IMMUNITY

Large particles like bacteria can be digested by phagocytes which are a type of white blood cell and is a non-specific response. Phagocytosis:

1. Phagocyte is attracted to pathogen/ dead damaged abnormal cell by their chemical products. It moves to the pathogen along a concentration gradient.

2. Phagocyte has several receptors on its cell surface membrane which attach to the chemicals on the surface of the pathogen

3.The pathogen is engulfed into the bacteria by invagination of the cell wall to form a phagosome ( pathogen-containing vesicle) 

4. Lysosomes fuse to the phagosome and relase the lysozymes they contain. These destroy the pathogen by ingesting their cell wall. 

5. The products of the digestion of the pathogen are absorbed into the cytoplasm of the phagocyte.

Immunity is the ability of organisms to resist infection by protecting against disease-causing microorganisms or their toxins that invade the body. It involves the recognition of foreign material such as antigens. The initial response of the body when a pathogen infects it is non-specific. The next phase is the primary immune response which confers immunity. 

An antigen is any part of an organism that is recognised as non self by the immunse system and stimulates an immune response, Antigens are usually proteins that are on the cell-surface membrane or cell wall of invading cells like microorganisms or abnormal cells like cancer cells. The presence of an antigen triggers the production of an antibody as part of the body's defence system. 

Immunse responses like phagocytosis are non-specific  and occur WHATEVER the infection. The body also has specific responses that react to specific antigens. They are slower in action at first but can provide long-term immunity. The specific immune response depends on the type of white blood cell called a lymphocyte. Lymphocytes are produced by stem cells in the bone marrow. 

Specific lymphocytes aren't produced in response to an infection- they already exist, all 10 million types. When a pathogen enters the body one of these lymphocytes will have the correct specific protein on its surface that is complementary to one of the proteins of the pathogen. In other words the lymphocyte will " recognise" the pathogen. There are so many different types of lymphocytes present in the body, so there are very few of each lymphocyte. When an infection occurs the one type already present in the body that has the complementary proteins to those of the pathogen is stimulated to divide by mitosis to build up its number to a level that is efficient in destorying the pathogen. This is clonal selection and clonal expansion. 

There are two kinds of lymphocytes: B lymphocytes and T lymphocytes. B lymphocytes mature in the bone marrow and are associated with humoral immunity which is immunity involving antibodies that are present in the body fluids like blood plasma ( " humour") T lymphocytes mature in the thymus gland. They're associated with cell-mediated immunty ( immunity involving body cells)

Lymphocytes can respond to an organism's own cells that have been infected by a non-self material from a different species like virus. They also respond to cells from other individuals of the SAME species because they're genetically different and will have different antigens from the antigens on the cell surface membrane of the organism's own cells. T lymphocytes can distinguish these invader cells ( virus or same-species invader) from normal cells because :phagocytes that have engulfed and hydrolsed a pathogen present some of the pathogen's antigens on their 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 membranes

cancer cells are different from normal body cells and present antigens on their cell-surface membranes

cells displaying foreign antigens on their cell-surface membranes are called antigen-presenting cells 

T-lymphocytes ( lymphocytes that mature in the thymus gland) will only respond to antigens that are presented on a body cell ( rather than to antigens within the body fluids which B cells deal with)

This type of response is called cell-mediated immunity or the cellular response. The role of the receptors on T cells is important because the receptors on each T-cell respond to a single antigen. This means there are vast numbers of different types of T-cells, each one responding to different antigen. Cell-mediated immunity:

1. Pathogens invade body cells or are taken in by phagocytosis

2. The phagocyte places antigens from the pathogen on its cell surface membrane ( or infected body cells present antigen of the virus)

3. receptors on the specific T helper cell fit exctly onto these antigens

4. This attatchment activates the T cell to divide rapidly by mitosis and form clones 

5. The cloned T cells can: develop into memory cells enabling a rapid response to future infections by the same pathogen  

stimulate phagocytes to engluf pathogens by phagocytosis 

stimulate B cells to divide and become plasma cells                        activate cytotoxic T 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 by all substances so the cell dies by lysis.

Cytotoxic T cells are more effective against viruses because viruses replicate inside cells. As viruses use living cells in which to replicate the sacrifice of these infected cells prevents the virus multiplying and infecting more cells.

Some T cells provided by the mitotic division of specific T cells in the first phase of the specific response produce factors that stimulate B cells to divide. These B cells are involved in the next phase of the immune response which is humoral immunnity. 

Humoral immunnity is called this due to it involving antibodies and antibodies are soluble in the body fluids. There are as many as 10 million kinds of B cells, and each B cell starts to produce a specific antibody that responds to one specific antigen. When an antigen like a protein on the surface of a pathogen ( proteins are usually relied on to recognise cells because they have such a huge variety in their specific 3D structure) foreign cell, toxin, damaged or dead or abnormal cell enters the blood or tissue fluid there will be one B cell that has an antibody on its surface that fits the antigen- they are complementary. The antibody therefore attaches to this complementary antigen. The antigen enters the B cell by endocytosis and gets presented on the surface of the B cell ( processed)

T helper cells then bind to these processed antigens and stimulate the B cell to divide by mitosis to form clones of identical B cells which all produce an antibody specific to the foreign antigen. This is clonal selection and is the reason as to how the body can respond rapidly to a vast number of antigens. 

A typical pathogen has many different proteins on its cell surface membrane which can all act as antigens- antigens are ANY PART of an organism that is recognised as foreign (non-self) by the immune system and stimulates an immune response. Some pathogens like types of bacteria ( bacteria causing e.coli and cholera) produce toxins. Every toxin molecule acts as an antigen. Because of this many different B cells make clones which each produce its own type of antibody. As every clone produces ONE specific antibody these antibodies are called monoclonal antibodies.Every clone differentiates into one of two types of cells:

1. PLASMA CELLS secrete antibodies usually into blood plasma. These cells only survive for a few days but each can make around 2000 antibodies every second during its lifetime. These antibodies can lead to the destruction of the antigen they are complementary to. Plasma cells are therefore responsible for the immediate defence of the body against infection. The production of antibodies and memory cells are known as the primary immune response. 

2. MEMORY CELLS are responsible for secondary immune response. Memory cells live considerably longer than plasma cells do, often for decades. These cells do not produce antibodies directly. They circulate in the blood and tissue fluid. When they encounter the same antigen at a later date they divide rapidly and differentiate into plasma cells and more memory cells. The plasma cells produce the antibodies required to destroy the pathogen, whilst the new memory cells continue to circulate in preperation for a future infection. An increased quantity of antibodies is secreted at a faster rate than in the primary response so a new infection is destoryed before it can cause harm.

1. A specific B cell has an antiboy on its surface that perfectly fits the shape of the antigen of the pathogen that has infected the body. The antigen attaches to this antibody.

2. The B cell processes the antigens and presents them on its surface. 

3. Helper T cells attach to the processed antigens on the B cell and activate the B cell

4. The B cell is activated to divide by Mitosis and to form many clones of plasma cells.

5. The cloned plasma cells produce and secrete the specific antibody that exactly fits the antigen on the pathogens surface.

6. The antibodies produced attaches to antigens on the surface of the pathogen and destroy the pathogen. 

7. Some B cells develop into memory cells. The production of antibodies from plasma cells and memory cells are called the primary immune response. These can respond to future infections by the same pathogen by dividing rapidly and developing into plasma cells that produce antibodies to kill the pathogen. This is the secondary immune response and provides long lasting immunity. The memory cells can circulate in the body for years. When memory cells divide and produce plasma cells they also produce new memory cells which continue to circulate in the body fluids ( usually blood plasma)

Antibodies are proteins that have specific binding sites and are synthesised by B cells. When the body is infected by a non-self material a B cells produces a specidic antibody to combat this. This specific antibody reacts with an antigen on the surface of the non-self material by binding to them. Each antibody has two identical binding sites. The antibody binding sites are complementary to a specific anitgen. The massive variety of antibodies is possible becauese they are made of proteins which are molecules that have a massive variety of specific 3-D shapes. 

Antibodies are made up of 4 polypeptide chains- 2 are long and so called heavy chains, 2 are short and are called light chains. Each antibody has a specidic binding site that fits very precisely onto a specific antigen to form a ANTIGEN-ANTIBODY COMPLEX. The binding site is different on different antibodies so is called the variable region. Each binding site consists of a seqence of amino acids that form a specific 3D shape that binds directly to a specific antigen. The rest of the antibody is known as the constant region as it stays the same with each antibody. This binds to receptors on cells like B cells. 

Antibodies do not destory antigens directly but rather prepare the antigen for destruction. Different antibodies lead to the destruction of an antigen in a range of ways

If the antigen is a bacterial cell-

1. Antibodies cause agglutination of the bacterial cell. This is where each antibody attaches to two bacterial cells to cause them to clump together. In this way clumps of bacterial cells are formed which make it easier for phagocytes to locate them as they are less spread out within the body.

2. They then serve as markers that stimulate phagocytes to engulf the bacterial cells to which they are attached. 

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 tpe of B cell to multiply by mitosis and form clones of itself. Each of these clones will produce a different antibody. It's very medically important to be able to produce antibodies outside of the cell. It's even better if one single type of antibody can be isolated and cloned. Such antibodies are monoclonal antibodies. Monoclonal antibodies have several useful functions in science and medicine. 

1. Targeting medication to a specific cell type by attaching a therapeutic drug to an antibody. 

As an antibody is very specific to a particular antigen ( protein) 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. The most sucesesful is direct monoclonal antibody therapy.

- monoclonal anitbodies are produced that are specific to antigens on cancer cells

-These antibiotics are given to a patient and attach themselces to the receptors on their cancer cells.

-They attach to the surface of their cancer cells and block the chemical signals that stimulate their uncontrolled growth. 

Herceptin is a monoclonal antibody used to treat breast cancer. The advantage of direct monoclonal antibody therapy is that since the antibodies aren't toxic and are highly specific they lead to fewer side effects that other forms of therapy can produce. 

Another method is called indirect monoclonal antibody therapy, which involves attaching a radioactive or cytotoxic drug to the monoclonal antibody. When the antibody attatches to the cancer cell it kills them. There monoclonal antibodies are called " magic bullets" and can be used in smaller doses as they are targeted on specific sites. Using them in smaller doses is cheaper and reduces any side effects the drug might have. 

2. Medical diagnosis 

Monoclonal antibodies are an invaluable tool in diagnosing disease with more than a hundred different diagnostic products based on them. They are usd for the diagnosis of influenza, hepatitis and chlamydia infections where they produce a much m ore rapid result than convential methods of diagnosis. They are important in diagnosing certain cancers. Men with prostate cancer often produce more of a protein called prostate specific antigen ( PSA) leading to unusally high level of it in the blood. By using monoclonal anitbodies that intereacts with this antigen it is possible to obtain a measure of the level of PSA in the blood. A higher level of PSA is not itself a diagnosis of the disease but gives an early warning of its possibility and the need for futher tests.

- PREGNANCY TESTING

It's important that a mother knows as early as possible that she is pregnant. The use of pregnancy testing kits that can easily be used at home has made it possible to detect pregnancy early on. These kits rely on how the placenta produces a hormone called human chorionic gonadatrophin ( hCG) and this is found in the mother's urine. Monoclonal antibodies on the test ***** of a home pregnancy testing kits are linked to coloured particles or dye. The hCG antibody colour complex complex moves along the ***** until it is trapped by a different kind of antibody containing an enzyme which " sandwhiches" the hCG and produces a colour change when the dye of the first antibody reacts with the enzyme of the second, producing a colour change. 

The devlopment of monoclonal antibodies has provided society with the power and opportunity to treat diseases in before unknown ways. They also help to diagnose several different illnesses.  However the production of monoclonal antibodies raises ethical issues

1. Production of monoclonal antibodies involves the use of mice. The mice are used to produce both antibodies and tumour cells. The production of tumour cells involves delibaretly inducing cancer in mice in order to produce an antibody with the correct specific shape to attach to the surface antigens of these cancer cells. There are specific guidelines drawn up to minimise any suffering, but some people disagree with this treatment of animals.

2. Monoclonal antibodies have been sucessfully used to treat a number of diseases including cancer and diabetes which saved many lives. There have also been deaths assocatied with their use in the treatment of MS. It's important that patients have full knowledge of the risks and benefits of these drugs before giving permisiion for them to be used ( informed consent)

3 Tests for the safety of the new drugs present dangers. In March 2006 6 healthy volunteers took part in the trial of a new kind of monoclonal antibody in London. Within minutes they sufferent multiple organ failure which is probably a result of T cells overproducing chemicals that stimulate an immune response or attacking the body tissues. All the volunteers survived but it raised issues over the testing of new monoclonal antibodies on people.

Passive immunity is produced by introduction antibodies into invidiuals from an outside source- you give the body antibodies. No direct contact with the pathogen or its antigen is required to induce immunity. Immunity is immediate. As the antibodies are not being produced by the individuals themselves the antibodies are not replaced when they're broken down, no memory cells are formed and there's no long-lasting immunity. Examples of passive immunity: anti-venom given to the victimes of snake bites and the immunity required by the fetus when antibodies pass across the placenta from mother to child. 

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. It is generally long lasting and is of two types-

Natural active immunity- results from an individual becoming infected with a disease under normal cirumstances. The body produces it's own antibodies and can continue to do so for years. 

Artificial active immunity- forms the basis of vaccination. Involves inducing an immune response in an individual without them suffering symptons of the disease. 

Vaccination is the introduction of the appropiate 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 the vaccine and in whatever form it contains one or more types of antigens 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 results is that there is a rapid production of antibodies and the new infection is rapidly overcome before it can cause any harm with few if any symptons. 

When vaccination is carried out on a large scale it provides protection against diease for both individuals and whole populations.

It's important to understand that vaccination is used as a precuationary measure to prevent individuals contracting a disease. It isn't used to treat individuals who already have the disease. Some programmes of vaccination against disease has been sucessful. In other instances similar measures have been less sucessful. The sucess of a vaccination programme depends on:

1. A suitable vaccine must be economically available in sufficient quantities to immunise most of the vunerable population.

2. There must be a few side effects, if any, from vaccination. Unpleasant side-effects may discourage individuals in the population from being vaccinated. 

3. Means of producing, storing and transporting the vaccine must be available. This usually involves technologicalaly advanced equipment, hygenic conditions and refrigerated transported. 

4.There must be means of administering the vaccine properly at the appropiate time. This involves training staff with appropiate skills at different centres throughout the population.

5. It must be possible to vaccinate the vast majority of the vunerable population to produce 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 the popultion. This concept is based on the idea that individuals can pass pathogens to other individuals when in close contact with them. Where the vast majority of the population is immune it is improbable that someone who is not immune to the pathogen will actuall come into contact with an infected person. In this way those indivudals who aren't immune to the disease are still protected.

Herd immunity is important because it isn't possible to vaccinate everyone in a large population. Babies and very young peope cannot be vaccinated because their immune systems are not yet fully functional. It could also be dangerous to vacciante those who are ill or have a compromised immune system. The percentage of a population that has to 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 for a certain period there are very few individuals in the population with the diesase and the transmission of the pathogen is interupted. 

Even when the criteria for sucessful vaccination are met, it can still prove extremely difficult to eradicate a disease. The reasons:

1. Vaccination fails to induce immunity in certain individuals like people with defective immune systems. 2. Individuals may develop disease immediately after vaccination but before their immunity levels are high enough to prevent it. These individuals can habour the pathogen and infect others with it.

3. The pathogen may mutate frequently so that its antigens change suddenly rather than gradually. This means the vaccines suddenly become ineffective against the new antigens on the pathogen and the antigens are no longer recognised by the immune system. As a result, the immune system does not produce the antibodies to destory the pathogen. This is called antigenic variability. It happens with the influenza virus which changes its antiigens frequently. Immunity is therefore short-lived and indivudals may develop repeated bouts of influenza during their lifetime.

4. There are so many varieties of a particular pathogen that it is almost impossible to develop a vaccine that is effective against them all. For example there are over 100 varieties of the common cold virus and new ones are constantly evolving. 

5.Certain pathogens " hide" from the body's immnune system, either by concealing themselves inside cells or living in places out of reach like within the intestines- like the cholera pathogen.

6. Individuals may have objections to vaccination for religious, ethical or medical reasons. For example, unfounded concerns over the measels, mumps and rubella triple vaccine ( it was said the triple vaccine caused autism in children) has led a number of parents to opt for seperate vaccinations for their children, or to avoid vaccination altogether.

The human immunodeficiency virus causes the disease acquired immunne deficiency syndrome ( AIDS) Among contagious diseases it is a relative newcomer having first been diagnosed in 1981.

STUCTURE OF HIV- On the outside is a lipid envelope which have peg-like attatchment proteins embedded into it. Inside the envelope is a protein layer called the capside that encloses two single strands of RNA and some enzymes. One of these enzymes is reverse transcriptase which is called this because it catalyses the production of DNA from RNA which is the reverse reaction to what is carried out by transcriptase. The presence of reverse transcriptase and consequent ablity to make DNA from RNA, means that HIV belongs to a group of viruses called retroviruses. 

Being a virus, HIV cannot replicate itself. Instead it uses its genetic material to instruct the host cell's biochemical mechanisms to produce the components required to make new HIV. 1. Following infection HIV enters the bloodstream and circulates around the body. 2. A protein on the HIV readily binds to another protein called CD4. This protein occurs on many different cells, but HIV most often attached to helper T cells.

3. The protein capsid fuses with the cell-surface membrane of the helper T cell. The RNA and enzymes of HIV enter the helper T cell.

4. The HIV reverse transcriptase converts the virus' RNA into DNA.

5.The newly made DNA is moved into the helper T cell's nuclues where it is inserted into the cell's DNA.

6. The HIV DNA in the nuclues creates messenger RNA ( mRNA) using the cell's enzymes. This mRNA contains the instructions for making new viral proteins and the RNA to go into the new HIV

7. The mRNA passes out of the nucleus through a nuclear pore and uses the cell's protein synthesis mechanisms to make HIV particles

8. The HIV particles breakk away from the helper T cell with a piece of its cell-surface membrane surrounding them which forms their lipid envelope.

Once infected with HIV a person is said to be HIV positive. However the replication of HIV often goes into dormancy and only reccomences, leading to AIDS, many years later.

The human immunodeficiency virus specifically attacks helper T cells. HIV causes AIDS by killing or interfering with the normal functioning of helper T cells. An unifected person normally has between 800-1200 helper T cells in each mm cubed of blood. Someone who has AIDS this number can be as low as 200. Helper T cells are important in cell-mediated immunity. WIthout a sufficient number of helper T cells the immune system cannot stimulate B cells to produce antibodies or the cytotoxic T cells that kill cells infected by pathogens. Memory cells may also becomme infected and destroyed. As a result the body is unable to produce an adequate immune response and becomes susceptible to other infections and cancers. Many AIDS sufferes develop infections of the lungs, intestines, brain and eyes, as well as experiencing weight loss and diarrhoea. It is these secondary diseases that ultimately cause death.

HIV doesn't kill individuals directly. By infecting the immune system HIV prevents it from functioning normally. As a results those infected by HIV are unable to respond effectvely to pathogens that infect their body. It is these infections rather than HIV that ultimately cause ill health and eventual death.

ELISA stands for enzyme linked immunosorbant assay. It uses antibodies to not only detect the presence of a prtoein in a sample but also the QUANITIY. It is extremely sensitive and so can detect very small amounts of a molecule. Imagine you're trying to find a particular antigen in a sample-

1. Apply the sample to a surface, for example a slide to which all the antigens in the sample will  attatch.  2. Wash the surface several times to remove any unnattaced antigens  3. Add the antibody that is specific to the antigen you are trying to find and leave the two to bind together. 4. Wash the surface to remove excess antibody. 5. Add a second antibody that binds with the first antibody. The 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 developes. 

This basic technique can be used to detect HIV and the pathogens of diseases like TB and hepatitis. ELISA is especially useful where the quantity of an antigen need to be measured. In testing for particular drugs in the body for example: the mere presence of a drug is often less important than its quantity as many drugs are found in low concentrations. It is used in drugs and allergens tests.

In bacteral cells water is costantly entering by osmosis. This entry of water would normally cause the cell to burst. However it doesn't because bacterial cells are surrounded by a cell wall made of murein which is a tough inelastic material. As water enters the cell by ismosis the cell expands and pushes against the cell wall which will resists further expansion and halts futher entry of water. Antibiotics such as penicillin work by inhibiting certain enzymes required for the synthesis and assembly of the peptide cross linkages in bacterial cell walls. This weakens the cell walls and makes them unable to withstand pressure. Thus as water enters the bateria 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 don't have sites where antibiotics can work. What's more when viruses are within an organisms own cell antibiotics cannot reach them.