Immunology 4 - Immunology 4-Central and Peripheral Lymphoid...

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Immunology 4-Central and Peripheral Lymphoid Organs Central Lymphoid Tissues: Major roles Lymphoid immune cells undergo final stages of development in central (primary) lymphoid tissue= where rearrangement of receptors occurs; T-cells: bone marrow→ thymus; B cells: bone marrow Lymphopoiesis, starting in bone marrow Antibody/TCR gene rearrangement T-cell education→ restricts T-cells to MHC I or MHC II Central tolerance—get rid autoreactive cells Bone Marrow Site of hematopoiesis Site where B-cells rearrange their antibody genes and undergo central tolerance T cells start in bone marrow but migrate to thymus for final development Immune cells develop in CAVITIES between bony trabeculae Areas of hemoatopoietic marrow in the spaces between bony trabeculae Some space is occupied by adipocyte= more prominent as you age Central Tolerance: B cells B-cells with antibodies that recognize self antigens: →die through apoptosis OR try to edit antibody to remove autoreactivity Some antibody remains on B-cell=acts as a signalling receptor to trigger intracellular pathways Bone Marrow and B-cell Central Tolerance Reticular cell=make type III collagen (reticular tissue)—supportive, and growth factors (support development) Self antigens= source unknown, may be on reticular or stromal cells Stromal cells= make connective tissue and growth factors; may or may not present self antigens to B-cells Osteoblasts=deposit new bone Blood vessels= where mature(naive) cells exit Thymus Sits on top of heart Many mini compartments surrounded by capsule 2 regions: 1. Cortex= dense= T-cells in earliest stage of development, support rearrangement, have macrophages to take up autoreactive cells 2. Medulla=less cellular (less dense)= mature T-cells Site where T cells complete development after release from bone marrow Rearrange TCR gene→ checks for successful rearrangement= positive selection Undergo central tolerance→ removal of auto-reactive cells=negative selection Thymus and T-cell Development “Nude” mouse= equivalent genetic disorder extremely rare in humans (6 known)= no hair or thymus Mutation in FOXN1 gene=expressed in skin and thymus (epithelial cells)=required for terminal differentiation of some types of epithelium Highly susceptible to infection→ no T cells Grafting thymus into nude mouse restored development→ everything before thymus stage is fine; everything after doesn’t function Thymus Defects in Humans DiGeorge Syndrome 22q11.2 deletion
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Rare (1:4000) Underdeveloped thymus=smaller than normal but not completely gone: small number of T cells, susceptible to viral, fungal and opportunistic infections, high risk of autoimmunity in older children (decreased negative selection because decreased functioning thymus) ex arthritis→ fungal and opportunistic infections usually don’t affect us but will if decreased T-cells
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This note was uploaded on 02/08/2012 for the course PATHOLOGY 3245 taught by Professor X during the Spring '11 term at UWO.

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Immunology 4 - Immunology 4-Central and Peripheral Lymphoid...

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