chapter 17: ir to infectious disease in biol 304, we examined how pathogens can establish an...
TRANSCRIPT
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
Still, infectious disease kills millions each year
*Mostly, from bacterial and viral diseases
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
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
Anti-viral protection: Adaptive
• Cell-mediated response
• Starts with TH1 cells– Release of cytokines:
• IL-2, IFN-γ, TNF
• IL-2/IFN- γ act. NK cells
• IL-2 recruits TC cells
• Within 7-10 days, most virions are elim; parallels the development of Tc’s vs the virus
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
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)
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 DriftAntigenic Shift
1934 – H0N11947 – H1N11957 – H2N21968 – H3N21977 – H1N11989 – H3N2*Each Ag shift results in new pandemic
outbreaks**current vaccine has both H3N2 & H1N1
strains
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
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
Antibody mediated responses to extra-cellular bacteria
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
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
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
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
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