2. Chapter 17: IR to Infectious Disease In BIOL 304, we examined how pathogens can establish an infection in a susceptible host Re: the 7 components of pathogenicity!! On the other hand, humans are defended by: Physical barriers of epithelia and skin Surface chemicals, enzymes, acids Competitive flora Complement and sIg Phagocytic cells Specific/Adaptive IR

3. Still, infectious disease kills millions each year *Mostly, from bacterial and viral diseases

4. Anti-viral protection: Innate Type I IFN’s (α & β) are triggered from infected cells IFN’s bind to nearby cells and activate JAK-STAT pathway Induces several gene products which function to: –Degrade viral RNA –Shuts down PS in infected cells

5. Anti-viral protection: Adaptive Neutralization by Ab’s If Ig can bind to viral surface, prevents binding to target cell Or Ig can trigger Complement cascade Or bound Ig can agglutinate viruses to be phagocytized sIgA blocks binding to mucosal surfaces

6. Anti-viral protection: Adaptive Cell-mediated response Starts with T H 1 cells –Release of cytokines: IL-2, IFN-γ, TNF IL-2/IFN- γ act. NK cells IL-2 recruits T C cells Within 7-10 days, most virions are elim; parallels the development of Tc’s vs the virus

7. Evasion of Host defenses Block intracellular effects of IFN’s (Hep C) Block TAP function for Ag delivery to MHC I (HSV1 and 2)  prevents lysis by Tc’s Block formation of MHC I (Adenovirus, CMV) Block formation of MHC II (CMV, measles, HIV) Block complement fixation (Vaccinia binds to C4b*; HSV binds to C3b**) Antigenic variation (influenza, rhinovirus, HIV) Imunosuppression thru immune cell infection

8. Case study in viral mutation: Influenza HA binds to host cells NA aids in viral escape from host cells 8 RNA’s code for 10 proteins 3 types (A,B, and C) Type A resp. for pandemics –13 dif’t HA’s; 9 dif’t NA’s WHO nomenclature of Type A: Ex: A/Sw/Iowa/15/30 (H1N1)

9. Case study in viral mutation: Influenza Antigenic change is so complete no herd immunity can build Ag variation occurs in HA and NA from: Antigenic Drift Antigenic Shift 1934 – H0N1 1947 – H1N1 1957 – H2N2 1968 – H3N2 1977 – H1N1 1989 – H3N2 *Each Ag shift results in new pandemic outbreaks **current vaccine has both H3N2 & H1N1 strains

10. Anti-bacterial protection Bacterial infections are controlled by different IR’s (just as in viral infections) The type of IR centers on: Amount of inoculum Degree of virulence Extra- vs intra-cellular infection MO’s enter mostly through mucosal surfaces (resp/g.i tract/g.u. tract) Cuts/breaks in skin

11. IR’s to Extra-cellular infections Stim production of humoral Ab’s from local lymph nodes. Ab’s function to: –Opsonize bacteria  phagocytosis –Opsonize toxins  inactivation –Bind/activate complement  cell lysis –Stimulate/amplify inflammation  mast cell degran –Chemotaxis

12. Antibody mediated responses to extra- cellular bacteria

13. IR’s to Intra-cellular infections Induce a Delayed-type hypersensitivity rxn Cytokines, notably IFN-γ from CD-4 T cells activate MØ Cell-Mediated response

14. Evasion of Host Defenses Major steps to bacterial infection: –Attachment –Proliferation/growth –Invasion –Toxin-induced damage Host defenses operate during each one of these steps

15. Examples of pathogen control Classic example of imm bestowed by toxoid 1923-Ramon inactivated exotoxin w/ formaledhyde Significant drop in # of cases since then Toxoid administered in DTP immuniz @6-8 wks w/ boosters every 10 yrs Diptheria

16. Examples of pathogen control Inhaled bacilli ingested by alveolar MØ Bacilli grow in and lyse MØ Cytokines (esp IFN-y) produced by TH1 cells activates MØ to kill/ inhibit bacteria MØ wall off bacilli at focal points in the lungs – in tubercles (granulomas) MØ secrete IL-12 -> continue TH1 response 10% progress to chronic pulmonary or extra-pulmonary TB Tuberculosis

17. Emerging Infectious Diseases Newly described pathogens Those (which were once under control) showing rapid increases = “re-emerging infectious disease” Ex: TB Diptheria Causes of emerging/re-emerging diseases: –Overcrowding in cities among lower socioeconomic populations –International travel –Mass distribution of food commodity