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Using Math to Help the Immune System Fight Cancer
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T cells and B cells, the white blood cells of the adaptive immune system that help fight infectious agents and cancerous cells, have an amazing repertoire of proteins they can make. There are hundreds of thousands of cell surface receptors that T cells and B cells can make in order to recognize the huge variety of antigens the host is presented with. This is an amazing accomplishment, given that the human genome only has about twenty thousand unique genes. Each T cell or B cell is capable of making only one receptor, specific to one particular antigen. In order to make the huge variety of receptors needed for these adaptive immune cells, different portions of the gene encoding the receptor are combined together the make the receptor. For example, in human T cells, most T cell receptors (TCR) are composed of two recombinant chains, an α chain and a β chain. The α chain is made by combining two random segments, one called a V segment, for variable, and the other a J segment, for joining. The β chain is made by combining a random V segment, a random D segment, and a random J segment. The two randomly made chains will join together to form the final TCR. There are many possible V, D, and J segments that can be combined together for each chain, and the pairing of the α and β chains is random. This ensures a very high diversity of TCRs in the human host, so that a huge variety of pathogens can be recognized and killed by the immune system.

After the T cell has encountered antigen through its TCR, the T cell will then replicate rapidly in response. This is called clonal expansion, because all of the new T cells will have the same TCR. The T cell will work to kill the offending pathogen. After the pathogen has been removed from the host, the T cells will decrease to lower numbers again. Some of the clonally expanded T cells will remain as memory cells, which can quickly be activated and replicate if the antigen is encountered in the future. This is how a memory response develops in the host. The memory T cells help form the TCR repertoire, which is the collection of TCRs in the host.

The random recombination of V, D, and J segments, and random pairing of α and β chains means that different individuals will have differing repertoires of TCRs. This means that a TCR from one individual that recognizes a specific antigen may differ from the TCR of another individual recognizing the same antigen. However, because the antigens are the same, it is expected that certain portions of the TCR will also be similar between these individuals. Scientists from Virginia Commonwealth University Massey Cancer Center have recently begun characterizing the T cell repertoire in volunteers in order to analyze these patterns, which are called fractals. Fractals are patterns that can be found in nature, that repeat themselves over a variety of scales. These repeated patterns only need to be similar to each other, not completely identical.

By examining the fractal patterns among TCRs, researchers hope to find connections between the receptor being produced by the T cell, and the antigen being recognized. They hope to use this information in selecting appropriate donors for cancer patients receiving bone marrow transplants. By analyzing the fractal patterns among T cells, researchers want to find specific cells that will be efficient at destroying the cancer and improving the patient’s immune repertoire. In addition, they believe that comparing fractal patterns between the donor and the patient can help prevent complications such as transplant rejection and graft versus host disease.

When the researchers analyzed fractal patterns of TCRs from bone marrow donors, they found similar patterns, with a great deal of diversity amongst the TCRs. The donors had similar usage of specific V, D, and J segments in their TCRs as well. The patients who were receiving the bone marrow, however, had significantly less variability in their TCR repertoire. The lack of diversity indicates that fewer damaging antigens, which are produced by infectious agents and caner cells, can be recognized and killed by T cells. By using these fractal patterns, the researchers can find complimentary donors who can contribute to the patient’s repertoire. The researchers hope to optimize the benefits received from a bone marrow stem cell transplant. They add that they believe that the immune system can be improved in the patients. This could help speed recovery after bone marrow transplants.


References:

http://www.sciencedaily.com/releases/201...091849.htm

http://mathworld.wolfram.com/Fractal.html
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