virus 4

• Innate Immune Response

   • First line

   • Provides rapid protection −Broad specificity 

  −No antigen processing

  −No memory recall 

  −Short duration 
• The major players in the innate response 

  • Neutrophils

  • Antigen Presenting Cells

  −Macrophages and dendritic cells

   • Natural Killer Cells
• Natural Killer (NK) Cells:

  • Seek out and destroy virus-infected cells.
  • Recognize stress markers on infected cells.
• neutrophiles : predominant cell in innate

  phagocytose pathogens

  delepation may lead to serve infection and mortality
•  Natural Killer (NK) Cells = Identify markers of stress on the infected cells 
• natural killer cells =

   −Activating receptor

   −Inhibiting receptor (prevents NK cells from killing healthy cells)
• NK = infection = less inhibition and more activation = NK kills bound cell = by release of perforin and induces apoptosis and interferon gamma
• antigen presenting cell = dendritic and macrophage cells
• Antigen Presenting Cells

   • Carry immunoglobulin Fc and C3b receptors =promote phagocytosis

  • MHC 2 = T cells = Cytotoxic t cells and CD4 = cell mediated

  • Initiate the adaptive immune response
• How is a virus recognised as foreign? - PAMPS viruses have

  • CpG motifs in DNA virus
  • Double stranded mRNA
  • Uracil rich SS RNA
• PAMPS = pathogen associated molecular patterns, are molecules that are produced by pathogens and are recognized by the immune system
• pamps

  • CpG motifs DNA viruses
  • Double-stranded RNA
  •  Uracil-rich, single-stranded RNA
• What receptors recognise PAMPS

  • Toll - like receptors = to find viruses extracellular
  • Cytoplasmic receptors = Rig -1 NOD2 and MDA 5
• Toll-Like Receptors 

  • Recognise extracellular viruses

  • 2, 4 = cell surface = for viruses
  • 8, 9 = endosome
• TLR-3 binds ds RNA
•  TLR-7 binds Uracil-rich ss RNA (e.g. HIV)

   TLR-8 binds ss RNA

  TLR-9 binds CpG motifs within viral DNA
• Cellular Pattern Recognition Receptors = RIG-1 and MDA-5 
• RIG-1

  ▪ Recognises ssRNA
•  MDA-5 

  ▪ Recognises ds RNA
• cytoplasmic PRRs =

  production of pro-inflammatory cytokines and type 1 interferons
• Stimulation of both Tolll -like receptors and cytoplasmic PRR lead to either activation of

  • NF-kB = proinflamamtory
  • IRF/3 = type 1 interferons
• NF-kB = proinflamamtory

  • NK-κB-dependent cytokine response IL1, TNFα , INFγ 
• Interferons

  • Protects adjacent cells from infection
  •   Inhibition of viral replication 
  • Helps activates T-cell mediated immunity
• Interferons−Activation of macrophages

  −Up-regulates MHC receptors on virus-infected cells
• types 1 of interferon

  alpha and beta
• IFNα and IFNβ (type 1)

  • Activate genes that have antiviral activities 

  −dsRNA dep protein kinase R 

  −RNase L 
• IFNα and IFNβ (type 1)

  • Helps stimulate MHC class I (enhance presentation of viral peptides to T cells) 
  • Activates NK cells 
  • Induces apoptosis
• proinflammatory cytokines = INF gamma / interferon gamma
• IFNγ (type 2, proinflammatory) =- innate and adaptive

   Produced by NK cells and T lymphocytes

  •  • Enhances MHC expression on APCs
  • Enhances the cytotoxic activity of T cells, macrophages and NK cells
• more important role of INF gamma than INF alpha or Beta .
• Humoral = antibody =virus outside cells
• cell mediated = cytotoxic t -cells and t helper
• − T Helper cells (TH ) CD4+ 

  • MHC 2
  • Activate macrophages
  • cytokines
  • adaptive
•  Cytotoxic T cells (CTLs) CD8+  MHC 1

  • Kill virus-infected cells

   • Cytokines that eliminates viral RNA 
• Humoral Immune Response B lymphocytes 

  • Resident in the lymphatic tissue

   • Recognise Ag in their native form (no processing)
• B cell activation

  • activates = binding of antigen to receptor
  • Clonal expansion = t - helper cell activation
  • Class switch Igm = IgG = antibodies
  • memory cells
•  Antibodies early on are low affinity (poor binding)

  B cells evolve by hyper-mutation in the V regions to produce high affinity binding antibodies later on
• IgM first antibody produced
• igG important for detecting virus circulation in the blood
• igA = mucosal surface and GI tract