Lecture 4

• What is the intracellular location, ligands, and functions of TLRs?


  Location: On eukaryotes and tissues and immune functions

  Ligands: Pathogen-associated molecular patterns (PAMPs) they are PRRs

  Functions: Initiate immune response, activate inflammatory pathways activate secretion of type one inferion
• What is the intracellular location, ligands, and functions of RIG-1?

  Location: Cytoplasm, on most cells Ligands: Viral RNA Functions: Detects viral RNA and activates antiviral immune response. cleaves
• What is the intracellular location, ligands, and functions of DNA sensors?

  Location: Cytoplasm Ligands: DNA or DNA-RNA hybrids Functions: Detecting foreign DNA, activating immune response, signalling
• What is the function of Interferons?

  IFN are produced in infected cells to inhibit viral replication
• What are the 4 main IFN effector pathways?


  ISG15 ubiquitin-like pathways

  MxGTPase pathway

  2',3' oligoadenylate synthase directed ribonuclease L pathway

  protein kinase R pathway
• What is the ISG15 pathway?

  ISG15 is a ubiquitin-like protein which becomes covalently bound to other cellular proteins. Proteins became ISGlyated so they last longer and have a high affinity= virus sensors, antivirals, molecules in IFN signalling
• MxGTPase pathway

  Myxovirus is a resistance protein that recognize+ binds viral proteins for early antiviral strategies
• Oligoadenylate synthase (OAS+RNaseL)

  Oligoadenylate synthetase (OAS) is expressed at low levels in the cytoplasm (Inactive)

  dsRNA activated OAS monomers to oligomerize

  Active OSA tetramers will synthesize oligomers of adenosine

  Adenosine oligomers activate RNase (cleave dsRNA)

  Cleaved dsRNA activates antiviral RIG-1 +MOA-5
• Protein kinase R pathway

  is constantly expressed at low levels in cytoplasm Inactive form

  belongs to a kinase family known to regulate protein synthesis in cellular stress

  Is then activated by dsRNA, and will autophosphorylate and dimerize. with then phosphorylate elF-2a

  Translation is halted
• Effectors of the innate and adaptive immune response?

  Innate: Macrophages

  Neutrophils,

  Dendritic cells- antigen-presenting cells for MHCII and cross-present MHCI Adaptive: T cells, helper or cytotoxic

  B cells produce antibodies

  Cytolysis: will make holes in infected cells bound by antibodies

  Inflammation: uses cytokines to activate inflammation

  opsonization: will coat virus particles to facilitate uptake by macrophages.

  Solubility: of immune complexes will break up antibody-antigen complex
• Natural killer cells will replicate upon viral infection, in responce to decreasing MHC class I surface expression on cells then target them for cell death = antiviral cytokines
• Cytokines are molecules that bind receptors on cells and stimulate gene expression.
• t-cells will respond to viral antigen on antigen presenting cells
• CD4+ helper t-cells which produce cytokines which stimulate antibody production of B-cells or activation of cytotoxic T cells

  CD8+ cytotoxic T-cells will kill infected cells
• antibodies are produced by B-cells, which bind virions to decrease infected cells. will work with the complement to lyse infected cells
• B-cell activation

  naive T-cells will exit circulation into B cell follicles to survy the environment