BMS 545 Immunology Lecture Notes PDF

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