1. HOST RESPONSE TO VIRAL INFECTIONS

2. https://www.youtube.com/watch?v=Rpj0emEGShQ Flu Attack! How A Virus Invades Your Body

3. Basic viral structure Capsid: Protects genome Matrix proteins: Maintain virus structure Glycoproteins: assist in entering the cell without damage (human viruses are enveloped) SYMMETRICAL SHAPE

4. Virus infection and replication

5. Immunity to virus infection Virus are obligate intracellular parasites which need to enter the body, replicate in a cell and spread. For immunity, these characteristics must be blocked

6. INNATE IMMUNE MECHANISMS First line defences pH – stomach Ciliary action – trachea mucous production Skin – limits entry impenetrable. Epithelia cells, lysosyme, Commensal bacteria

7. Most common respiratory viruses: Adenovirus Influenza virus Respiratory syncytial virus Rhinovirus Respiratory system is a closed system designed to prevent host invasion derived from inhaled air Symptoms: cough, runny nose (rhinorrhoea), airway mucus production (bronchitis), fever, scratchy throat (pharngytis), congestion up to 14 days. Susceptibility Immunocompromised Infants (immature immune system) HIV infected Underlying pulmonary disease ie Cystic fibrosis, chronic lung disease, asthma Respiratory system – virus entry point

8. Major Components of Viral Immunity Innate response Adaptive response Soluble factors Interferons ,  and  Antibodies CellsNK cells Phagocytes T lymphocytes CD8 cytotoxicity CD4 cytokines

9. Host response to acute virus infection e.g. influenza virus NK cells (and interferon) are detected first Cytotoxic T cells are then activated Antibody (neutralising) then appears

10. Respiratory system – innate immune defences 1. Anatomical defences Nasal cavity – air filtration Ciliated cells – mucociliary clearence 2. substances Epithelial lining fluid – lysozyme defensins Neutrophils –myloperoxidase etc

11. Respiratory system – innate immune defences 3. Phagocytosis Alveolar macrophages

12. Interferon (IFN) Induce a state of antiviral resistance in uninfected cells. Enhancement of various immune effector mechanisms e.g. natural killer cell activity, macrophage function, MHC Class I and II levels Different IFNs: IFN  and  - type I IFNs IFN  - type II IFNs IFN  and  are produced by cells infected by viruses IFN  is produced by antigen activated T cells and NK cells

14. NK cell mediated killing Increased by exposure to interferon alpha or beta and also to interferon gamma, TNF alpha or IL12 from phagocytes.

15. Natural Killer (NK) cells Recognise cells which do not express MHC class I molecules No antigen specificity Have cytotoxicity function i.e. can lyse target cells Recognition of target cells by Tc cells and NK cells

16. Antibody responses to viral infection

17. ANTIBODY RESPONSE Antibodies provide a major barrier to prevent virus spread between cells and different tissues. Recognise antigens on virus particles and on the surface of virus-infected cells. Three important types against viruses: IgG, IgA, IgM

18. Antibody Response IgM in 5-10 days (serum) lasts for 3 months. IgG maximum 20-30 days later. Mainly IgG1 and IgG3. Lasts one year. IgA found 2-5 days in lung. Peaks around day 10. Later in serum.

19. Antiviral Effects of Antibody TargetAgentMechanism Free virusAb alone Ab + complement Blocks binding to cell Blocks cell entry Blocks uncoating of virus Damage to envelope Blocks virus receptor Virus-infected cellsAb + complement Ab bound to infected cells Lysis of infected cells Opsonisation for phagocytosis Ab dependent cytotoxicity by NK. Neutrophil or macrophages

20. Cellular immunity mediated by T lymphocytes MHC class I restricted Recognise virally infected cells Lysis (destruction) of these cells CD8+ cytotoxic T lymphocytes (CTL) CD4+ T helper lymphocytes MHC class II restricted Antigen present by professional APCs Provide help for immune system (e.g. cytokines, interferons)

21. Antigenic drift in influenza virus avoids neutralising antibodies. Avoiding the immune response

22. Antigenic Drift: Slow change in epitopes (principally HA) by mutation: results in epidemics seen each winter Antigenic Shift: Major change due to reassortment when two or more viruses infect the same cell. Mixing of segmented genomes. Results in brand new virus and thus pandemics

24. What actually happens to the virus NK, Interferon's and later CD8 cytotoxic cells stop replication. Proteins such as complement, antibody and surfactant, bind viral particles. These are removed by Phagocytes such as neutrophils and macrophages.

25. Summary Understanding the immune response to infection can inform vaccine development. Important immune effector mechanisms directed against virus infection 1.innate immunity (e.g. interferon, NK cells) 1.adaptive immunity (e.g. antibodies, T cells)

26. Influenza. In the severe outbreaks of influenza such as those in 1919 and 1957 many people actually died from bacterial infection. Since been Shown that Influenza causes a long term reduction in airway macrophage activity which in turn blunts the response to bacterial infection.