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Lymphocyte Development and Structure

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Topic updated on 12/01/16 8:07am

Overview
  • LymphocThis illustration highlights the basic development of various blood cells from hematopoietic stem cells.yte development takes place in primary lymphoid organs
  • 4 mechanisms for generation antigenic recognition diversity during lymphocyte development via
    • VDJ recombination
    • random chain combination
    • nucleotide addition via Tdt
    • somatic hypermuation 
      • only B-cells
B-Cell Development
  • Bone marrow stages
    • lymphoid stem cell
    • pro-B cell
      • begins expression of differentiated membrane markers
        • CD19
        • CD20
        • CD21
        • CD40
        • MHC II
      • B-cell receptor (Ig) gene undergoes Ig heavy chain rearrangement in DNA
        • mediated by rag (recombination activating genes)
        • D-J recombination first
        • V-DJ recombination second
        • VDJ-C recombination last
        • Omenn syndrome
          • missense mutation in rag gene resulting in partial activity
          • no mature B-cells
          • marked decrease in T-cells
      • during heavy chain rearrangement terminal deoxyribonucleotidyl transferase (Tdt) randomly inserts bases at VDJ junctions
        • increases diversity
      • once successful other homologous gene copy shut off
        • allelic exclusion
    • pre-B cell
      • undergoes Ig light chain rearrangement in DNA
      • mediated by rag (recombination activating genes)
      • V-J recombination first
      • VJ-C recombination second
        • no D domain in light chain
      • Tdt is shut off after heavy chain rearrangement so no base insertion in light chain
      • cytoplasmic μ+
    • immature/naive B-cell
      • leaves bone marrow
        • if the Ig has too much similarity to self it cannot leave
          • clonal deletion
          • generate tolerance to self
      • now IgM+
  • Periphery stages
    • circulate to secondary lymphoid organs
    • if activating antigen is encountered
      • forms a germinal center in lymph organ
      • rapid clonal expansion
        • blast B-cell
      • undergoes somatic hypermutation
        • random point mutations of variable region
        • mediated by activation-induced deaminase (AID)
        • fine tuning idiotype to make a stronger binding affinity
          • known as affinity maturation
      • if self is detected in the periphery cell undergoes clonal anergy
      • isotype switching to IgG,E, or A
      • now a mature plasma cell or memory B-cell
T-cell development   
  • Prethymic stage (bone marrow)   
    • lymphoid stem cell
    • migrates from bone marrow to thymus
  • Thymic cortex stage 
    • undergoes α and β chain rearrangement in DNA
    • mediated by rag
      • D-J recombination first
      • V-DJ recombination second
      • VDJ-C recombination last
    • during rearrangement Tdt is active
      • adds to diversity
    • undergoes allelic exclusion following successful rearrangement
    • positive selection occurs in the cortex
      • binding moderately strong receives positive selection
      • 1 out of 100 cells is successful
    • begins expression of
      • CD2
      • CD3
      • TCR
      • CD4 AND 8
  • Thymic medulla stage 
    • developing T-cells pass into medulla where it encounters presentations of self by certain cell types
      • cortical epithelial cells
      • dendritic cells
    • negative selection occurs in the medulla
      • binding too strongly receive negative selection and apoptosis induced 
      • binding too weakly receives neither positive or negative selection
    • binding to either MHC I or II determines development as CD8+ or CD4+
      • other non-binding CD4 or 8 is shut off
    • leaves thymus as naive CD8+ or CD4+ T-cell
  • Peripheral stages
    • homes to secondary lymphoid organs where it awaits activation
    • see T-cell activation


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Qbank (1 Questions)

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(M1.IM.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? Topic Review Topic

1. T-cell progenitors cells in the bone marrow
2. B-cells
3. Immature T-cells of the thymic cortex
4. Immature T-cells of the thymic medulla
5. Macrophages

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