Research updates
4 - Engineering antibodies page 1
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1. Introduction Link to the Medical Research Council web site
 
 
Monoclonal antibodies can be used to diagnose a wide range of disorders, such as cancers and viral infections, and they have been widely used in research. They have great potential in the treatment of diseases, but initially their use in humans was limited. This is because they originate from immunised mice and can trigger a dangerous immune response in patients.
Figure 1 
Figure 1. Dr Jacki Harrison is part of the research team.
MRC scientists have been working to solve this problem using genetic engineering. They have managed to 'humanise' antibodies by transferring a small region from the mouse antibody to an otherwise human antibody. A different approach has involved the creation of transgenic mice with human not mice antibody genes, allowing the production of pure human antibodies. Genetic engineering has also been used to produce artificial antibodies without immunisation. The availability of humanised and test tube antibodies heralds a new era in the use of monoclonal antibodies as therapeutics.
Background
A foreign invader - rally the defences! Multicellular organisms are able to discriminate between their own molecules and those of foreign invading microbes, that is, to distinguish 'self' from 'non-self'. Vertebrates have natural immunity, bringing into action their first line of defence, the phagocytic white blood cells. Also mobilised is a series of blood serum proteins known as the complement system.
The crack defence troops, however, are the antibodies. The presence in the body of a foreign molecule (antigen) can initiate the production of a counteracting molecule (antibody) which is highly specific to that particular antigen. This is known as acquired or specific immunity.
 
My antigens and yours
Antigens matter greatly in transplant surgery, when there must be a compatibility between donor and recipient tissues. Otherwise, there may be a severe immune response leading to rejection of the transplanted organ.

Phagocytic white blood cells are part of the immune response. Normally they attack invading bacteria by surrounding them and forming a vacuole. Vesicles containing digestive (lytic) enzymes then fuse with the vacuole and the bacterium is destroyed.

Successful blood transfusions depend on compatibility of the blood groups of donor and recipient. The different blood groups are determined genetically. They depend on the presence or absence of certain antigens, called A and B agglutinogens, on the surface of red blood cells. In general, in the blood plasma of a healthy person, there will not be antibodies (agglutinins) against the blood group antigens present on their own red blood cells. However, they will have antibodies to the blood group antigens not found on their own red blood cells. These could be anti-A or anti-B agglutinins.

Incompatible transfusions may bring A (or B) agglutinogens into contact with anti-A (or anti-B) agglutinins. The antibodies cause the transfused cells to agglutinate, and the transfusion can be fatal.

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Question 1

Use your knowledge of blood groups and the information that is already filled in to complete the table below:

blood
group
antigen on red blood cell membrane plasma
antibody
accepts blood
from
can donate
blood to
O none anti-A,B
A anti-B A, AB
B B, O
AB A, B none