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Antigen Processing and Presentation

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Topic updated on 04/02/16 11:10am

Overview
  • Antigens are processed two ways
    • endogenous
    • exogenous
  • Antigens are presented to two distinct cell populations
    • CD4+ T-cells
    • CD8+ T-cells
  • The processing pathway determines the presentation pathway
Antigen Processing
  • Endogenous
    • presentation via class I MHC to CD8+ T lymphocytes
    • presents proteins found in cell
      • e.g., viral proteins
    • mechanism
      • degradation of protein
      • peptides transported from cytosol into ER via TAP complex
      • combine with newly made class I MHC in ER
      • transport to cell surface for presentation
    • MHC class I deficiency
      • mutation in TAP 1 molecule
        • cannot transport peptides into ER for loading onto MHC I
      • absent CD8+
        • recurring viral infections
        • can control some viral infections with NK cells
      • normal CD4+ counts
        • often overproduce antibodies without negative feedback from CD8+
  • Endosomal (exogenous)
    • presentation via class II MHC to CD4+ T lymphocytes  
    • presents antigens phagocytosed from exterior
      • e.g., bacteria
    • mechanism
      • phagosome digested
      • fusion of phagosome with endosome containing newly synthesized class II MHC
        • class II MHC has antigen binding site covered with invariant chain to prevent "self-presentation"
      • invariant chain degraded and antigen is loaded
      • transport to cell surface for presentation
    • occurs in all antigen presenting cells (APCs)
      • dendritic cells (major)
        • langerhans cells
      • macrophage/monocytes
      • B-cells
    • takes place during transition from surveillance area to secondary lymph organ
    • MHC class II deficiency
      • aka. Bare lymphocyte syndrome type II
      • mimics mild form of SCID
        • main difference that lymphocytes do respond to mitogens
      • do not develop graft-versus-host rejection
        • MHC II required
      • CD4+ deficiency
      • reduced numbers of CD8+
        • results from lack of Th1 cytokines for proliferation
      • moderate hypogammaglobulinemia
Antigen Presentation
  • MHC II/CD4+ model
    • APCs contact naive T cells in secondary lymph organ
  • Process
    • initial binding
      • binding of class II MHC with T-cell receptor
        • stabilized by CD4+ of T-cell
        • super antigens can non-specifically link these binding molecules
          • results in polyclonal T-cell activation and ↑↑↑ INF-γ
            • toxic-shock syndrome toxin-1 (TSST1)
            • streptococcal pyrogenic exotoxin
            • staphylococcal exterotoxins
    • further binding
      • integrins of T-cell bind ICAMs of APC
      • ICAMs of T-cell bind integrins of APC
        • both increase cell-to-cell adherence
        • similar to the firm adhesion of rolling neutrophil with an endothelial cell
      • CD28 of T-cell bind B7 protein of APC
    • cytokine signaling
      • APC stimulates T-cell
        • IL-1
        • IL-6
        • TNF-α
      • T-cell stimulates APC
        • IFN-γ
      • T-cell stimulates itself
        • IL-2
  • Activated cell fate
    • T-cell now a helper T-cell and undergoes clonal expansion
      • can choose 1 of 4 helper T-cell types
      • decision based on
        • amount of antigen stimulus
        • genetic factors
  • MHC I/CD8+ model
    • see cell mediated immunity for details

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Qbank (1 Questions)

TAG
(M1.IM.24) Antigen presentation of extracellular pathogens by antigen presenting cells requires endocytosis of the antigen, followed by the degradation in the acidic environment of the formed phagolysosome. Should the phagolysosome become unable to lower its pH, what is the most likely consequence? Topic Review Topic

1. Deficient NK cell activation
2. Deficient presentation of pathogens to CD4 T-cells
3. Deficient presentation of pathogens to CD8 T-cells
4. Deficient cell extravasation
5. Deficient expression of B7

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