7 - fungi and parasites Flashcards
why are chronic infections common caused by fungi and parasites
they have many adaptions
features of fungi
can be uni or mulitcellular
often commensal
contribute to nutrient recycling
can be dispersed by airborne spores
unicellular fungi
yeasts
multicellular fungi
filamentous
endemic mycoses
groups of fungi that occupy ecological niches
geographically located due to climate
often thermally dimorphic
example of commensal fungi
microbial flora
e.g.candida albicans
example of fungi dispersed by airborne spores
aspergillus fumigatus
reaches terminal air spaces of lungs
types of mycoses
endemic mycoses
environmental saprophytes
human commensal fungi
examples of endemic mycoses
histoplasma
coccidiodes
blastomyces
paracoccidiodes
where are histoplasma found
often mississipi/ohio
bird/bat poo (guano) in soil
where are coccidiodes found
arid desert areas (south west USA)
where are blastomyces found
near lakes/river valleys
where are paracoccidiodes found
tropical and sub forests in South america
examples of environmental saprophytes
aspergillus rhizopus absidia mucor cryptococcus
features of environmental saprophytes
often opportunistic and invasive
dangerous
where is aspergillus often found
decaying veg matter
where is cryptococcus found
soil with pigeon poo (guano) and eucalyptus trees
examples of human commensal fungi
candida albicans
dermatophytes
where is candida albicans often found
bowel
pharyngeal flora
where are dermatophytes found
keratinized tissue
fungi mortality rate?
high in infected populations
example of high mortality rate of fungi
Aspergillus fumigatus causes more than 200,000 life threatening infections per year
persistant superficial infection of candida albicans
causes disription of mucosal barriers
e..g thrush
candida albicans in immunocompromised
disseminates to life-threatening diseases
prevalence of candida albicans
most common human infection
4th most common nosocomial bloodstream infection in USA –> very expensive for government
candida albicans virulence
reproduces asexually (budding) dimorphic in repsonse to microenvironmental signals
dimorphic
transition from yeast to filamentous
role of yeast form candida albicans in infection
disseminates easily in bloodstream
role of filamentous c. albicans in infection
facilitates invasion and evasion of phagocytosis
if c albicans has no dimporphic switch
it is non pathogenic
innate host recognition of fungi
interactions with cell wall components
PAMPs
examples of fungi PAMPs
glucans
mannans
galactans
dectin-1
c-type lectin
highly conserved on surface of dendritic cells
important in anti-fungal immunity
role of c-type lectin carbphydrate recognition domain
mediates recognition of B1,3-glucans and B1,6-glucans and zymosan
dectin-1 interacts with ITAM in cytoplams
tyrosine phosphorylation
then acts together with TLRs to induce inflammatory cytokines and ROS
ITAM
immunoreceptor Tyrosine-based Activation Motif
important in signal transduction
found in T cells, B cells and Fc domains
4 examples of PRR that recognise fungi/parasites/viruses
Dectin-1
Dectin-2
Mincle
CLEC5a
knock out dectin-1 genes in mice
infect with candida albicans
what happens
mice susceptible and die
evidence that dectin-1 is important in anti-fungal immunity
importance of TLRs
distinguish between pathogenic molecules and normal apoptotic particles
what to TLRs stimulate
cytokine production and secretion –> inflammatory response
initiation of adaptive immune response
what do most TLRs signal through
MyD88
what is MyD88
myeloid differentiation factor 88
adaptor protein
role of MyD88
binds to TLR after activation by fungal component (PAMP) and CD14
initiates signalling cascade
Syk
enzyme
(spleen tyrosine kinase)
important in signal transduction
MBL
mannose-binding lectin
mannose binding lectin
collectin protein
opsonin
coupled to complement pathway via MASPS
bind to MASPS to cause conformational chage
oxidative burst killing mech
kill by rapidly producing and releasing ROS
what is chromoblastomycosis
a chronic but non-fatal fungal infection of the skin and subcutaneous tissue
usually caused by F. Pedrosi
helminth
class of parasite that can cause disease in humans
why do helminths require an intermediate host
they do not replicate within the host
examples of helminth intermediate host
soil
water
3 larval stags of sexual reproduction of helminths
nematodes
trematodes
cestodes
what is schistosoma
the most important trematode (fluke) infection of humans
vector of schistosoma
water snail
vector of schistosoma
water snails
become infected by eggs in fresh water
miracidia mature and multiply to release more cercariae
which stage is dangerous for causing infection of schistosoma
motile
fork-tailed cercariae
what happens when free swimming cercariae come in contact with host skin
use proteases and muscular action of oral sucker to penetrate host skin
head enters body
shed tails
what do cercariae transition into
schistosoma and then into a schistosome
where do immature schistosomula migrate to
the liver microcirculation to mature
male/female interaction of schistosomula
females reside in a canal within the male
pairs then migrate against the venous flow from the GI tract to the liver
eggs are released into the veins
impact of schistosome eggs being released into liver veins
elicit granulomatous inflammatory response
T helper cell response to schistosome eggs
early stage - Th1 profile directed at schistosomula
Th2 response then takes over against egg antigens
granulomatous response to schistosome eggs
granulomas surround eggs
recruit eosinophils, IgE, Th2
characteristics of schistomiasis shown
granulomas then translocated to the intestinal lumen and then excreted
what happens when granulomas dissipate
collagenous scars coalesce and cirrhosis develops
blood bypass channels (varices) form and bleed to cause death
what are protozoa
class of parasite unicellular
why are protozoa good at chronic infections
they have lots of evolutionary adaptations
why is antigenic variation important
underlies capacity of organisms to survive in a host
how are the two groups of protozoal infections introduced
- by bites or tissue injury
2. by ingestion of contaminated water
trypanosoma cruzi
protozoa that causes mega colon
kissing beetles penetrate skin and take blood meal to infect body
what causes african sleeping sickeness
protozoa parasite
trypansoma brusei
VATs
variable antigen type
how does antigenic variation allow escape from host defences
successive dominance of each series of a variable antigen type (VAT) over time
VATs cause appearance of remission in trypansosomes
antibodies destroy homologous trypanosomes
almost successful clearance
parasites then express new VSG thus becoming a new VAT and multiply
VSG
variant-specific surface glycoprotein
VSG release
VSG is released through flagellar resevoir and covers parasite as a surface coat
where are VSG expression sites
at the ends of chromosomes
role of syk
adaptor protein for dectin-1 (PRR)
enhances signalling
