Transcript Protozoan Diseases

Protozoan Diseases
• Protozoans are unicellular eukaryotic organisms
• Responsible for several serious human diseases:
ameobiasis, Chaga’s disease, malaria, African
sleeping sickness, leishmaniasis, and taxoplasmosis.
• Type of immune response that develops depends (in
part) on the location of the parasite in the host.
• Bloodstream: humoral antibody most effective
• Intracellular: cell-mediated immune reactions
Got Malaria?
Plasmodium
• Carried by the Anopheles
mosquito
• P. falciparum– most virulent
and prevalent
• Rate of multi-drug
resistance in Plasmodium
as well as resistance to
DDT by the mosquito
increase the spread of
malaria and call for new
strategies.
•http://www.rph.wa.gov.au/labs/haem/malaria/history.html
•http://www.cdc.gov/travel/malinfo.htm
Malaria. . .
Plasmodium life cycle
• ♀ Anopheles mosquito feeds on
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blood & serves as the vector.
Sporozites enter blood stream and
proceed to the liver within 30 min
to infect hepatocytes
• Circumsporozite (CS), 45kDa protein helps with
adhesion to liver cells. The
binding site, a conserved
region on the carboxyl
terminal end (reg II) has a
high degree of sequence
homology with known cell
adhesion molecules.
http://www.who.int/inf-fs/en/1InformationSheet03.pdf
Malaria. . .
• 1 week = Multiplication &
transformation in the liver leads to the
release of about 5,000-10,000
merozites PER HEPATOCYTE infected
with only one sporozite!
• Merozites infect red blood cells,
initiating the symptoms and pathology
of malaria.
• Merozites replicate and differentiate
again
• Cell ruptures to release new merozites
(which will infect more red blood cells)
• Some merozites differentiate into ♂
and ♀ gametocytes.
• Gametocytes ingested by Female
Anopheles differentiate into male and
female gametes which fuse to form a
zygote and become sporozites in the
salivary gland….
• Wash, Rinse, Repeat…
Malaria. . .
• Chills, fever, sweating—peak
every 48hrs
• Weak, anemic, splenomegaly
• Blocked capillaries = intense
headaches, renal failure, heart
failure, or cerebral damage
• Some symptoms may not be
caused by Plasmodium but by
excessive production of
cytokines
– Cancer patients treated with
recombinant TNF show similar
symptoms
Immune Response to Malaria
• Where malaria is endemic, IR
is poor. Children < 14yrs have
lowest IR and are most likely
to develop malaria. Mortality
rate 50% in some regions;
about 1million children a year
die of malaria.
• Only 22% of children in
endemic regions have
detectable antibodies to the
sporozite stage, 84% of adults
have such antibodies.
• Most people in endemic
regions have life long low-level
Plamsmodium infections.
Malaria in the placenta
Low-Level Immune Response. . .
• Changes from sporozite to merozoite to
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gametocyte allow for changing of surface
molecules. So, antigens seen by immune system
are continually different.
Intracellular phases (hepatocytes &
erythrocytes) reduce the degree of immune
activation. Plasmodium is allowed to multiply
while shielded from attack.
Sporozite stage, most susceptible to IR
circulates for only 30 min.
Plasmodium can slough off surface CS Ag coat,
rendering Ab ineffective.
Malaria Vaccine?
• Current approaches focus on sporozite
stage. (Eg: Sporozites attenuated by xrays used for vaccine)
• Impractical. Sporozites do not breed well
in culture, so mosquito populations need
to be bred.
Yeah, lets breed mosquitoes. Great idea…
African sleeping sickness…ZZZZzzzz
Trypanosoma
• Flagellated protozoans—2
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species
TseTse fly carries
Stages:
– Systemic: multiplies in
blood
– Progresses to neurological
stage, infects central
nervous system
→ meningoencephalitis
(big word, must be bad…)
– Loss of consciousness.
Hence, the SLEEP part.
http://www.biosci.ohio-state.edu/~parasite/lifecycles/trypanosoma_lifecycle.html
AFS Immune Response
• Humoral response to
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glycoprotein coat (variant
surface glycoprotein VSG)
Most of the parasite is
eliminated from the blood…
BUT, 1% escape (because
they’re wearing a different
coat)…all hell breaks loose!
Survivors proliferate and a new
wave of parasitemia is
observed.
Antigenic shift allows
trypanosomes to evade
immune system
Each new variant can escape
humoral Ab generated for the
preceeding variant.
Sneaky sneaky. . .
Variation in VSG
• Trypanosomes carry a
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HUUUGE number of VSG genes
Activation of VSG gene=
duplication & transposition to
expression site at the telomeric
end of a specific chromosome
Activation of new gene
displaces previous gene
Each new variant arises from
the growth of multiple cells
that have activated the same
VSG gene in the current wave.
Continual shifts in the epitope
displayed by the VSG make
vaccine development difficult.
Leishmaniasis
Leishmania major
• Lives in the phagosomes of
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macrophages
Resistence correlates with IFNγ and development of TH 1
response.
Loss of IFN-γ or IFN-γ receptor
= fatality
BALB/c mice mount TH 2
response = high IL-4 but no
IFN-γ
BALB/c CD4+ Tcells can see a
particular epitope on L.major
and produce high IL-4 early in
the response. This skews the
response to
TH 2 and the mice die……
SAY CHEESE!!!
Leishmania Ulcer
Parasitic Worms…
mmm mmm good
Helminths
• Large, multicellular organisms
• Reside in humans, but do not usually
replicate there
• NOT intracellular
• Most infected individuals carry few,
immune system not heavily engaged, level
of immunity generated is often poor
A Plethora of Disease…
• >1 billion have Ascaris, a roundworm in the
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small intestine
>300 million infected with Schistosoma,
trematode worm causing debilitating infection
Taenia—tapeworm of cattle and pigs
Trichinella—roundworm of pigs causing
Trichinosis
…just to name a few
Ascaris
Taenia
Schistosomiasis
3 major species:
– S. mansoni (intestinal
mesenteric veins)
– S. japonicum (intestinal
mesenteric veins)
– S. haematobium (urinary
bladder veins)
Africa, Middle East, S. America,
Caribbean,
China, S.E. Asia
*Increase in irrigation has expanded
the habitat of the fresh water
snail, the intermediate host.
Attack of the Killer Snails!!!
• Snails release 300-3000
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cercariae (free swimming
larvae)
Cercariae secrete
digestive enzymes and
bore into skin
– Lose tail → schistosomules
– Enter cappillaries → lungs
→ liver →main infection
site (depending on species)
– Mature into ♀and ♂ worms
→ mate
– ♀produces 300 spiny
eggs/day
Attack of the Killer Snails!!!
• Eggs do not mature—some get into feces
& urine where, upon excretion, they infect
more snails
• # of worms in the individual increases
only with repeated exposure
• Most symptoms initiated by the eggs…
SYPMTOMS
• ½ the eggs can remain: invade intestinal
wall, liver, or bladder → hemorrhage
• Unexcreted eggs induce cell-mediated
delayed type hypersensitvity. Large
granulomas are formed and walled off by
fibrous tissue
• Granulomas often obstruct venous blood
flow to the liver or bladder.
Immune Response
• No IR to Schistomosomes; survive for up
to 20 years evading attack of localized
cellular buildup of immune and
inflammatory cells
• Several mechanisms of defense: decrease
Ag expression, Cover in glycolipid/protein
coat from the host → host’s own ABO
blood group antigens are on the worm’s
body along with histocompatibility
antigens
For All You Hypochondriacs
Possible signs and symptoms of internal parasites:
• Feel tired most of the time (Chronic Fatigue)?
• Have digestive problems? (gas, bloating, constipation or diarrhea that come and go but never really
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clear up)
Have gastrointestinal symptoms and bulky stools with excess fat in feces?
Suffer with food sensitivities and environmental intolerance?
Developed allergic-like reactions and can’t understand why?
Have joint and muscle pains and inflammation often assumed to be arthritis?
Suffer with anemia or iron deficiency (pernicious anemia)?
Have hives, rashes, weeping eczema, cutaneous ulcers, swelling, sores, papular lesions, itchy
dermatitis?
Suffer with restlessness and anxiety?
Experience multiple awakenings during the night particularly between 2 and 3 am?
Grind your teeth?
Have an excessive amount of bacterial or viral infections?
Depressed?
Difficulty gaining or losing weight no matter what you do?
Did a Candida program which either didn’t help at all or helped somewhat but you still can’t stay away
from bread, alcohol, fruit, or fruit juices?
Just can’t figure out why you don’t feel really great and neither can your doctor? These are only possible
itchy ears, nose, anus
symptoms, and please keep in
forgetfulness, slow reflexes, gas and bloating, unclear thinking;
mind that not everyone that
loss of appetite, yellowish face
fast heartbeat, heart pain, pain in the navel;
has a few of these symptoms
eating more than normal but still feeling hungry;
should automatically make the
pain in the back, thighs, shoulders;
assumption that they are
lethargy;
numb hands;
infected; however, if you
burning sensation in the stomach;
suspect infection or have been
drooling while sleeping;
unsuccessfully treated for a
damp lips at night, dry lips during the day, grinding teeth while asleep;
bed wetting;
problem, it is worth doing some
women: problems with the menstrual cycle;
specific parasite cleansing.
men: sexual dysfunction;
For your enjoyment. . .
And because I’m supposed to be
writing a term paper
• http://www.curezone.com/diseases/parasites/default.asp
WARNING: The following images are
graphic and offensive in nature. They are
unnecessary but really cool. Please take
care and remove children from the room.