the Studying Immune System and Cancer with Multivariate Statistics and Microarrays
Susan Holmes Statistics Department, Stanford University Collaboration with Peter P Lee from Stanfords Hematology Department Elizabeth Purdom, Statistics, Stanford. Work supported by the ACS and the NSF DMS grant 02-41246. Ban, August 19th, 2004 Thanks to Bioconductor contributors, in particular Sandrine Dudoit, Jean Yee, Wolfgang Huber.
A little immunology
T-lymphocyte cells (T-cells) originally derive from stem cells of the bone marrow. At around the time of birth, lymphocytes derived in this way leave the marrow and pass to the thymus gland in the chest, where they multiply.
The lymphocytes are processed by the thymus gland, so that between them they carry the genetic information necessary to react with a multitude of possible antigens.
Antigens
The human genome is presently estimated to contain as few as 25 thousand genes (we should soon know the number exactly). The number of T-cell receptors for antigen (TCRs) that we make is estimated at 25x106 Antigens are macromolecules that elicit an immune response in the body. Antigens can be proteins, polysaccharides, conjugates of polysacharides and proteins. T-cell diversity is attained by a complex 5-stage genetic rearrangement that occurs at random in the developing T-cells in the thymus. T-cells are tested for their ability to recognise and bond to antigens in the thymus. It is thought that this occurs by positive and negative selection.
The postulation is that positive selection eliminates T-cells that do not bond tightly enough to antigen type molecules produced in the thymus and negative selection eliminates T-cells that bond too tightly to self type molecules found in the thymus. This produces a mature T-cell that is eective against antigens but is
also self tolerant. It is known that approximately 95% of all developing T-cells die in the thymus. The T-cells, each processed to recognise and interact with a specic antigen, circulate permanently between the blood and lymphatic systems. On recognition of the antigen by a helper T-cell, one or a group of lymphocytes takes up residence in secondary lymphoid tissue (e.g. lymph glands, spleen, bone marrow) and divides to form two types of cells, memory cells, which are lymphocytes processed in the same way as themselves, and killer cells, which interact with the antigen. T-cell receptor sites sit on the surface of T cells and provide the specicity in antigen binding They have two components that give each dierent type a unique surface morphology and it is this that allows bonding to antigens.
This enhanced electron microscope picture shows a Killer T-cell (top right) about to attack a larger cancer cell.
T cell populations in the periphery
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