BIO 370 Lecture Notes - Lecture 35: West Nile Fever, Pattern Recognition Receptor, Innate Immune System
The CCR5 Gene
• It is a receptor on white blood cells and so in involved in the immune system.
• A mutation occurred in Northern European populations and has spread apparently in
response to the plague
– CCR5-Delta32 missing a series of amino acids
– So the potei does’t eted to the sufae of the ell.
• The mutation confers resistance to several pathogens including HIV-1.
• M-tropic strains of HIV use the CCR5 receptor protein to gain entrance into white blood
cells.
• Individuals that are homozygous for the CCR5-Delta32 allele are resistant to so-called
M-tropic strains of HIV.
• But the Delta32 allele may increase susceptibility to West Nile encephalitis
• But there are always tradeoffs
• But the Delta32 allele may increase susceptibility to West Nile encephalitis and tick-
borne encephalitis.
What must the human immune system be able to do?
The human immune system must 1) recognize, and 2) eliminate or incapacitate microbial
pathogens.
Beause a ultiellula host ould ee keep up ith a pathoge’s aility to generate
genetic variation and evolve rapidly, immune systems rely on a number of tactics that limit
the ability of pathogen populations to outrun their hosts by virtue of rapid natural selection.
One strategy is to target components of the pathogen that are highly conserved and cannot
easily be changed.
Our innate immune response detects the presence of pathogens using pattern recognition
receptor molecules that bind to common components of pathogens known as pathogen-
associated molecular patterns.
These receptors recognize highly conserved components of pathogens, such as the
peptidoglycan polymer that makes up the bacterial cell wall, the lipopolysaccharide
molecules and lipoproteins in Gram-negative bacterial cell membranes, and the flagellin
protein of bacterial flagella.
E.g., some bacterial cell wall components must interact with the host in such a way as to
get the host to do hat it ats. If thei ada is alas o, the the eoe isile
to the host!
The pattern recognition strategy does not work well against viruses because:
Viruses have few conserved external structures.
Many viruses are produced by budding from a host cell and, therefore, are wrapped in a
membrane layer that is structurally the same as that of the host.
find more resources at oneclass.com
find more resources at oneclass.com
Viruses replicate within host cells; therefore, in addition to finding and eliminating free virus
particles, the immune system must also locate and deal with infected host cells.
One major recognizable difference is that properly functioning eukaryotic cells should not
contain long double-stranded RNAs, whereas cells infected with viruses often do. The
innate immune system responds aggressively to such double-stranded RNAs within a cell.
Senescence
While the eventual consequence of senescence is death, the two are not synonymous.
While average life span or maximum life span are correlates of the senescence rate,
senescence has effects reaching beyond longevity.
We see these effects dramatically in the decline in human athletic performance with age.
Senescence is not an evolved developmental program. It is a by-product of other
adaptations.
Thus, what we want to explain is not the evolution of senescence, but rather why we have
not seen the evolution of adaptations that prevent aging.
An Evolutionary View of Senescence
Selection on Early- and Late-Acting Mutations
• Two things are at work here
• Fecundity and Numbers
– Early acting positive mutations increase fecundity a great deal
• Before reproductive peak
• MORE individuals at play
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
It is a receptor on white blood cells and so in involved in the immune system: a mutation occurred in northern european populations and has spread apparently in response to the plague. Ccr5-delta32 missing a series of amino acids. So the p(cid:396)otei(cid:374) does(cid:374)"t e(cid:454)te(cid:374)d to the su(cid:396)fa(cid:272)e of the (cid:272)ell: the mutation confers resistance to several pathogens including hiv-1, m-tropic strains of hiv use the ccr5 receptor protein to gain entrance into white blood cells. Individuals that are homozygous for the ccr5-delta32 allele are resistant to so-called. M-tropic strains of hiv: but the delta32 allele may increase susceptibility to west nile encephalitis, but there are always tradeoffs, but the delta32 allele may increase susceptibility to west nile encephalitis and tick- borne encephalitis. The human immune system must 1) recognize, and 2) eliminate or incapacitate microbial pathogens. One strategy is to target components of the pathogen that are highly conserved and cannot easily be changed.
