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Lecture 21: "Immunogenetics"

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Biology 1002B
Tom Haffie

Biology Lecture No. 21: Immunogenetics th Monday March 26 , 2012 RECALL: -A vast amount of radiation received is a natural part of the environment. DNA suffers reactive oxygen as a result of ionizing radiation all the time. About 10% of total exposure derives from X-Rays. -Down Syndrome incidence spiked in Belarus 9 months after Chernobyl and there is also an increase in thyroid cancer in children. Reactive oxygen can cause breaks in DNA helix, resulting in chromosomal rearrangements. -Chromosomal rearrangements are attempts to repair damage to DNA. It is impossible to detect substitutions that are wrong; one cannot simply fix mutations. The Mechanisms Leading To Burkitt Lymphoma: -The J’s, D’s and V’s are antibody producing sequences of the antibody genes on chromosome 14. Antibody genes have two enhancers and very powerful expression machinery because when antibodies are needed, they are desirable in great abundance. -The translocation of chromosome 8 and 14 puts the oncogene C-Myc under the control of these antibody genes. When an oncogene is put under the control of powerful promoters, it is not surprising that cancer (lymphoma) results. The Origin Of Blood & Lymph Cells: -All blood cells and immune system cells derive from pluripotent hematopoietic stem cells. B lymphocytes, T lymphocytes and Natural killer (NK) cells are the products of lymphoid stem cell maturation. The maturation of B cells (important in immunology) is where the action of making antibody genes occurs. Innate Immune System: -There are two types of immune responses in humans: innate and adaptive. The innate immune system is shared with other life-forms such as invertebrates and plants and is non-specific (it defends against all possible threats to the body. -This response protects by devouring bacteria and other foreign antigens whole by way of phagocytosis. Cytokines and chemokines are chemical messenger proteins that are used by the immune cells to communicate with each other and to attract other cells to the scene of injury. -The amine histamine is used to increase the permeability of capillaries, allowing immune cells to get out of blood cells to the site of injury. -There are no antibodies involved in the innate immune response; it is solely cell-based and histamine- based. The innate immune system is not capable of possessing any memory. Adaptive Immune System: -The portion of the immune system that involves mutation is known as the adaptive immune system. The adaptive immune system is specific and it has a memory capable of remembering past exposures to foreign biological threats. -The adaptive immune response can be divided into two subcategories: cell-based (where cells are eliminating pathogens) and antibody-based (where antibodies are eliminating pathogens). -Lysosomes proteasomes are responsible for the breakdown of substances. These fragments (antigens) of a particular virus are displayed on the surface of the infected cell. T-cells have receptors that recognize these particular antigens, which then stimulate those T-cells to divide. When T-cells become activated, they divide uncontrollably. Cell-Based Elimination Of Infected Cells: -After activation, T-cells go off in pursuit of other infected cells and eliminate them. This action represents the cell-mediated arm of the adaptive immune response. -A method by which killer T-cells eradicate infected cell is through the secretion of proteins known as perforins, which puncture the infected cell and ultimately induce death through leakage of cellular fluids and material. Antibody-Based Elimination Of Infected Cells: -Even though cells are involved in this process, it is ultimately the antibodies that are facilitating elimination. a) Dendritic Cells & The Formation Of The APC: -Dendritic cells are highly mobile, patrolling the body, searching for non-self cells. Once they’ve spotted an invading cell or virus, the dendritic cell performs phagocytosis and displays the foreigner’s many different specific antigens on the surface of its cell membrane. After this has been accomplished, the dendritic cell is known as an antigen-presenting cell (APC). b) The APC & The Activation Of Helper T-Cells: -The APC is then ready to travel to the lymph nodes where it confirms these viral antigens to T-4 cells. Each of these T-cells is different as their receptors are specific to a particular antigen presented by the APC. Only the proper T-cell receptor will bind to the antigen presented. -Once bound, the APC will secrete the chemical messenger interleukin (protein), which activates the T- cell. Cell division is stimulated from activated T-cells secreting cytokines. Instead of seeking biological threats, these T-cells (Helper T-cells) set out to find B-cells. c) Helper T-Cells & B-Cell Production: -Every Helper T-cell is responsible for aiding B-cells in
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