Cellular Immune Response II PDF

Cellular Immune Response II Differentiation and Functions + of CD4 Effector T Cells Felix N. Toka DVM, PhD, DSc. Professor Veterinary Virology & Immunology Department of Biomedical Sciences Objectives Define the key functional subsets of CD4+ T cells Emphasize the cytokine production by CD4+ T cells...

Cellular Immune Response II Differentiation and Functions + of CD4 Effector T Cells Felix N. Toka DVM, PhD, DSc. Professor Veterinary Virology & Immunology Department of Biomedical Sciences Objectives Define the key functional subsets of CD4+ T cells Emphasize the cytokine production by CD4+ T cells Define the role of each CD4+ T cell subset Role of CD4+ T cells in eradicating infections CD4+ T cell responses involve: initial activation in lymphoid organs generation of effector and memory cells migration of effector cells to sites of infection elimination of infectious pathogens at these sites Reactions of CD4+ T cells in cell-mediated immunity Functions of CD4+ T cells are mediated mainly by cytokines CD4+ effector T cells are classified according to the cytokines they produce Subsets of CD4+ Effector T Cells Three major subsets of CD4+ effector T cells TH1, TH2, TH17 follicular helper T cells Naïve CD4+ T cells APC Development of TH1, TH2, and TH17 Subsets TH1, TH2, and TH17 cells all develop from naive CD4+ T lymphocytes The development process is sometimes referred to as polarization of T cells The process can be divided into induction stable commitment amplification The TH1 Subset The TH1 subset is: induced by microbes that are ingested by phagocytes induced by microbes that activate phagocytes the major effector T cell population in phagocyte-mediated host defense, the central reaction of cell-mediated immunity Development of TH1 Cells TH1 differentiate in the presence of IL-12 and IFN-γ produced by dendritic cells, macrophages, and NK cells IFN-γ and IL-12 stimulate TH1 differentiation by activating the transcription factors T-bet, STAT1, and STAT4 Development of TH1 cells Functions of TH1 Cells The principal function of TH1 cells is to activate macrophages to ingest and destroy microbes TH1, or follicular helper T cells stimulate the production of some IgG antibodies Effector functions of TH1 cells are mediated through IFN-γ Functions of TH1 cells. Why is IFN-γ so important for TH1 cells? (also called type II interferon) IFN-γ activates macrophages to kill phagocytosed microbes IFN-γ acts on B cells to promote IgG2a subclass switching and inhibits switching to IgE IFN-γ amplifies the TH1 subset and inhibits the development of TH2 and TH17 cells IFN-γ stimulates expression of molecules that enhance antigen presentation (e.g., MHC I and II) Therapeutic use of IFN-γ in veterinary medicine Recombinant canine IFN-γ (KT-100) in atopic dermatitis hIFN-γ against canine astrocytoma - clinical trials, gene therapy fIFN-γ in combination with fIL-2 and fGM-CSF – clinical trials fibrosarcoma, gene therapy IFN-γ gene therapy in canine brain tumors TH1-Mediated Classical Macrophage Activation and Killing of Phagocytosed Microbes TH1 cells activate macrophages by contact-mediated signals delivered by CD40L-CD40 interactions and by IFN-γ The TH2 Subset The TH2 subset mediates phagocyte-independent defense Eosinophils and mast cells play central roles in this defense. Important for the eradication of helminthic infections Central to the development of allergic diseases Development of TH2 Cells TH2 differentiation is stimulated by IL-4 in response to helminths and allergens IL-4, IL-5 and IL-13 are the main TH2 cytokines http://www.dailymail.co.uk/sciencetech/article2957265/When-white-blood-cells-ATTACK-Amazing-videocaptures-moment-immune-takes-parasitic-worm.html Development of TH2 cells Functions of TH2 Cells TH2 cells stimulate: production of IgE mast cells eosinophils, these reactions eliminate helminthic infections alternative macrophage activation Functions of TH2 cells Classical and alternative macrophage activation The TH17 Subset The TH17 subset is responsible for recruiting leukocytes and inducing inflammation critical for destroying extracellular bacteria and fungi contribute to inflammatory diseases Development of TH17 Cells TH17 cells are stimulated by pro-inflammatory cytokines produced in response to bacteria and fungi IL-1 and IL-6 initiate TH17 differentiation IL-23 maintains proliferation and differentiation of TH17 cells Functions of TH17 Cells TH17 cells combat microbes by recruiting neutrophils to sites of infection They produce IL-17 which induces neutrophil-rich inflammation IL-17 stimulates the production of antimicrobial substances