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T-cell Activation

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Topic updated on 03/31/16 12:20am

Antigen presentation
  • APCs present to T-cell receptors (TCRs) 
    • TCR specific for the presented antigen
    • either to CD8+ or CD4+
      • determines response        
MHC II/CD4+ model
  • APCs interact with naive T cells in secondary lymph organ
    • three signals required for T-cell activation
      • initial binding
        • binding of class II MHC with T-cell receptor  
          • stablized by CD4+ of T-cell 
          • super antigens can link constant regions of these binding molecules
      • costimulation
        • integrins of T-cell bind ICAMs of APC
        • ICAMs of T-cell bind integrins of APC
          • both increase cell-to-cell adherance
          • similiar 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 via
          • IL-1
            • also stimulates growth B cells, neutrophils, fibroblasts, and epithelial cells
          • IL-6
            • also secreted by Th cells
            • increases production of Igs
            • increases production of acute phase reactants
              • mannose-binding lectin
              • C-reactive protein
              • fibrinogen
          • TNF-α
        • T-cell stimulates APC
          • INF-γ
        • T-cell stimulates itself
          • IL-2
  • 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
  • Three step activation
    • loose attachment
      • non-specific interaction between LFA-1 integrin with ICAM-1
    • recognition (firm attachment)
      • T-cell receptor (TCR) + class I MHC
      • must recognize and bind to self MHC as well as bind antigen
      • recognizes non-self class I MHC during non-genotypically indentical human transplants due to polymorphisms in structure between individuals
    • acitviation from TH1 cells
      • via IL-2
  • Amplification
    • can replicate autonomously
      • slow and does not reach high cell concentrations
    • TH1 cells can enhance CTL division
      • via IL-2

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(M1.IM.77) A 25-year-old woman presents to the ED with a diffuse, erythematous rash in the setting of nausea, vomiting, and fever for 2 days. Physical exam reveals a soaked tampon in her vagina. Blood cultures are negative. The likely cause of this patient's disease binds to which molecule on T cells? Topic Review Topic

1. CD3
2. Gamma chain of the IL-2 receptor
3. CD40 ligand
4. Variable beta portion of the T-cell receptor
5. Fas ligand

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