Introduction Lymphocyte development is complex and has several features including localization to primary lymphoid organs such as the bone marrow for B-cell development the thymus for T-cell development VDJ recombination in order to rearrange genetic material generate a unique B- or T-cell receptor positive selection in order to ensure all cells have functional receptors proliferation in order to expand the pool of potential lymphocytes allow for broad protection against different types of antigens negative selection in order to remove cells that target self-antigens protect against autoimmunity There are many mechanisms to increase diversity during lymphocyte development such as random recombination of genetic material during VDJ recombination random nucleotide addition to hypervariable regions by the protein TdT random assortment of different chains in receptor assembly heavy chains with light chains in B-cells alpha chains with beta chains in T-cells somatic hypermuation after antigen exposure only occurs in B-cells B-Cell Development B-cells develop in the bone marrow develop a unique B-cell receptor are tested to ensure that the receptor is functional are further tested for self-reactivity to prevent autoimmunity This development cycle is coordinated by the orderly progression through stages where supporting cells give feedback at every stage interaction strength of the B-cell receptor is monitored Stages of B-Cell Development Cell Type Developmental Steps Surface Receptor Associations Lymphoid stem cell Commitment to B-cell lineage None Pleuripotent Pro B-cell Heavy chain VDJ recombination Additional diversity from TdT modification Heavy chain only Recombination mediated by RAG proteins Defect in RAG leads to Omenn syndrome with no mature B cells Pre B-cell Allelic exclusion to ensure only one heavy chain expressed Positive selection Proliferation Pre B-cell receptor Key step in monitoring activity of the recombined heavy chain Immature B-cell Light chain VJ recombination Negative selection IgM receptor Inactivation of recombination machinery Key step in tolerance Mature B-cell Exit into blood stream IgM receptor IgD receptor Circulates and awaits activation by antigen T-Cell Development T-cells migrate from the bone marrow to the thymus where they develop a unique T-cell receptor are tested to ensure that the receptor is functional are further tested for self-reactivity to prevent autoimmunity This development cycle is coordinated by the orderly progression through stages where supporting cells give feedback at every stage receptors that bind too strongly lead to developing T-cell death the T-cell receptor undergoes selection in distinct compartments Stages of T-Cell Development Cell Type Developmental Steps Surface Proteins Associations T-cell precursor Commitment to T-cell lineage Migration to thymus None Lack of thymic development in DiGeorge syndrome Double negative Rearrangement of the β T-cell receptor chain Proliferation Pre T-cell receptor Occurs in the thymic cortex Double positive Rearrangement of the α T-cell receptor chain Expression of both CD4 and CD8 Positive selection against both class I and class II MHC CD4 CD8 T-cell receptor Occurs in the thymic cortex Key step in determining type of T-cell that develops MHC II binding leads to CD4+ cells MHC I binding leds to CD8+ cells Single positive Migration to medulla of thymus Negative selection against self antigens T-cell receptor Either CD4 or CD8 The transcription factor AIRE allows medullary cells to express proteins from all areas of body This ensure tolerance to vast majority of self antigens Mature T-cell Exit into blood stream Awaits peripheral activation T-cell receptor Either CD4 or CD8 Circulates and awaits activation by antigen
QUESTIONS 1 of 2 1 2 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.IM.13.74) A thymic sample from a fetus is examined. One cell type found was double-positive for the CD4 and CD8 receptors. What is the identity of these double-positive cells? Tested Concept QID: 100495 Type & Select Correct Answer 1 T-cell progenitors cells in the bone marrow 8% (7/90) 2 B-cells 0% (0/90) 3 Immature T-cells of the thymic cortex 77% (69/90) 4 Immature T-cells of the thymic medulla 13% (12/90) 5 Macrophages 2% (2/90) M 1 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review tested concept
All Videos (3) Login to View Community Videos Login to View Community Videos B Cell Overview Immunology - Lymphocyte Development and Structure D 2/16/2015 213 views 4.6 (5) Login to View Community Videos Login to View Community Videos T cell Development 2 of 2 Chris Robinson Immunology - Lymphocyte Development and Structure E 2/16/2015 58 views 0.0 (0) Login to View Community Videos Login to View Community Videos T cell Development 1 of 2 Immunology - Lymphocyte Development and Structure D 2/16/2015 87 views 4.0 (1)