8_ T-CELL ACTIVATION & EFFECTOR FUNCTION.pptx
Transcript
WELCOME! BMS 545 IMMUNOLOGY OCTOBER 4, 2024 OBJECTIVES (FROM LAST CLASS & TODAY) Define the immunological synapse & state its purpose Describe T-cell signal transduction and what signals are needed? Which activate? Which trigger anergy? Which trigger effector function? What are ITAMs...
WELCOME! BMS 545 IMMUNOLOGY OCTOBER 4, 2024 OBJECTIVES (FROM LAST CLASS & TODAY) Define the immunological synapse & state its purpose Describe T-cell signal transduction and what signals are needed? Which activate? Which trigger anergy? Which trigger effector function? What are ITAMs and what are their roles in the immunological synapse & signal transduction What is the importance & significance of IL-2? Compare & contrast CD4+ & CD8+ Maturation Identify the different sub-types of CD4+ cells, the roles of the five different subtypes we learned, and activation pathways (e.g. cytokines) that trigger the different responses (their effector functions) Define the different co-stimulatory molecules & signals (& back-ups) What is a memory T cell? Figure 8.11 Summary of the intracellular signaling pathways initiated by the T-cell receptor complex, the CD4 co-receptor, and the CD28 co-stimulatory receptor Just the start and finish is important. Appreciate the middle part exists, but I don’t expect you to know it. TCR SIGNALING https://digital.wwnorton.com/immunesystem5 (video is more in-depth than previous slides- the slides are fair game, the video is to help you visualize it) Activation of naive T cells by antigen 8-8 Antigen recognition in the absence of co-stimulation leads to a state of T-cell anergy Anergy- state of non-responsiveness to an antigen. T and B cells are said to be anergic when they cannot respond to their specific antigen Activation of naive T cells by antigen 8-7 Proliferation and differentiation of activated naive T cells are driven by the cytokine interleukin-2 (IL-2) Naive T cells & activated T cells express different forms of the IL-2 receptor **The alpha, beta, & gamma chains shown here NOT from the TCR or the TCR, they are their own receptor chains for IL-2** Figure 8.13 Proliferation and differentiation of activated T cells is driven by the cytokine interleukin-2 (IL-2) Activation of naive T cells by antigen 8-9 Activation of naive CD4 T cells gives rise to five types of effector CD4 T cell 8-10 The cytokine environment determines which differentiation pathway a naive T cell takes Figure 8.14 Five functional types of effector CD4 T cell are produced by activation and differentiation in different cytokine environments Yes, this is fair game, with the exception of the “defining transcription factor” he properties and functions of effector T cells 8-18 Effector TH1 CD4 cells induce macrophage activation TH1 CD4 cells activate macrophages to become highly microbicidal TH2 CD4 cells (not pictured) are an anti-inflammatory phenotype The properties and functions of effector T cells 8-19 Naive B cells and their helper TFH cells recognize different epitopes of the same antigen Activation of a naive B cell by a TFH cell 1. Naïve B cell binds antigen with BCR 2. Antigen is internalized by receptor-mediated endocytosis, processed, & presented via MHC II 3. Specific TFH cell forms cognate pair with B cell 4. Cognate interaction leads to expression of CD40L on TFH 5. CD40L on T cell interacts The properties and functions of effector T cells 8-20 Treg cells limit the activities of effector CD4 and CD8 T cells Autoreactive regulatory CD4 T cells (Treg) prevent the proliferation of autoreactive helper CD4 T cells Suppression of an autoreactive CD4 T cell by a Treg cell depends on both T cells interacting with the same antigen- presenting cell (APC), this allows cell-cell interactions & cytokines to affect in a Paracrine fashion (released to effect nearby cells) Activation of naive T cells by antigen 8-12 Naive CD8 T cells require stronger activation than that for naive CD4 T cells Figure 8.17 Two ways to activate a naive CD8 T cell Left- a naive CD8 T cell can be activated directly by a virus-infected dendritic cell Right- dendritic cell (or other virus- infected cell expressing MHC class II molecules) that induces insufficient co-stimulation can be helped by CD4 effector T cells to activate naive virus-specific CD8 T cell IL-2 secreted by CD4 T cell acts directly on naive CD8 T cell interacting with same dendritic cell & provides the necessary boost for activating CD8 T cell *Red rods & circles in dendritic cell represent viral proteins & their peptide degradation products Some CD8+ T cells lack CD28… CD58 is a back-up for co-stimulation (binds with CD2) The properties and functions of effector T cells 8-13 Cytotoxic CD8 T cells and effector CD4 TH1, TH2, and TH17 cells work at sites of infection Figure 8.19 Integrin VLA-4 enables effector T cells to home to inflamed tissue LFA-1 (integrin; adhesion molecule) binds to ICAMs & is expressed by all leukocytes LFA-1 contributes to T-cell interactions with a variety of types of target cell In addition to LFA-1, effector T cells express a second integrin, VLA-4, which binds to the VCAM-1 adhesion molecule VCAM-1 (vascular cell adhesion molecule; selectively expressed on the endothelium of blood vessels in inflamed tissue) recruits effector T cells from blood into infected tissue Figure 8.20 Co-stimulatory signals are required for activating naive T cells but NOT for activating effector T cells T CELL KILLING https://digital.wwnorton.com/immunesystem5 The properties and functions of effector T cells 8-14 Effector T-cell functions are mediated by cytokines and cytotoxins Figure 8.21 The effector molecules of cytotoxic CD8 T cells and helper CD4 T cells To know: perforin, granzymes, IFN-γ, IL-2, IL-4, IL-5, IL-10, TGF-β, IL-17, IL-21 (new- key role in B cell differentiation to plasma cells and in the development of T follicular helper cells, promoting functional germinal centers & immunoglobulin production) The properties and functions of effector T cells 8-16 Cytotoxic CD8 T cells are selective and serial killers of target cells at sites of infection T cell granule release: https://digital.wwnorton.com/immunesystem5 Figure 8.24 Cytotoxic CD8 T cells can kill several infected target cells in succession The properties and functions of effector T cells 8-17 Cytotoxic T cells kill their target cells by inducing apoptosis MEMORY T-CELLS Some CD4+ T cells enter a memory state Memory T cells typically express CD28, increase their expression of some adhesion molecules but decrease their surface expression of L-selectin By increasing their expression of CD28, memory T cells are more likely to respond rapidly to CD80/86 displayed by APC By decreasing L-selectin expression, memory T cells no longer home to lymph nodes but home to sites of inflammation because of increased expression of other adhesion molecules MEMORY T CELLS CD8+ T cells can also form memory cells (not shown) CD58 is increased in memory connections
