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Genetics of Antibodies. Oct 18, 2005. Antibody Structure. Primary Immune Response (note: differentiated cells). (lymphocytes) come from the bone marrow (lymphocytes) come from the thymus ( esp . macrophages ) initiate the immune response. Antigenic Differentiation.
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Genetics of Antibodies Oct 18, 2005
Primary Immune Response(note: differentiated cells) • (lymphocytes) come from the bone marrow • (lymphocytes) come from the thymus • (esp. macrophages) initiate the immune response
Antigenic Differentiation • B lymphocytes become plasma cells and Memory B cells • T lymphocytes become: Killer T cells Helper T cells Suppressor T cells Memory T cells
Secondary Immune Response • When a second dose of antigen is presented to the system the response is much larger than with the first dose (super differentiation). • Memory B lymphocytes divide and produce many specific antibody producing plasma cells. • Memory T cells divide and produce many killer T cells.
Secondary Response • Only the memory cells that make an antibody that is specific to the antigen are stimulated to divide. • For any one antigen this may be 20 to 30 different memory B cells or memory T cells. Each one produces a different antibody, but all can bind to the antigen.
G1– Somatic Recombination in the formation of antibody genes in “super differentiated” antigenic state • Between the gene segments to be joined (such as the V and J segments) there are sequences that form stem loop intermediates so as to bring the joining segments into proximity. • Recombination then takes place between appropriate points of the two segments.
Somatic Recombination within a single chromatid (G1) Recombination can occur over very long distances because the DNA is arranged in a series of spirals, thus bringing widely spaced recombination sites together.
The Joining Step • The J-exons create an unpredictable union between the V-exon and the C-exon • The connection becomes a single amino acid, and is not a "typical" exon • A mistake becomes a frame shift mutation, and causes the locus to be inactivated • Only one locus of a kind functions in a given cell --> "allelic exclusion"
dsDNA 100+ options Processing Step, eliminating intervening DNA
Berkitt’s Lymphoma • When the viral promoter controls the fos proto-oncogene, uncontrolled cell proliferation occurs…..Berkitt’s lymphoma.