Download Chapter 17: IR to Infectious Disease

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 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
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 extracellular bacteria
IR’s to Intra-cellular infections
Cell-Mediated response
• Induce a Delayed-type
hypersensitivity rxn
• Cytokines, notably
IFN-γ from CD-4 T
cells activate MØ
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
Diptheria
• 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
Examples of pathogen control
Tuberculosis
• 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
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