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Direct active transport of a single molecule or ion description
The carrier proteins span the plasma membrane and bind to the molecule or ion to be transported on one side of it
The molecule or ion binds to receptor sites on the carrier protein
On the inside of the cell/organelle, ATP binds to the protein, causing it to split into ADP and a phosphate molecule. As a result, the protein molecule changes shape and opens to the opposite side of the membrane
The molecule or ion is then released to the other side of the membrane
The phosphate molecule is released from the protein which causes the protein to revert to its original shape, ready for the process to be repeated. The phosphate molecule then re-combines with the ADP to form ATP during respiration
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Difference between active transport and facilitated diffusion
Both use carrier proteins but facilitated diffusion occurs down a concentration gradient, while active transport occurs against a concentration gradient. This means that facilitated diffusion does not require metabolic energy, while active transport does. The metabolic energy is provided in the form of ATP
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Sodium potassium pump
Sodium ions are actively removed from the cell/organelle while potassium ions are actively taken from the surroundings. This process is essential to a number of important processes in the organism, including the creation of a nerve impulse
Molecules bind to the carrier protein and ATP attaches to the membrane protein on the inside of the cells/organelle
Binding of phosphate ions to protein causes the protein to change shape so that access for the molecules is open to the inside of the membrane but close to the outside
31
How is the rate of transport across membranes and into cells affected by increasing the rate of movement across membranes?
The epithelial cells lining the ileum possesses microvilli. These are fingerlike projections on the cell-surface membrane. The microvilli provide more surface area for the insertion of carrier proteins through which diffusion, facilitated diffusion and active transport can take place.
Another mechanism to increase transport across membranes is to increase the number of protein channels and carrier proteins in any given area of the membrane
32
The role of diffusion in absorption
As carbohydrates and proteins are being digested continuously, there is normally a greater concentration of glucose and amino acids within the ileum than in the blood. There is therefore a concentration gradient down which glucose moves by facilitated diffusion from inside the ileum into the blood.
Given that the blood is constantly being circulated by the heart, the glucose absorbed into it is continuously being removed by the cells as they use it up during respiration. This helps to maintain the concentration gradient between the inside of the ileum and the blood. This means the rate of movement by facilitated diffusion across epithelial cell surface membranes is increased
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Role of active transport in absorption
Diffusion only results in the concentrations either side of the intestinal epithelium becoming equal. This means that not all the available glucose and amino acids can be absorbed in this way and some may pass out of the body. The reason why this doesn’t happen is because glucose and amino acids are also being transported by active transport. This means that all the glucose and amino acid should be absorbed into the blood
The actual mechanism by which they are absorbed from the small intestine is an example of co-transport. This term is used because either glucose or amino acids are drawn into the cells along which sodium ions that have been actively transported out by the sodium potassium pump.
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Co-transport of glucose
1. sodium ions are actively transported out of the epithelial cells, by the sodium potassium pump, into the blood. This takes place in one type of protein – carrier molecule found in the cell surface membrane of epithelial cells
2. This maintains a much higher concentration of sodium ions in the lumen of the intestine than inside the epithelial cells
3. Sodium ions diffuse into the epithelial cells down this concentration gradient through a different type of protein carrier (co-transport protein) in the cell surface membrane. As the sodium ions diffuse in through the second carrier protein, they carry either amino acid molecules or glucose molecules into the cell with them
4. The glucose/amino acids pass into the blood plasma by facilitated diffusion and using another type of carrier
Both sodium ions and glucose/amino acid molecules move into the cell, but while the sodium ions move down their concentration gradient, glucose molecules move against their concentration gradient. It is the sodium ion concentration gradient, rather than ATP directly, that powers the movement of glucose and amino acids into the cells. This makes it an indirect rather than a direct form of active transport
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Infection
An interaction between the pathogen and the body’s various defense mechanisms
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Immunity
If the bodies defence mechanisms overwhelm the pathogen the bodies defences seem to be better prepared for a second infection from the same pathogen and can kill it before it can cause any harm
Immunity is the main reason why some people are unaffected by certain pathogens
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Defence mechanisms
The body has a range of defences to protect itself from pathogens. Some are general and immediate defences like the skin forming a barrier to the entry of pathogens and phagocytosis. Others are more specific, less rapid but long-lasting. These responses involve a type of white blood cell called lymphocytes and take two forms:
– cell mediated responses involving T lymphocytes
– humoral responses involving B lymphocytes
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The two types of defence mechanisms
Non-specific
| Specific
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Non-specific defence mechanisms
Response is immediate and the same for all pathogens
Physical barrier e.g. skin
Phagocytosis
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Specific defence mechanism
Response is slow and specific to each pathogen
Cell mediated response – T lymphocytes
Humoral response – B lymphocytes
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Recognising your own cells
To defend the body from invasion by foreign material, lymphocytes must be able to distinguish the body’s own cells and molecules (self) from those that are foreign (non-self)
Each type of cell, self or non-self, has specific molecules on its surface that identify it.
While these molecules can be of a variety of types, it is the proteins that are the most important. This is because proteins have enormous variety and a highly specific tertiary structure. It is this variety of specific 3-D structure that distinguishes one cell from another.
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protein molecules allow the immune system to identify:
Pathogens for example the human immunodeficiency virus
Nonself material such as cells from other organisms of the same species
Toxins including those produced by certain pathogens like the bacteria that causes cholera
Abnormal body cells such as cancer cells
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Tissue or organ transplants disadvantage
Immune system recognises these as nonself even though they have come from individuals of the same species. It therefore attempts to destroy the transplant.
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What is done to minimise the effects of tissue rejection
Donor tissues for transplants are normally matched as closely as possible to those of the recipient. The best matches often come from relatives that are genetically close.
In addition, immunosuppressant drugs are often administered to reduce the level of immune response that still occurs
45
Clonal selection brief summary
Lymphocytes aren’t produced in response to an infection, but they already exist- all 10 million different types. Given that there’s so many types, there is a high probability that when a pathogen gets into the body, one of these lymphocytes will have a protein on its surface that’s complementary to to one of the proteins of the pathogen. So the lymphocyte will ‘recognise’ the pathogen. There are very few of each type of lymphocyte.
When an infection occurs, the one type already present that has the complementary proteins to those of the pathogen is stimulated to divide to build up its numbers to a level where it can be effective in destroying it
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How lymphocytes recognise cells belonging to the body
Around 10 million different lymphocytes present at any time, each capable of recognising a different chemical shape
In the foetus, these lymphocytes are constantly colliding with other cells
Infection in the foetus is rare because it is protected from the outside world by the mother and the placenta
Lymphocytes will therefore collide almost exclusively with the body’s own material (self)
Some of the lymphocytes will have receptors that exactly fit those of the body’s own cells
These lymphocytes either die or are suppressed
The only remaining lymphocytes are those that might fit foreign material (non self), and therefore only respond to foreign material
In adults, lymphocytes produced in the bone marrow initially only encounter self antigens
Any lymphocytes that show an immune response to these self-antigens undergo programmed cell death before they can differentiate into mature lymphocytes
No clones of these anti-self lymphocytes will appear in the blood, leaving only those that might respond to non-self antigens
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Body’s first line of defence
To form a physical or chemical barrier to entry
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Body’s second line of defence
White blood cells
| There are two types of white blood cell:phagocytes and lymphocytes
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Phagocytes versus lymphocytes
Phagocytes ingest and destroy the pathogen by a process called phagocytosis before it can cause harm
Lymphocytes are involved in immune responses
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Body’s third line of defence
Phagocytosis
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Phagocytosis
Large particles such as some types of bacteria can be engulfed by cells in the vesicles formed from the cell-surface membrane. This process is called phagocytosis. In the blood the types of white blood cells that carry out phagocytosis are known as phagocytes. They provide an important defence against the pathogens that manage to enter the body. Some phagocytes travel in the blood but can move out of blood vessels into other tissues.
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Phagocytosis steps
Chemical products of pathogens or dead, damaged and abnormal cells act as attractants, causing phagocytes to move towards the pathogen (e.g. a bacterium)
Phagocytes have several receptors on their cell surface membrane that recognise, and attach to, chemicals on the surface of the pathogen
The engulf the pathogen to form a vesicle known as a phagosome
Lysosomes move towards the vesicle and infuse with it
Enzymes called lysozymes are present within the lysosome. These lysozymes destroy ingested bacteria by hydrolysis of their cell walls. The process is the same as that for the digestion of food in the intestines, namely the hydrolysis of larger, insoluble molecules into smaller, soluble ones
The soluble products from the breakdown of the pathogen are absorbed into the cytoplasm of the phagocyte
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Antigens
Any part of an organism or substance that is recognised as non-self (foreign) by the immune system and stimulates an immune response. Antigens are usually proteins that are part of the cell surface membranes or cell walls of invading cells, such as microorganisms, or abnormal body cells, such as cancer cells. The presence of an antigen triggers the production of an antibody as part of the body’s defence system
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Lymphocytes
Immune responses such as phagocytosis are non-specific and occur whatever the infection. The body also has specific responses that react to specific antigens. These are slower in action at first but they can provide long-term immunity. This specific immune response depends on the type of white blood cells called lymphocytes. Lymphocytes are produced by stem cells in the bone marrow. There are two types of lymphocytes, each with its own role in the immune response: B lymphocytes and T lymphocytes
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B lymphocytes
They mature in the bone marrow. They are associated with humoural immunity, that is, immunity involving antibodies that are present in body fluids, or ‘humour’ such as blood plasma.
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T lymphocytes
They mature in the thymus gland. They’re associated with cell mediated immunity, that is immunity involving body cells
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Cell mediated immunity
Lymphocytes respond to an organism’s own cells that have been infected by non self material from a different species e.g. a virus
They also respond to cells from other individuals of the same species because these are genetically different. These therefore have different antigens on their cell surface membrane from the antigens in the organism’s own cells
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T lymphocytes can distinguish these invader cells from normal cells because:
Phagocytes that have engulfed and hydrolysed a pathogen present some of a pathogen’s antigens on their own cell surface membrane
Body cells invaded by a virus present some of the viral antigens on their own cell surface membrane
Transplanted cells from individuals of the same species have different antigens on their cell surface membrane
Cancer cells are different from normal body cells and present antigens on their cell surface membranes
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Antigen presenting cells
Cells that display foreign antigens on their surface
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Summary of the stages in the response of T lymphocytes to infection by a pathogen
Pathogens invade body cells or 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 exactly into these antigens
This attachment activates the T cell to divide rapidly by mitosis and form a clone of genetically identical cells
The clones T cells:
-develop into memory cells that enable a rapid response to future infections by the same pathogen
- stimulate phagocytes to engulf pathogens by phagocytosis
- stimulate B cells to divide and secrete their antibody
- activate cytotoxic T cells
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How cytotoxic T cells kill infected cells
Cytotoxic T cells kill abnormal cells and body cells that are infected by pathogens, by producing a protein called perforin that makes holes in the cell surface membrane
These holes mean the cell membrane becomes freely permeable to all substances and the cell dies as a result
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Humoral immunity- clonal selection
Involves antibodies- antibodies are soluble in the blood and tissue fluid of the body
Many different types of B cell, possibly as many as 10million, and each B cell starts to produce a specific antibody that responds to one specific antigen
When an antigen, e.g. a protein on the surface of a pathogen, foreign cell toxin, damaged or abnormal cell, enters the blood or tissue fluid, there will be one B cell that has an antibody on its surface whose shape exactly fits the antigen, that is, they are complementary.
The antibody therefore attaches to this complementary antigen. The antigen enters the B cell by endocytosis and gets presented on its surface. T helper cells bind to these processed antigens and stimulate this B cell to divide by mitosis to form a clone of identical B cells, all of which produce the antibody that is specific to the foreign antigen
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In each clone from clonal selection, the cells produces develop into one of two types of cells:
Plasma cells
| Memory cells
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Plasma cells
Secrete antibodies usually into the blood plasma
These cells survive for only a few days, but each can make around 2000 antibodies every second during its brief lifespan
These antibodies lead to the destruction of the antigen. The plasma cells are therefore responsible for the immediate Defence of the body against infection
The production of antibodies and memory cells is known as the primary immune response
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Memory cells
Responsible for the secondary immune response. Memory cells live considerably longer than plasma cells, often for decades. These cells do not produce antibodies directly, but circulate in the blood and tissue fluid. When they encounter the same antigen at a later date, they divide rapidly and develop into plasma cells and more memory cells.
The plasma cells produce the antibodies needed to destroy the pathogen, while the new memory cells circulate in readiness for any future infection. In this way, memory cells provide long-term immunity against the original infection.
An increased quantity of antibodies are secreted at a faster rate than in the primary immune response. It ensures that a new infection is destroyed before it can cause any harm – and individuals are often totally unaware that they have even been affected.
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Summary of role of B cells in humoral immunity
The surface antigens of an invading pathogen are taken up by a B cell
The B-cell produces the antigens and presents them on its surface
Helper T cells attach to the processed antigens on the B cell thereby activating the B cell
The B-cell is now activated to divide by mitosis to give a clone of plasma cells
The cloned plasma cells produce and secrete the specific antibody that exactly fits the antigen on the pathogen’s surface
The antibody attaches to antigens on the pathogen and destroys them
Some B cells develop into memory cells. These can respond to future infections by the same pathogen by dividing rapidly and developing into plasma cells that produce antibodies. This is the secondary immune response
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Antibodies
Proteins with specific binding sites synthesised by B cells. When the body is infected by nonself material, a B cell produces a specific antibody. The specific antibody reacts with an antigen on the surface of the nonself material by binding to them.
Each antibody has two identical binding sites. The Antibody binding sites are complimentary to a specific antigen. The massive variety of antibodies is possible because they’re made of proteins – molecules that occur in an almost infinite number of forms
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Antibody structure
Made up of four polypeptide chains. The chains of one pair are long and are called heavy chains, while the chains of the other pair are shorter and are known as light chains. Each antibody has a specific binding site that fits very precisely onto a specific antigen to form what is known as an antigen-antibody complex.
The binding site is different on different antibodies and is therefore called the variable region. Each binding site consists of a sequence of amino acids that form a specific 3-D shape that binds directly to a specific antigen.
The rest of the antibody is known as the constant region. This binds to receptors on cells such as B cells.
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How the antibody leads to the destruction of the antigen
Antibodies don’t destroy antigens directly but rather prepare the antigen for destruction. Different antibodies lead to the destruction of an antigen in a range of ways. E.g. when the antigen is a bacterial cell – antibodies assist in its destruction in two ways:
- They cause agglutination of the bacterial cells. In this way cancer bacterial cells are formed, making it easier for the phagocytes to locate them as they are less spreadout within the body
- They then serve as markers that stimulate phagocytes to engulf the bacterial cells to which they are attached
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Monoclonal antibodies
We have seen that a bacterium or other microorganism entering the body is likely to have many hundreds of different antigens on its surface. Each antigen will induce a different B-cell to multiply and form a clone of itself.
Each of these clones will produce a different antibody. It is of considerable medical value to be able to produce antibodies outside the body. It is even better if a single type of antibody can be isolated and cloned. Such antibodies are known as monoclonal antibodies
Monoclonal antibodies have a number of useful functions in science and medicine
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Targeting medication to specific cell types by attaching a therapeutic drug to an antibody
As an antibody is very specific to particular antigen, monoclonal antibodies can be used to target specific substances and specific cells. One type of cell they can target is cancer cells. Monoclonal antibodies can be used to treat cancer in a number of ways. By far the most successful so far is direct Monoclonal antibody therapy
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Direct monoclonal antibody therapy
Monoclonal antibodies are produced that are specific to antigens on cancer cells
These antibodies are given to a patient and attach themselves to the receptors on the cancer cells
They Attach to the surface of the cancer cells and block the chemical signals that stimulate the uncontrolled growth
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Indirect monoclonal antibody therapy
Involves attaching a radioactive or cytotoxic drug (a drug that kills cells) to the monoclonal antibody. When the antibody attaches to the cancer cells, it kills them
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Monoclonal antibodies in medical diagnosis
Monoclonal antibodies are an invaluable tool in diagnosing disease with over 100 different diagnostic products based on them. They are used for the diagnosis of influenza, hepatitis and chlamydia infections where they produce a much more rapid results than conventional methods of diagnosis.
They are important in diagnosing certain cancers. For example, men with prostate cancer often produce more of a protein called prostate specific antigen leading to unusually high levels of it in the blood. By using a monoclonal antibody that interacts with this antigen, it is possible to obtain a measure of the level of PSA in a sample of blood. While a higher than normal level of PSA is not itself diagnostic of the disease, it gives an early warning of its possibility and the need for further tests.
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Monoclonal antibodies in pregnancy testing
Pregnancy kits rely on the fact that the placenta produces a hormone called human chorionic gonadotropin (hCG) and that this is found in the mother’s urine.
Monoclonal antibodies present on the test strip of a home pregnancy testing kit are linked to coloured particles. If hCG is present in the urine it binds to these antibodies. The hCG-antibody-colour complex moves along the strip until it is trapped by a different type of antibody creating a coloured line
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Monoclonal antibodies ethical issues
– Production of monoclonal antibodies involves the use of mice. These mice are used to produce both antibodies and tumour cells. The production of tumour cells involves deliberately inducing cancer in mice. Despite the specific guidelines drawn up to minimise any suffering, some people still have reservations about using animals in this way.
- monoclonal antibodies have been used successfully to treat a number of diseases, including cancer and diabetes, saving many lives. There have also been some deaths associated with their use in the treatment of multiple Sclerosis. It is important that patients have full knowledge of the risks and benefits of these drugs before giving permission for them to be used (= informed consent).
- testing for the safety of new drugs presents certain dangers. In March 2006, six healthy volunteers took part in the trial of the new monoclonal antibody in London. Within minutes they suffered multiple organ failure, probably as a result of T cells over producing chemicals that stimulate and immune response or attacking the body tissues. All the volunteers survived, but it raises issues about the conduct of drug trials
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Immunity
The ability of an organism to resist infection.
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Two forms of immunity
Passive immunity
| Active immunity
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Passive immunity
Is produced by the introduction of antibodies into individuals from an outside source. No direct contact with the pathogen or is antigen is necessary to induce immunity. Immunity is acquired immediately.
As the antibodies are not being produced by the individuals themselves, the antibodies are not replaced when there are broken down, no memory cells are formed and there is no lasting immunity. Examples of passive immunity include antivenom given to the victims of snakebites and the immunity acquired by the fetus when antibodies pass across the placenta from the mother
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Active immunity
Is produced by stimulating the production of antibodies by the individuals’ own immune system. Direct contact with the pathogen or its antigen is necessary. Immunity takes time to develop
Generally long lasting and has two types:
-natural active immunity
- artificial active immunity
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Natural active immunity
Results from an individual becoming infected with a disease under normal circumstances
The body produces its own antibodies and may continue to do so for many years
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Artificial active immunity
Forms the basis of vaccination (immunisation)
| It involves inducing an immune response in an individual, without them suffering the symptoms of the disease
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Vaccination
The introduction of the appropriate disease antigens into the body, either by injection or by mouth
The intention is to stimulate an immune response against a particular disease
The material introduced is called vaccine and, in whatever form, it contains one or more types of antigen from the pathogen
These antigens stimulate the immune response. The response is slight because only a small amount of antigen has been introduced, however the crucial factor is that memory cells are produced. These remain in the blood and allow a greater, and more immediate, response to a future infection with the pathogen
The result is that there is a more rapid production of antibodies and the new infection is rapidly overcome before it can cause any harm and with few, if any, symptoms
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Features of a successful vaccination programme
– A suitable vaccine must be economically available in sufficient quantities to immunise most of the vulnerable population
- there might be few side-effects, if any, from the vaccination. unpleasant side-effects may discourage individuals in the population from being vaccinated.
- means of producing, storing and transporting the vaccine must be available. This usually involves technologically advanced equipment, hygienic conditions and refrigerated transport.
- there must be means of administering the vaccine properly at the appropriate time. This involves training staff with appropriate skills at different centres throughout the population.
- It must be possible to vaccinate the vast majority of the vulnerable population to produce herd immunity.
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Herd immunity
Herd immunity arises when a sufficiently large proportion of the population has been vaccinated to make it difficult for a pathogen to spread within that population.
The concept is based on the idea that pathogens are passed from individual to individual when in close contact. Where the vast majority of the population is immune, it is highly improbable that a susceptible individual will come in contact with an infected person. In this way those individuals who are not immune to the disease are nevertheless protected
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Why is herd immunity important
It is never possible to vaccinate everyone in a large population. For example, babies and very young children are not vaccinated because their immune system is not yet fully functional. It could also be dangerous to vaccinate those who are ill or have compromised immune systems. The percentage of the population that must be vaccinated in order to achieve herd immunity is different for each disease. To achieve herd immunity, vaccination is best carried out at one time. This means that for a certain period there are very few individuals in a population with the disease and the transmission of the pathogen is interrupted.
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Why vaccinations may not eliminate a disease
-Vaccination fails to induce immunity in certain individuals, for example people with defective immune systems
– individuals may develop the disease immediately after vaccination but before their immunity levels are high enough to prevent it. These individuals may harbour the pathogen and reinfect others.
-The pathogen may mutate frequently, so that its antigens change suddenly rather than gradually. This means that vaccines suddenly become ineffective because the new antigens on the pathogen are no longer recognised by the immune system. As a result the immune system does not produce antibodies to destroy the pathogen. This antigenic variability happens with the influenza virus, which changes its antigens frequently. Immunity is therefore short lived and individuals may develop repeated bouts of influenza during the lifetime.
- there may be so many varieties of a particular pathogen that it is almost impossible to develop a vaccine that is affective against them all. For example, there are over 100 varieties of the common cold virus and new ones are constantly evolving.
- certain pathogens hide from the body’s immune systems, either concealing themselves inside cells or by living in places out of reach, such as within the intestines, for example, cholera pathogen
- individuals may have objections to vaccination for religious ethical or medical reasons. For example, unfounded concerns over the measles, mumps and rubella triple vaccine has led a number of parents to opt for separate vaccinations for their children or to avoid vaccination altogether
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Ethics of using vaccines
– The production of existing vaccines, and the development of new ones, often involves the use of animals. How acceptable is this?
– Vaccines have side-effects that may sometimes cause long-term harm. How can the risk of side-effects be balanced against the risk of developing a disease that causes even greater harm?
-on whom should vaccines be tested? How should such trials be carried out? To what extent should individuals be asked to accept risk in the interest of the public health?
-is it acceptable to trial a new vaccine with unknown health risks only in a country where the targeted disease is common, on the basis that the population there has most to gain if it proves successful?
- to be fully effective the majority, and preferably all, of the population should be vaccinated. Is it right, in the interests of everyone’s health that the vaccination should be compulsory? If so, should this be at any time, or just when there is a potential epidermic? Can people opt out? If so, on what grounds: religious belief, medical circumstances, personal belief?
- should expensive vaccination programmes continue when a disease is almost eradicated, even though this might mean less money for the treatment of other diseases?
- how can any individual health risks from vaccination be balanced against the advantage of controlling disease and the benefit of the population at large?
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Structure of HIV
On outside – lipid envelope, embedded with peg-like attachment protein
Inside envelope – protein layer (capsid) encloses two single strands of RNA and some enzymes.
One enzyme – reverse transcriptase; catalyses production of DNA from RNA
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Replication of HIV
Being a virus, HIV cannot replicate itself
It uses its genetic material to instruct host cell’s biochemical mechanisms
– HIV enters bloodstream and circulates around body
– protein only HIV binds to protein (CD4); occurs on a number of different cells
- HIV attaches to helper T cells and protein capsid fuses with cell-surface membrane. RNA and enzymes of HIV enter T-helper cell
- HIV reverse transcriptase converts virus’ RNA into DNA
- newly made DNA is moved into T-helper cells’ nucleus; inserted into cells’ DNA
- HIV DNA in the nucleus creates mRNA; contains instructions for making new viral proteins and RNA to go into new HIV
- mRNA passes out of nucleus through nuclear pore and uses cells’ protein synthesis to make HIV particles
- HIV particles break away from T-helper cell; forms lipid envelope
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How HIV causes symptoms of AIDS?
HIV attacks helper T cells
HIV causes AIDS by killing interfering with normal functioning of helper T cells
Uninfected Person normally has between 800 and 1200 helper T cells in each mm2 of blood
In a person suffering from AIDS this number can be as low as 200mm3
T helper cells are important in cell mediated immunity
Without sufficient number of helper T cells, immune system cannot stimulate B cells to produce antibodies or the cytotoxic T cells that kill cells infected by pathogens
Memory cells become infected and destroyed; results in the body being unable to produce an adequate immune response; becomes susceptible to other infections and cancers
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What happens to people with HIVAIDS?
Many AIDS sufferers develop infections of the lungs, intestines, brain and eyes, experiencing weight loss and diarrhoea
It’s these secondary diseases that cause death
HIV doesn’t kill individuals directly, it does so by affecting the immune system
HIV prevents it from functioning normally; unable to respond effectively to other pathogens; causes infection/death
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What does ELISA stand for
Enzyme linked immunosorbant assay
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What’s the ELISA test used for?
It uses antibodies to not only detect the presence of a protein in a sample but also the quantity
It’s extremely sensitive
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Procedure for ELISA
1. Apply sample to a surface, e.g. a slide to which all antigens in sample will attach
2. Wash the surface several times to remove any unattached antigens
3. Add the antibody that is specific to the antigen we are trying to detect and leave the two to bond together
4. Wash the surface to remove excess antibody
5. Add a second antibody that binds with the first antibody. This second antibody has an enzyme attached to it
6. Add the colourless substrate of the enzyme. The enzyme acts on the substrate to change it into a coloured product
7. The amount of the antigen present is relative to the intensity of colour that develops
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What can the ELISA test be used to detect
HIV and the pathogens of diseases including tuberculosis and hepatitis.
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Why antibiotics are ineffective against viral diseases like AIDS
Antibiotics work in a number of different ways. One is by preventing bacteria from making normal cell walls.
In bacterial cells, as in plant cells, water constantly enters by osmosis. This entry of water would normally cause the cell to burst. That it doesn’t burst is due to the wall that surrounds all bacterial cells. This wall is made of murein, a tough material that is not easily stretched. As water enters the cell by osmosis, the cell expands and pushes against the cell wall. Being relatively inelastic, the cell wall resists expansion and so halts further entry of water.
Antibiotics like penicillin inhibit certain enzymes required for the synthesis and assembly of the peptide cross linkages in bacterial cell walls. This weakens the walls, making them unable to withstand pressure. As water enters naturally by osmosis, the cell bursts and the bacterium dies
Viruses rely on the host cells to carry out their metabolic activities and therefore lack their own metabolic pathways and cell structures. As a result antibiotics are ineffective because there are no metabolic mechanisms or cell structures for them to disrupt. Viruses also have a protein coat rather than a murein cell wall and so do not have sites where antibiotics can work. In any case, when viruses are within an organism’s own cells, antibiotics cannot reach them
