The use of monoclonal antibodies in enabling the targeting of specific substances and cells. • evaluate methodology, evidence and data relating to the use of vaccines and monoclonal antibodies • discuss ethical issues associated with the use of vaccines and monoclonal antibodies.

So... what are monoclonal antibodies?
Monoclonal just means a group of the same thing, so when we talk about monoclonal antibodies we mean a whole load of antibodies that are exactly the same. This is significant because inside the body, you find many different types of antibodies: this is because B cells which produce antibodies are induced to clone by antigens on the surface of a pathogen, there are many different antigens on a single cell, so many different B cells are produced and hence many different antibodies (polyclonal).

How are they made?
There now several ways to produce monoclonal antibodies, the one below is Milstein and Kohlers method (1975):

1. Introduce a pathogen (with complimentary antigens to the antibody you want) to a mammal.
2. The antigen will induce the cloning of the B cell that produces the right antigen. However, it will also produce others, giving B cells that will produce polyclonal antibodies.
3. The B cells are taken out of the body and fused with tumour cells. The result is a hydribomas which is a cells that produces antibodies but can live for a longer time and divide outside the body.
4. Different hybridoma are separated off and left to divide until it forms a group (a clone).
5. Each clone is screened for the antibody that is needed- if it is being produced then it is grown on an industrial scale.
6. Antibodies are extracted from the clone.

What are they used for?

Monoclonal antibodies are useful in the treatment of illness and the application of science because they allow the targeting of specific cells due to the fact that they will only bind with one antigen.

• Separation techniques.
• Immunoassay: when you take a pregnancy, drugs or HIV test, there are complimentary monoclonal antibodies in the test which will form an antigen-antibody complex with the protein that is being looked for which triggers a colour change.
• Cancer therapies: trigger the immune system to attack cancer cells; carry radiation to the cancer cells; block signals that tell the cancer cells to divide.
• Preventing rejection of transplanted organs: by targeting the T cells involved with destroying the foreign tissue.
• Diabetes treatment.

What are the associated ethical issues?

• You have to give cancer and illness to mammals (mice).
• You have to make transgenic mammals (giving the properties of humans to make the antibodies suitable to use in the treatment of people).
• Testing on humans caused organ failure.
• Some people with MS have died as a cause.

The use of vaccines to provide protection for individuals and populations against disease. • evaluate methodology, evidence and data relating to the use of vaccines and monoclonal antibodies • discuss ethical issues associated with the use of vaccines and monoclonal antibodies • explain the role of the scientific community in validating new knowledge about vaccines and monoclonal antibodies, thus ensuring integrity • discuss the ways in which society uses scientific knowledge relating to vaccines and monoclonal antibodies to inform decision-making.

Vaccines involve injecting a weak or inactive form of a pathogen into the body.

The antigens stimulate an immune response from white blood cells.

The cells destroy the pathogen, but more importantly, they also produce memory cells.

This means that if the real pathogen enters the body, memory cells will produce large amounts of plasma cells very quickly to combat the pathogen- so it is destroyed before it can harm the body.

This is often carried out throughout whole populations so that everyone is protected against a pathogen and it can be eradicated.

Using a weak or inactive form of the pathogen means that there is no risk of the pathogen from the vaccine harming the body.

The MMR vaccine
A vaccine that protects against Measles, Mumps and Rubella is given to all children in the UK to prevent them getting these potentially disabling diseases. Andrew Wakefield published a study on the vaccine in 1998 which appeared to show that it increased the risk of children getting autism.

The claims are now believed to be completely unfounded in light of: new research showing no link; the small sample size he used; his vested interest to prove the link for the Legal Aid Board. However, at the time there was a big following of this idea and many people decided not to vaccinate their children. As a result the cases of all three diseases rose.

Ethical issues

• Testing on animals
• Potentially harmful testing on humans
• Possible side effects
• The fact that it might breach peoples rights to make vaccines compulsory

The effects of antigenic variability in the influenza virus and other pathogens on immunity.

Some pathogens have many different strains.

Influenza (common flue) is an example of a pathogen with multiple strains.

The different strains have different antigens- this is known as antigenic variability.

Memory cells will recognise antigens they have seen before and tackle a pathogen before symptoms arise- this is why you can only get chicken pox once.

However, if the antigen is different, the memory cell will not recognise it and be able to destory it.

This means that it is down to the slower and less effective primary response to kill the pathogen, allowing time for the pathogen to harm the body and cause symptoms- this is why you can get influenza multiple times.

The essential difference between humoral and cellular responses as shown by B cells and T cells. The role of plasma cells and memory cells in producing a secondary response.

Lymphocytes are white blood cells. They are created as stem cells in the bone marrow. They have defences that are specific to the pathogen they are attacking (unlike phagocytes which do the same for everything) which makes response slower, but more effective long term.

B cells

• mature in the bone marrow
• respond to antigens in the bodies fluids: tissue fluid; blood (humoral response)
• produce antibodies
• produce memory cells

1. ingest pathogen and present antigens on the surface
2. these are recognised by helper T cells, which stimulate mitosis
3. plasma cells and a Memory cells are produced
4. plasma cells secrete antibodies which attach to antigens on a pathogen to destroy it (primary response)
5. memory cells stay in the blood stream for many years, if they encounter the same pathogen again, they can divide rapidly and with greater intensity to make plasma cells which will make antibodies (secondary response)

The secondary response provides long term protection as they memory cells stay alive for many years. They produce many more plasma cells and are much faster at doing so than the primary response, this means that the pathogen can be fought before it causes harm to the body.

T cells

• mature in the thymus glands
• recognise antigens if presented on the surface of other cells (cell-mediated response)
• stimulate b cells and phagocytes
• kill infected cells
• produce memory cells

1. Phagocytes, infected cells and cancer cells all display antigens on their surface
2. A specific helper T cell will have receptors that fit exactly with the antigens- when they meet, the helper T cell stimulates other T cells to form appropriate clones by mitosis
3. These T cells can: stimulate B cells; stimulate phagocytes; develop into memory cells; kill cells
4. They kill cells by producing a protein which breaks cell-surface membranes.

Antibody structure and the formation of an antigen-antibody complex.

Antibodies are often compared to a Y shape because of their one receptor binding site and two pathogen binding sites.

Antibodies are made of two different polypeptide chains, a light chain and a heavy chain. They are attached to each other, but can move in the pathogen binding site to help bind to the pathogen.

The variable region is different on different types of antibody because it needs to be specific to the antigen it is targeting. The constant region is the same in all antibodies.

The variable region has a tertiary structure that is complimentary to (fits with) that of the antigen it is aiming to destroy- this is so that the two can bind and form what is known as an antigen-antibody complex.

wikipedia

Definition of antigen and antibody.

An antigen is a 'marker' on a cell that is foreign to the body that identifies it as non-self.

An antibody is a protein produced by the body to destroy pathogens.

Phagocytosis and the role of lysosomes and lysosomal enzymes in the subsequent destruction of ingested pathogens.

Phagocytes are white blood cells. They destroy bacteria by engulfing them and breaking them down- this process is called phagocytosis.

The phagocyte recognises a pathogen because of its chemical products and so moves towards it.

It then binds with the pathogen and begins to engulf (wrap around) it- by doing this it forms a vesicle (sac) with the phagocyte inside it know as a phagosome.

Lysosomes (vesicles with enzymes inside) release digestive enzymes into the phagosome, this means that it can be broken down. Useful products are absorbed by the cell and others are excreted.