Download Failures of body`s defenses Immunopathology

Failures of body’s defenses
Immunopathology
Evasion and subversion of the
immune system by pathogens
The immune system is still the big black box
Environment
Immune system
Tolerance
self
Non-self
Dangerous
Pathogenic
Little light at
the end of the
tunnel
Immune
response
PATHOGENS HAVE SHORT GENERATION TIME
PATOGENS
Virus
Bacteria
3 hrs
Viruses
3 hrs
Diversity
Fast development
parasites
Humans have longer generation time,
Need a sophysticated protection system
Birth
Development
education
Reproducrion
at 35
Genetic variation prvents long-term immunity
Highly variable capsular polysaccharide molecules---- serotypes
High rate of mutation and recombination help influenza virus
to escape immune recognition
(Antigenic drift)
ORIGINAL ANTIGENIC SIN
High rate of recombination help influenza virus to escape immune
recognition Large changes can occur rapidly by recombination
between virus particles made in different hosts
Viruses may interfere with the presentation of viral antigens
(HSV, EBV, CMV, etc)
Strategyies of Human cytomegalovirus (HCMV)
Gene rearrangement is used by
Trypanosomes to change cell surface antigens
Cell surface glycoproteins are encoded by separate genes
Approx. 1000 vatiable surface glycoproteins (VSG)
Antibody controls parasite, but always a new variant emerges
Deposition of immune complexes
Inflammation
CNS involvement, neuronal damage, sleeping sickness--- coma
The pilin protein of Nesseria gonorrhoeae is also variable
and only one is expressed at any time.
‘Seek and hide’
by Listeria monocytogenes, an intracellular bacterium
Bacterial superantigens bridge α:β T-cell
receptors and MHC class II molecules in the
absence of a specific peptide.
Macrophages are responsible for
Phagocytosis of bacteria
and other foreign cells and for activation
of other immune cells
Macrophage
Bacteria
Normally ingested
bacteria and
other things get sent
to the lysosome
for destruction
by low pH and
proteolysis
Uh oh!
bacterium
But the TB bacterium
has a better idea-It remodels the
endosome to be its
new home!
Avoiding the lysosome
also reduces presentation
of bacterial peptides
to the immune system by
the MHC proteins