Parasite Survival Strategies and Persistent Infections Flashcards
avoiding innate IR
antiphagocytic strategies
toxins prevention of oponisation prevention of contact inhibition of phagolysosome fusion escape into the cytoplasm resistance to killing
how is ciliary action avoided?
bordetella pertussis interferes with the cilia
how is the complement alternative pathway inhibited
outer surface (e.g. capsule) prevents either C activation or access to fixed C3b
bacterial membrane is resistant to MAC complex formation
Decoy proteins divert C components away from bacterial surface
what does Neisseria spp. produce in the host
produces iron-binding molecules -steal iron from transferrin
blocking interferons (INF)
host cells respond to dsRNA/RNA from infecting microbes by producing INF
some viruses are poor inducers of INF, (e.g. hapatitis B) or produce molecules that block action of INF in cells (e.g. HIV)
examples of how lymphocytes avoided (adaptive IR)
viruses, very good at avoiding immune defenses
no extensive tissue damage, better survival
latent viruses -remain hidden to resurface later
evasion strategies for adaptive IR
hit and run
concealment of antigens
antigenic variation
immunosuppression
Hit and run
microbe invades, multiplies and sheds within a few days
too quick for adaptive IR activation (e.g. rhinovirus, rotavirus)
concealment of antigens
hide in host cells
-prevent Ag presentation by MHC (adenovirus protein + class 1 MHC prevent its passage to cell surface)
hide at sites not exposed to circulating lymphocytes (skin. CNS, testis, placenta)
molecular mimicry -fragment similar to host cells
covering microbial surface with host molecules
hide at sites not exposed to circulating lymphocytes
IgA may interact but not enough to kill, only reduce disease
can hide in many glands
skin, intestinal lumen, secretions, testis, placenta, CNS
most privileged location=host DNA (occupied by retrovirus) -retroviral DNA
as long as viral products not expressed, remain undetected indefinitely (HIV)
molecular mimicry
microbial antigens look like host cells
streptococcal M-protein and human heart (streptococcal biogenis)
other variants of streptococci colonize local heart tissue
covering microbial surface with host molecules
antibodies can only attach in useless upside down position on the FC portion
antigenic variation
changing cell surface antigens -> escape immune system
during infection of single individual
during spread throughout population
eg relapsing fever, Borrelia spp
what the three molecular mechanisms for antigenic variation
mutation -nucleotide change
recombination -rearrangement of genes
gene switching -turn genes on and off
antigenic variation: mutation
e.g. influenza virus -spreads through population
genes encoding hemagglutinin and neuraminidase undergo mutation
leads to Ag change that makes them unrecognizable by B and T memory cells
=”antigenic drift”
also rhinovirus and enteroviruses
Antigenic variation: recombination
e.g. influenza A virus
genetic shift
sudden chnage in surface Ag can occur when genetic material between two different viruses recombine after infecting same host
gives rise to a completely new virus
Antigenic variation: gene switching
e.g. African trypanosome -genes for 1000 different surface molecules
can switch one gene weekly for Ag
e.g. Neisseria gonorrhoaea -changes bacterial surface properties as infection proceeds
initially expresses pili and outer membrane proteins allowing attachment to urethral epithelial cells
once established, switch those off so less sticky for phagocytes, allows for reinfection
immunosuppression
infection of immune cells
T cells -HIV, measles
B cells -EBV
macrophages and dendritic cells -HIV
interference with immune response
-reduction in MHC-1 expression by adenovirus
IgA protease -N. gonorrheoae and S. pneumoniae
examples of disease that are persistent infections with shedding
epstein-barr virus
tapeworms
examples of persistent latent infections
herpes simplex virus VZV reactivating tuberculosis malaria chicken pox enters lymph nodes -> shingles
examples of persistent slow infection following acute infection
SSPE
PML
HIV
HTLV-1 (leukemia)
examples of persistent slow infection (no acute stage)
CJD
kuru prions
hard to treat
microbes may persist as
continuously infectious form (hep B virus in blood)
low infectivity (adenovirus in tonsils and adenoids)
non-infectious (latent virus (HSV -viral DNA persists for life in host nerves)
importance of latent infections
reactivation
association with chronic infections (HIV->AIDS)
association with cancer (HBV->liver cancer)
persistence in community
reactivation
typically in immunocompromised patients (disease, cancer, tissue transplant, elderly, pregnancy)
Stage A: stimulus-> HSV: sunlight, fever, hormonal shifts
Stage B: spread and replication
HSV: travel via sensory axon to skin/mucosal surface
infection of epithelial tissue and form virus-rich vesicles -cold sore
arrested by IS before lesion forms: itchy, tingly sensation w/o cold sore
