10_Activation_of_the_nave_T_cell_Szalai2023.pptx

Activation of the naïve T cell Molecules to People Course 2023 Dr. Gabor Szalai Email: [email protected] Objectives Overview of Lymphocyte activation Direct contact and Cytokines DC, macrophage via Cytokines Target cell They present identical peptide on MHC II to the TH They present ident...

Activation of the naïve T cell Molecules to People Course 2023 Dr. Gabor Szalai Email: [email protected] Objectives Overview of Lymphocyte activation Direct contact and Cytokines DC, macrophage via Cytokines Target cell They present identical peptide on MHC II to the TH They present identical peptide on MHC I to the CD8+ T cell CD8+ T cell activation and function Intimidation is achieved by: Mak, Tak W., Primer to The Immune Response Copyright © 2014 Copyright © 2014 Elsevier Inc. All rights reserved • Release of oxidative enzymes into target cell • Perforins - made by the CTL, makes pores on the surface of target cells • Other soluble factors - such as TNF • FasL Target cell dies by apoptosis. Naïve Th cell activation Interactions: CD4 * MHC II: docking pMHC II * TCR B7 * CD28: ligand-receptor type CD40 * CD40: ligand-receptor type Immunological synapse Mak, Tak W., Primer to The Immune Response Copyright © 2014 Copyright © 2014 Elsevier Inc. All rights reserved The activated Th (a.k.a Th0 cell) will become an effector cell (Th1, Th2, Th17) based on cytokine signal (see later). B cell activation ssume Th0 received IL4 signaling and became Th2 cell Identical peptide Mak, Tak W., Primer to The Immune Response Copyright © 2014 Copyright © 2014 Elsevier Inc. All rights reserved T cell subsets Major T-Cell Functions: • Helper (CD3+, CD4+) function Cytokine production & cell-to-cell contact for activation • Regulatory (CD3+, CD4+) function Cytokine production & cell-to-cell contact for suppression • Cytotoxic (CD3+, CD8+) function  Cell-to-cell contact for destruction The BIG PICTURE Th cell subsets Mak, Tak W., Primer to The Immune Response Copyright © 2014 Copyright © 2014 Elsevier Inc. All rights reserved Th cell subsets The information about the transcription factors is FYI only (not on the exam) This is one example of how cells of the innate and adaptive immune responses cooperate. Dendritic cells (DC) recognize microbes via various receptors including pattern-recognition receptors (PRR). They take up antigen and present peptides to T cells for recognition. Signals from the DC help determine which Tcell subsets emerge. Basic Immunology: Functions and Disorders of the Immune System, 4th Ed., Abbas, Abul K., MBBS, Copyright © 2014 by Saunders, an imprint of Elsevier Inc. Abbas: Basic Immunology, 4th ed. Copyright © 2012 Saunders, An Imprint of Elsevier The fate of mature T cells Mature T cells circulate, and spend time in the secondary lymphoid organs and tissues. There they may encounter their specific antigen, receive appropriate accessory signals, proliferate and differentiate into effector or memory cells. These cells then go to peripheral tissues to carry out their function. Unspecific lymphocyte Polyclonal mitogens - trigger ALL (T or B) lymphocytes to activation undergo blast transformation and cause resting cells to divide, generally you don’t want this to happen Examples 1.Plant Lectins - they bind to polysaccharides  Concanavalin A - (con A) binds to T cells and triggers blast transformation. Comes from jack beans  Phytohemmaglutinin - binds to T cells and triggers blast transformation. Comes from kidney beans 2.Pokeweed mitogen - causes both T and B cells to undergo blast transformation 3.αIgM - acts on B cells  has to be divalent or more to cross-link 4.Lipopolysaccharides - (LPS) act on B cells 5.Bacterial toxins - some that are found in spoiled Superantigens A superantigen is a molecule derived from microbial organisms that stimulate lymphocytes by binding to the TCR, outside of the antigen-binding site (but still the variable region) or to the MHC II molecule. Example: Staphylococcal protein enterotoxin B (SEB or SE) • Binds to a part of the TCR-β chain coded by the TCR Vβ, a region shared by many T cells (20% of all T cells) causing cytokine overproduction. • Binds directly to MHC II on the surface of antigen presenting cells (APC) and NOT processed by the (ingest-digest-display) by the APC Oher example: Toxic shock syndrome toxin (TSST) produced by produced by 5 to 25% of Staphylococcus aureus isolates The BIG PICTURE Thank you for your attention!