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Antibodies and antigens


The antigen-antibody reaction

Antibodies are "natural" chemicals produced by the body's immune system in response to infecting micro-organisms.
Do not confuse antibodies with antibiotics.
What is the difference between antibodies and antibiotics?
Antibodies are produced by the (human/whatever) body "naturally" in response to specific "foreign" cells - bacteria or viruses.
Antibiotics are produced by micro-organisms cultured by Man, then processed and administered in a general (hopeful!) way by a doctor as a drug, in order to kill or prevent the reproduction of bacteria - but they are ineffective against viruses.

More specifically, each antibody is produced by lymphocytes (specialised white cells) as a result of exposure to specific chemical substances (mainly proteins and carbohydrates) called antigens, usually on the outside of an invading organism. This is called the antigen-antibody reaction. So-called B-cell lymphocytes produce the antibodies, in response to T-cells (there are several sorts) which participate more directly in recognising the foreign cells, and chemically damaging them. The antibodies are proteins ("immunoglobulins") which are transported around the body in the bloodstream as part of the plasma protein.
What body system do lymphocytes originate from, and what other functions does that system perform?
lymphatic system - lymph vessels and lymph nodes, spleen & thymus - closely related to the blood circulatory system
also functions in processing of products of digestion of fats & oils (lipids) - connected to the lacteals inside villi in the small intestine (ileum)

What name is given to the outside layer of viruses and what is it composed of, chemically?
capsid - protein or envelope - protein, lipid, carbohydrate?
What name is given to the outside layer of bacteria and what is it composed of, chemically?
cell wall - protein and carbohydrate
Antigen-antibody response At the molecular level, antibodies are known to be shaped like the letter Y, with a reactive site at the tip of each branch, so that antibodies can become attached to antigens on the basis of their molecular shape, rather like an enzyme and substrate. This can cause the infecting micro-organisms to stick together, and neutralises them until they are taken away and dealt with by other white cells.
What name is given to the other white cells, and how do they deal with the infecting micro-organisms?
phagocytes - engulf (ingest and digest) them!
The production of antibodies can be used to explain
- normal recovery from infection by bacteria or viruses - the primary immune response
- immunity to a subsequent infection by the same organism - the secondary immune response
- susceptibility to other micro-organisms (or different varieties or strains of the same micro-organism).
Why is there a gap (in time) between first infection and recovery?
It takes some time for the chain of events: recognition of invaders,cell division to make adequate numbers of the lymphocytes which produce the correct antibodies.
How can antibodies explain immunity to subsequent infection?
Some white cells ("memory cells") remain after "beating" an infection and are able to divide rapidly to produce more lymphocytes which will produce the correct antibodies, so that the infection is quickly dealt with (or not even noticed).
Why are we susceptible to other (i.e. different) infecting micro-organisms, after our body has "fought off" an infection?
Because other micro-organisms have different antigens, and the immune system must start again from scratch.
Why do common diseases like the cold, and flu, sometimes come back again year after year, often as epidemics?
Different strains have different antigens on the outside, so the body's immune system may not be prepared for that specific strain, so that it can get into cells and reproduce.
Why is there great concern about the emergence of antibiotic-resistant strains of more virulent disease such as tuberculosis?
The body's immune system alone was not enough to prevent epidemics of these diseases, and treatment with antibiotics tipped the balance in our favour. If strains of these pathogens are selected due to improper use of antibiotics, there will be fewer medical alternatives.
What is the difference (in biological terms) between immunity and resistance?
Immunity applies to a person or other organism who has an antibody-based protection against an infecting organism - bacterium or virus. Never say that a bacterium is immune to, or has immunity to, an antibiotic, for instance.
Resistance applies to the ability of a micro-organism to survive the effects of an antibiotic.
It is a property of the pathogenic micro-organism, not a weakness or chemical property of the antibiotic, and unrelated to the organism which is being infected - usually human or Man's stock animals. Since resistance to antibiotics is likely to be genetically based, there is fear that populations of resistant strains may become established. Never say that bacteria are spread, or grow - examiners prefer to be told that bacteria reproduce (asexually).

The antigen-antibody reaction is also the basis for immunisation programs (vaccination), in which exposure to a related, weakened or dead form of a pathogenic organism, or even parts of its outer coat, brings about an immune response which is similar to the body's normal reaction to the more powerful or virulent form which would be difficult to fight off. Both of these - natural infection and exposure to vaccine - result in active immunity.
Passive immunity is based on ready-made antibodies. For example babies obtain these from their mother's bloodstream and first milk (colostrum) . Passive immunity may also be obtained via serum - derived from blood of organisms exposed to a pathogen.
The specificity of this antigen-antibody reaction can be of even more use to Man when it is further refined and developed.

The development of monoclonal antibodies

The normal antigen-antibody reaction described above is often the result of several antibodies produced in response to several different antigens on the surface of an invading micro-organism. Since several different lymphocytes are involved in the production of a cocktail of antibodies, these are known as polyclonal antibodies.

A method of using the specificity of action of single antibodies in the lab was recently discovered by Cesar Milstein and co-workers, who made it possible to produce pure antibodies to almost any substance, to order.
However they had to overcome a problem that lymphocytes only survive inside a living body - they cannot be grown in the laboratory in the same way that some other cells can.

Abcell
In the laboratory, an animal, e.g. a mouse, is exposed to the foreign substance, which after a few days results in the production of a mixture of antibodies in response to the antigens responsible.
White cells are then extracted from the animal (actually from its spleen - an organ which regulates many of the functions of blood) and fused with cells taken from a cancerous tumour.
A detergent (which lowers the surface tension) is used, together with gentle agitation.
How will this assist in the fusion process?
By chemically disrupting the cell membrane (which contains lipids) - and physically bringing cells close together, allowing cytoplasm of tumour cells and lymphocytes to join together
Why is this fusion necessary?
This has to be done because antibody-producing cells do not live long or divide in laboratory culture, whereas cancer cells grow rapidly (the reason they cause the tumour in the first place).
The result is a collection of cells including hybrid (hybridoma) cells which must be separated into single cells and then given the opportunity to grow into groups.
Why is it a collection of cells, and why must they be separated out?
There will be some unfused lymphocytes, unfused tumour cells, and even some double fusions of the same type!
There are also likely to be several different antibody-producing lymphocyte-tumour hybrids.

Each group of cells is called a clone because it is derived from a single cell. These are then tested to see if they are producing antibodies for the particular target substance. Since they are genetically identical, all the cells produce the same antibody, which builds up in the nutrient medium surrounding the cells. This is easily purified, resulting in a product containing molecules of a single antibody - not a mixture. Since the final result is due to the action of many cells derived originally from a single lymphocyte cell, these are called monoclonal antibodies.
What is the name of the (nuclear) process that takes place as the (single) cells divide to make a clone?
mitosis



Potential applications of monoclonal antibodies


Due the the specificity of their binding properties, monoclonal antibodies may have a wide variety of possible uses.

Possibilities include the following:

- Identification of odd substances produced by the body in special circumstances, e.g. hormones produced in pregnancy, or abnormal metabolites which enable screening for genetic abnormalities, drugs, etc and other health problems.
What is the name of the hormone, produced in pregnancy, on which pregnancy testing is based?
human chorionic gonadotrophin (hCG)

- Identification and quantification of circulating micro-organisms, possibly in small numbers or too small to see under the microscope, e.g. infecting viruses.

- Industrial processing, either by concentrating products which are needed, or by removing unwanted substances. For example, blood products such as factor 8, which is needed by haemophiliacs, could be processed using monoclonal antibodies in such a way as to avoid viruses which may be present in only a small number of cases but which pose a major problem when blood products are produced from a pooled source.

- To target and identify, neutralise or remove unwanted substances from the body, especially the blood plasma. Examples might include drugs taken in overdose.

- If a particular type of cancer with cells widespread in the body can be shown to have different antigens than ordinary cells then it may be possible to treat cancer by targeting only the unwanted cells in the body. One way in which this could be done is by attaching poison to antibodies which will build up only in the cancer cells and killing them, whilst having more or less no effect on ordinary cells which have different antigens. The potent plant poison ricin has been investigated in this context.

- Reducing the possibility of rejection in transplants by more accurate tissue typing between recipient and possible donors.



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