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