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Hematopoetic Stem Cells Rare: 1 in 10-50,000 cells in marrow; 1 in 100,000 in blood Relatively-rich in umbilical cord blood. Useful for stem cell transplants Join the National Marrow Donor registry!! http://bethematch.org/Home.aspx http://bethematch.org/Home.aspx
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How are HSCs identified? Functionally Colony formation assays Restoration of immune system Specific antigens on cell surface. Negative selection Positive selection
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Panning negative selection Lineage specific marker negative cells
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C-Kit = CD 117
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Aging marrow repleaced with fat (10% per year)
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http://www.youtube.com/watch?v=Z_mXDvZQ6dU
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Eosinophils attacking a schistosome larva in the presence of serum from an infected patient.
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(blood)
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(tissue)
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Common lymphocyte progenitor
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CD markers identified by 2 or more monoclonal antibodies (clusters of differentiation) Appendix 1.
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PART 2
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Flow Cytometry and Fluorescence Activated Cell Sorting (FACS)
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CD14 LPS receptor CD1a Lipid presentation to T cells
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Primary Lymphoid Organs fetal yolk sac fetal liver and spleen bone marrow thymus Secondary Lymphoid Organs lymph nodes spleen Peyer’s patches (M.A.L.T.)
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CD4 CD8
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nu/nu +/+ or +/nu
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antibody formation that requires CD4+ helper T cellsCD4helper T cells cell-mediated immune responses, which require CD4+ and/or CD8+ T cells cell-mediated immune responses delayed-type hypersensitivity responses (require CD4+ T cells)hypersensitivity killing of virus-infected or malignant cells (requires CD8+ cytotoxic T cells)malignantCD8cytotoxic T cells graft rejection (requires both CD4+ and CD8+ T cells) graft rejection and are furlesss Spontaneous deletion of FOXN1 gene (forkhead box protein N1) transcription factor Wikipedia hyperlinks Phenotype: nude mice are deficient in
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Secondary Lymphoid Organs Deployed in strategic locations to encounter infectious agents Location of adaptive immune response Clonal selection and expansion Differentiation into effector cells
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http://www.youtube.com/watch?v=pTSiuTQ1nwE
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Photomicrograph of Lymphatic vessel with valve 100x. Note the one way valve center of slide within the lymph vessel. Keeps flow of lymph going in one direction. There is a blood vessel running parallel to the lymph vessel.
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http://sss-hb.wikispaces.com/file/view/img00022.gif/77175863/img00022.gif
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Soluble, particulate or processed antigen enters pass through HEV
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periarterial lymphatic sheaths
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Something happens
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Downstream effects 1. Conformational change in receptor 2. Tyrosine kinase activation 3. Assembly of adaptor scaffold 4. Enzyme activation 5. Production of second messengers 6. Activation of transcription factor
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“Cyclosporin binds to the cytosolic protein cyclophilin (immunophilin) of lymphocytes, especially T cells. This complex of cyclosporin and cyclophilin inhibits calcineurin, which, under normal circumstances, is responsible for activating the transcription of interleukin 2. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NFATc), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines. Cyclosporin prevents the dephosphorylation of NFAT by binding to cyclophilin”.cyclophilinlymphocytesT cellscyclophilin calcineurininterleukin 2calmodulinNFATc Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye.
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metalloproteinases
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https://www.youtube.com/watch?v=HszzteDB5_M https:// www.youtube.com/watch?v=297HcgDxb7k
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