Thursday, February 28, 2008

Immunity - Lymphocytes

Lymphocytes: these are the cells that are responsible for specific immune responses. There are two distinct classes of lymphocytes:

B lymphocytes: are the cells that produce antibodies. The specific antigen receptors on B cells are membrane-bound forms of antibodies. Antibody producing B cells are called plasma cells.

T lymphocytes: do not produce antibody molecules. They produce a wide variety of molecules called cytokines that mediate immune resistance and have the capacity to directly kill other cells. There are at least three main types of T cells:

Helper T lymphocytes: (CD4+) participate in th activation and development of B lymphocytes, the activation of macrophages and the inflammatory response. They recognize foreign antigens presented by cells displaying MHC Class II molecules. You can see an animation of how this works here.

Helper T lymphocytes can be further divided into TH1 and TH2 lymphocytes.

Pathways to TH1 and TH2 lymphocyte differentiation can be seen here.

TH1 and TH2 lymphocytes are differentiated by the cytokines that they secrete. Cytokines are small protein hormones that mediate and regulate immune responses and inflammation. Learn more about cytokines here, here and here.

Cytotoxic T lymphocytes: (CD8+) are the cells that have the capacity to kill virus-infected cells, tumor cells and allografts. They can also mediated other forms of cell-mediated immunity. They recognize foreign antigens presented by cells displaying MHC Class I molecules.

Regulatory T lymphocytes: (FoxP3+) are T cells that act to suppress or regulate the activation of the immune system. These cells are probably important in preventing the expression of autoimmune diseases. These cells are a relatively recent discovery and it is not yet known exactly how they work in many cases.

Lymphocytes can also be differentiated based on the surface proteins they express called clusters of differentiation.

Here is a pretty good representation of the overall immune response to a viral infection obtained from a U. of Texas website.

Down the left side of the picture:

1) A host cell becomes infected with a virus.
2) The cell processes and presents viral antigen epitopes bound to MHC Class I molecules to the antigen receptor on a CD8+ cytotoxic T cell.
3) Activated effector viral antigen-specific CD8+ cytotoxic T cell recognizes a virally infected cell and kills it.
4) After viral pathogen is cleared some CD8+ viral specific cytotoxic T cells become memory cells.

Down the right side of the picture:

1) Lysed virally infected cell releases viral particles.
2) Viral particles are engulfed by activated macrophages, processed and presented, bound to MHC Class II molecules, to the CD4+ helper T cells.
3) CD4+ helper T cell becomes activated, proliferates, differentiates and secretes cytokines to help B cells become antibody producing plasma cells and CD8+ cytotoxic cells to become better killers.
4) Later in the response, viral specific B lymphocytes become very potent antigen presenting cells due to their antigen receptors.
5) As virus is cleared, CD4+ T cells and B cells become either die or become memory cells.

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