TBL Integration I Cytokines and soluble molecules.pdf

Cytokines General features of cytokines mediating innate and adaptive immunity Feature Innate immunity Adaptive immunity Example TNF-a, IL-1, IL-12, IFN-g* IL-2, IL-4, IFN-g* Main source DC, Macrophages, NK cells T cells Main functions Mediators of innate immunity and inflammation Ad...

Cytokines General features of cytokines mediating innate and adaptive immunity Feature Innate immunity Adaptive immunity Example TNF-a, IL-1, IL-12, IFN-g* IL-2, IL-4, IFN-g* Main source DC, Macrophages, NK cells T cells Main functions Mediators of innate immunity and inflammation Adaptive immunity: lymphocyte differentiation and growth, activation of effectors (macroph, eosinoph, mast cells) Stimuli Bacterial LPS, Viral nucleic acids Protein antigens Amounts May reach elevated levels, detectable in serum Usually low, undetectable in serum Local/systemic effects Both Local Associated diseases Systemic diseases (e.g. septic shock) Local lesions (e.g. granulomatous inflammation) Inhibitors Corticoids Cyclosporin, FK-506 Cytokine receptors • Expression of receptors determines cell sensitivity to cytokine signals. • Different types of cytokine receptors grouped according to: Ø Type of molecule (structure of the protein chain and domains) Ø Protein subunits constituting a multi-chain receptor. Cytokine receptors • Expression of receptors determines cell sensitivity to cytokine signals. • Different types of cytokine receptors grouped according to: Ø Type of molecule (structure of the protein chain and domains) Ø Protein subunits constituting a multi-chain receptor. Specificity Signaling TNF-a • Main mediator of acute inflammatory responses against gram (-) bacteria and infections, induced by LPS • Produced by: activated macrophages, T cells • Two receptors: TNF-RI (p55) and TNF-RII (p75) with low affinity Kd~10-9-10-10 • Responsible for systemic complications in infections Local infection Neutrophil and monocyte activation Systemic infection Systemic clinical and anatomopathological abnormalities IL-12 • Main mediator of innate immunity against intracellular pathogens: activation of Th1 cells • Heterodimer (p35 and p40 chains) • Produced by macrophages and DC in response to PAMPs, CD40L or IFN-g. • Stimulates synthesis of IFN-g by NK cells and T cells and cytolytic activity Type I IFNs • Mediate early innate antiviral immune responses • Two main groups: members) and IFN-b. • Produced by leukocytes (plasmacytoid DC) and by many other cells, respectively. • Main stimulus is viral (ssRNA, dsRNA, DNA) • Upregulates MHC-I expression • Immunostimulatory properties IFN-a (~20 infection Interleukin 2 • T cell growth factor: clonal expansion after Ag recognition • Produced mainly by CD4 and also by CD8 T cells • Ag encounter upregulates IL-2R expression • Induces proliferation of other cells: NK, B cells Interferon gamma (IFN-g) • Homodimer produced by NK, Th1 CD4+ and CD8+ T cells. • Main cytokine mediating macrophage activation with important functions in innate and adaptive immunity • Also known as type II IFN Interleukin 4 • Main stimulus for the synthesis of IgE antibodies and for Th2 cell development • Produced by Th2 CD4 cells, mast cells and basophils • Inhibits macrophage activation