1 / 29

ASPECTS OF INNATE IMMUNITY

ASPECTS OF INNATE IMMUNITY. EVOLUTION OF THE IMMUNE SYSTEM. Fujita T (2002) Nat Rev Immunol 2 :346-353. EVOLUTION OF THE IMMUNE SYSTEM. Sun JC et al. (2014) EMBO J - in press (DOI 10.1002/embj.201387651 ). INNATE/NATURAL IMMUNITY. RECOGNIZING RECEPTORS.

mea
Download Presentation

ASPECTS OF INNATE IMMUNITY

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ASPECTS OF INNATE IMMUNITY

  2. EVOLUTION OF THE IMMUNE SYSTEM Fujita T (2002) Nat Rev Immunol 2:346-353.

  3. EVOLUTION OF THE IMMUNE SYSTEM Sun JC et al. (2014) EMBO J - in press (DOI 10.1002/embj.201387651 )

  4. INNATE/NATURAL IMMUNITY RECOGNIZING RECEPTORS PROTECTIVE MECHANISMS Enzyme systems Multicellular (Metazoa) Sea urchin 600 million years Toll-like receptors C. elegans Drosophila 700 millionyears complement

  5. PRINCIPLES OF INNATE IMMUNE RECOGNITION PRRs Source: http://www.m.kanazawa-u.ac.jp/eng/gaiyou/dep03/dep3-01.html

  6. CLASSES OF PRRs TLRs: Toll-like receptors NLRs: NOD-like receptors RLHs: RIG-I-like helicases CLRs: C-type lectin receptors ALRs: AIM2-like receptors Thomas CJ and Schroder K (2013) Trends Immunol 34:317-328.

  7. TLR TLR3 MEMBRANE CONSERVED RECEPTORS/SENSORS THAT DETECT DANGER SIGNALS Fibroblast Epithelialcell DC LRR TIR domain CELL MEMBRANE Bacteria MEMBRANES OF INTRACELLULAR VESICLES virus TIR: Toll-Interleukin Receptor signaling domain

  8. TOLL RECEPTORS ACTIVATE PHYLOGENETICALLY CONSERVED SIGNAL TRANSDUCTION PATHWAYS TLR3 TLR4 Fungus CD14 Protease Spätzel Toll TRIF Tube IRF3 Relish Pelle Cactus NFkB IFN Peptide Bacterium LPB LPS TLR4 CD14 MyD88 IRAK IL-1R associated Kinase Inflammation Acute phase response Danger signal IL-6 Drosophila Mammals

  9. TLR4 activation can lead to the production of either inflammatory cytokines or antiviral type I interferons (IFNs). Source: http://www.sabiosciences.com/images/pathway7/7/tlr_figure_1.jpg

  10. TLR SIGNALING – THE BASICS A Szabo and E Rajnavolgyi (2013) Am J Clin Exp Immunol 2:195-207.

  11. RLH SIGNALING PATHWAYS

  12. NLR ACTIVATION AND SIGNALING

  13. Valiante N et al. (2008) Nat Med14:1318-1319.

  14. Cytokines/chemokinesproducedbyactivatedmacrophages - local and systemiceffects Szisztémás hatás

  15. THE ACUTE PHASE RESPONSE IL- 6 Mannose binding lectin/protein MBL/MBP COMPLEMENT C-reactive protein (CRP) COMPLEMENT Fibrinogen Serum Amyloid Protein (SAP) Mannose/galactose binding Chromatin, DNA, Influenza Liver IL-6 induces the production of acute phase protiens

  16. THE INTERFERON RESPONSE

  17. VIRUS-INDUCED TYPE I INTERFERON PRODUCTION Type I IFN receptor IFN response Virus IFN- IRF-3 NFB AP-1 IRF-3 IFN- paracrine IFN- IRF-7 autocrine Infected cell IFN response IFN- subtypes IRF: interferon regulatory factor

  18. JAK2 JAK2 TYK2 JAK1 TYK2 JAK1 JAK1 JAK1 STAT1 STAT1 STAT1 STAT2 P P P P STAT1 STAT1 P STAT1 STAT2 P P P Type I. IFN receptor Type III. IFN receptor (IFNλ) Type II. IFN receptor IFNAR1/2 IFNLR1 IL-10R2 IFNG1/2 Plasma membrane Cytoplasm STAT1 STAT1 STAT2 ISGF-3 IRF9 Interferon-stimulated genes Nucleus GAS: Gamma Activating sequence ISG15, Mx, OAS and PKR ISRE GAS – promoter elements Interferon-stimulated regulatory elements Antiviral immunity Antimycobacterial immunity

  19. EFFECTS OF TYPE I INTERFERONS Plasmacytoid dendritic cells produce 1000x more type I interferon than other cells NATURAL INTERFERON PRODUCING CELLS – IPC After viral infection they are accumulated at the T cell zone of the lymph nodes

  20. Oligomer accumulation in cytoplasmic membranes (e.g. ER) MxA oligomer MxA monomer (Cytoplasm) Trapped viral components MxA (Nucleus) ISRE Inhibition of translation P eIF2a eIF2a synthetized pppA(2’p5’A)n inactive RNaseL monomer Active PKR dimer Active OAS1 tetramer active RNaseL dimer Induction by viral RNAs Induction by viral dsRNA Inactive PKR monomer Inactive OAS1 monomer cleaved RNA (Cytoplasm) (Cytoplasm) OAS1 (Nucleus) PKR (Nucleus) ISRE ISRE Establishment of the „antiviralstate” Mechanism of actionof MxA, OAS1 and PKR

  21. COMPLEMENT ACTIVATION COMPLEMENT Lysis of bacteria Complement-proteins Inflammation Chemotaxis Bacterium Lectin pathway Alternative pathway Complement-dependent phagocytosis MECHANISMS OF INNATE IMMUNITY Antigen + Antibody ACQUIRED IMMUNITY Few minutes – 1 hour Enzymes get fragmented, complement activity can be exhausted

  22. Degradation PRR ACTIVATION Bacterium Intracellular killing Phagocyte Uptake Antigen + Antibody ACQUIRED IMMUNITY Antigen presentation T cell ACQUIRED IMMUNITY MECHANISMS OF INNATE IMMUNITY PHAGOCYTOSIS 0.5 - 1 hours The amount of internalized particles is limited

  23. INFLAMMATION – ACUTE PHASE RESPONSE PRR TNF- neutrophil LPS IL-12 NK-cell TNF- IL-1 IL-6 Bacterium IFN macrophage cytokines Few hours ACUTE PHASE RESPONSE LPS (endotoxin) (Gram(-) bacteria) DANGER SIGNAL ACTIVATION TNF- IL-1 IL-6 Kinetics of the release of pro-inflammatory citokines in bacterial infection Plasma level hrs MECHANISMS OF INNATE IMMUNITY

  24. Source: https://www1.uni-frankfurt.de/fb/fb16/institut/imm/Research/index.html

  25. Source: https://restoreimmunehealthdotcom2.files.wordpress.com/2012/08/natural-killer-cell.png

  26. ACTIVATION OF NATURAL KILLER CELLS NK-CELLS PRR Virus-infected cell RECOGNITION ACTIVATION Lysis of infected cell IFN IL-12 RECOGNITION OF ALTERED HOST CELLS NK-cells Relative level/activity Kinetics of the activity of the complement system and NK cells in virus infection Complement system days MECHANISMS OF INNATE IMMUNITY

More Related