Week 4

• Innate immunity

  Exhibit neither antigen specificity nor memory
• Innate immunity


  • Provide critical line of first defense against viral infections
  • Constantly present
  • Operational immediately after viral infection
  • Only immune defense available for the first few days of viral infection
• Primary physical and chemical defenses

  • Skin
  • Mucous membranes
  • GI tract
  • Respiratory tract
• Skin

  • Dense outer layer of keratin that acts like a mechanical barrier
  • Low pH
  • Presence of fatty acids
  • Dryness
• Mucous membranes

  • Virucidal proteins
• GI tract

  • Mucous membrane oral cavity and esophagus that is refractory to viruses
  • Acidity of stomach
  • Alkalinity of intestine
  • Layers of mucus covering the gut
  • Lipolytic activity of bile
  • Proteolytic activity of pancreatic enzymes
  • Defensins with antiviral activity
• Respiratory tract


  • Mucociliary blanket
  • Temperature gradient between nasal passages and alveoli
  • Role in localization of infection
• Rhinoviruses


  Replicate well at 33C and infect upper respiratory tract
• Influenza virus


  Infects lower respiratory tract
• Natural killer cells


  • Mediates cell death of virus infected cells via apoptosis
  • Synthesize and release a variety of cytokines that stimulate their own proliferation and cytolytic activity (type II interferons and interleukins)
• Cellular pattern recognition receptors

  • Cells at portals of virus entry possess surface receptors that recognize specific pathogen-associated molecular patterns
  • Toll-like receptors
• Interferons


  • Group of cytokines that are secreted by somatic cells in response to viral infects and other stimuli
  • Possess potent antiviral, immunomodulating and anticancer properties
  • Show no virus specificity
  • RNA viruses are stronger inducers of interferon
  • Orally inactive, should be administered by parenteral route
• Type I interferons


  • IFN-alpha (leukocyte interferon, produced in large quantities by plasmacytoid dendritic cells)
  • IFN-beta (fibroblast interferon, secreted by virus-infected fibroblast)
• Roles of type I interferons

  • Inhibit virus replication in host cells
  • Activate natural killer cells to kill infected cells
  • Increase expression of MHC-1 molecules and antigen presentation
  • Stimulate differentiation of monocytes into dendritic cells
  • Maturation of dendritic cells
  • Stimulate memory T cell proliferation
  • Activate latent ribonuclease
  • Induce synthesis of matrix proteins that bind and trap viral nucleocapsid and inhibit virus assembly
  • Induce synthesis of protein kinase R
  • Prevents initiation of translation of viral RNA
• Type II interferons

  IFN-gamma

  Mostly immunoregulatory, produced by antigen-stimulated T cells and natural killer cells
• Type III interferons

  IFN-lambda1, IFN-lambda2, IFN-lambda3

  Expressed in response to viral infections and activation of toll-like receptors, primarily functions as immunoregulator
• Adaptive immunity

  Included humoral and cellular components

  Antigen specific

  stimulate long-term memory after infection

  Responses take time to develop

  Mediated by lymphocytes that possess surface receptors that are specific to each pathogen

  Stimulates long-term memory after infection
• Humoral immunity


  Mediated principally by antibodies released from B lymphocytes
• Cellular immunity


  Mediated by T lymphocytes
• Internal viral antigens


  Usually elicit protective cell mediated immune response
• Surface antigens


  Elicit protective humoral and cell mediated immune responses
• Antibody-mediated immunity (humoral immunity)

  • Antibodies may be directed against viral proteins on free virions or against viral proteins expressed on surface of infected cells
  • Virus neutralization
  • Opsonization
  • Clumping of viruses (immunocomplex formation) = agglutination
  • Activation of complement system
  • Antibody dependent cell mediated cytotoxicity
• Cell mediated immunity

  • CD4 helper T lymphocytes (activation of macrophages, inflammation, stimulation of B lymphocytes)
  • CD8 cytotoxic T lymphocyte (killing of infected cell)
• Antigenic plasticity

  • Rapid changes in the structure of the viral antigen
  • May be the result of mutation, reassortment, or recombination
  • Virus may become resistant to immunity generated by previous infection
  • Due to change in antigen structure
• Antigenic multiplicity


  Antigenic variants with little or no cross-reactivity
• Negative cytokine regulation

  virokines

  viroceptor
• Viroceptor

  Some viruses encode proteins that are homologous to receptors for cytokines

  competitive antagionist
• Virokines

  Some viruses synthesize proteins which are homologs of cytokines/interferons
• Epidemiology of viral diseases

  Study of the determinants, frequency, dynamics, and distribution of viral diseases in populations
• Virus epidemiology


  • Characteristics of the virus
  • Host and host population
  • Behavioral, environmental, and ecological factors that affect virus transmission from one host to another
• Role of epidemiology in viral diseases

  • Identify and/or clarify the role of viruses in the etiology of disease
  • Understanding the interactions of viruses with environmental determinants of disease
  • Determining factors affecting host susceptibility
  • Unraveling modes of viral disease transmission
  • Studying the impacts of viral disease on health, economy, and society
  • Studying role of infectious pathogens in the pathogenesis of chronic noncommunicable diseases, such as oncogenic viruses in cancer
  • Large scale testing of vaccines and drugs (clinical trials)
• Why study epidemiology of viral diseases?

  Risk of infection and/or disease in an animal or animal population determined by
• Case fatality


  Number of deaths among the clinically ill animals
• Mortality rate

  Number of animals in a population that die from a particular disease over a specified period of time
• Morbidity rate


  Percentage of animals in a population that develop clinical signs attributable to a particular virus over a defined period of time
• Incidence


  Number of new cases that occur in a population over a specified period of time
• Incidence rate


  Measure of occurrence of infection or disease in a population over time
• Prevalence


  Number of occurrences of disease, infection, or related attributes in a population at a particular point of time
• Sporadic viral disease


  Viral diseases occurring occasionally, singly, or in scattered instances, and in irregular and haphazard manner
• Enzootic viral disease


  Constant presence of viral disease within a given geographic area or population