Ch 5 T Cell-Mediated Immunity Flashcards
What are the components of the TCR complex? Which of these components are responsible for antigen recognition and which for signal transduction?
The T cell receptor (TCR) complex is made up of the TCR α and β chains responsible for antigen recognition and the CD3 complex and ζ homodimers required for signal transduction.
What are some of the molecules in addition to the TCR that T cells use to initiate their responses to antigens, and what are the functions of these molecules?
Molecules other than the TCR used by T cells to respond to antigens include the CD4 and CD8 co-receptors, which bind to class II and class I MHC molecules, respectively; costimulatory receptors such as CD28, which bind to costimulators expressed on activated APCs; and adhesion molecules such as the integrin LFA-1, which mediate cell-cell adhesion and control the migration of the T cells.
What is costimulation? What is the physiologic significance of costimulation? What are some of the ligand-receptor pairs involved in costimulation?
Costimulation refers to signals delivered to a lymphocyte that are required for lymphocyte activation but are independent of antigen receptor signaling. Costimulatory signals are commonly referred to as a “second signal” and provide lymphocytes with the information that the antigen they are recognizing may be of microbial origin. B7-1 and B7-2 are the major costimulators on antigens presenting cells that bind to CD28 on T cells.
Summarize the links among antigen recognition, the major biochemical signaling pathways in T cells, and the production of transcription factors.
Antigen recognition results in co-receptors in T cells bringing the Lck tyrosine kinase in proximity to CD3 and ζ chain ITAMs. Phosphorylation of the ITAMs results in the recruitment and activation of ZAP-70 tyrosine kinase, which in turn initiates different signaling pathways by activating different downstream enzymes. Activation of phospholipase Cγ results in the calcium signaling and the subsequent activation of the NFAT transcription factor. Activation of PKCθ results in the activation of the NF-κB transcription factor. Activation of MAP kinases leads to the production of the AP-1 transcription factor.
What is the principal growth factor for T cells? Why do antigen-specific T cells expand more than other (bystander) T cells on exposure to an antigen?
The major growth factor for T cells is interleukin-2 (IL-2). Antigen-specific T cells receive antigen receptor signals, costimulation and cytokine-mediated stimulation. T cells that have recognized antigens express increased levels of receptors for growth factors and are thus preferentially stimulated during immune responses to the antigens.
What are the major subsets of CD4+ helper T cells, and how do they differ?
CD4+ helper T cell subsets include TH1 cells that produce interferon-γ, which stimulates the microbicidal activities of phagocytes. TH2 cells secrete IL-4, IL-5, and IL-13 and mediate allergic and antihelminthic responses. TH17 cells make IL-17 and contribute to neutrophil recruitment to sites of infection.
What signals are required to induce the responses of CD8+ T cells?
CD8+ T cells are activated by peptide–class I MHC antigens, costimulatory signals, and cytokines (e.g., IL-12) and differentiate into cytotoxic T cells.
