Protozoan Diseases

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Protozoan Diseases

• Protozoans are unicellular eukaryotic organisms
• Responsible for several serious human diseases
  ameobiasis, Chagas 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

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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

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Malaria. . .

• Plasmodium life cycle
• ? Anopheles mosquito feeds on blood serves as
  the vector.
• Sporozites enter blood stream and proceed to the
  liver within 30 min to infect hepatocytes
• Circumsporozite (CS), 45-kDa 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.p
df
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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

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Malaria. . .

• Chills, fever, sweatingpeak 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

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Immune Response to Malaria

• Where malaria is endemic, IR is poor. Children lt
  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
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Low-Level Immune Response. . .

• Changes from sporozite to merozoite to 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.

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Malaria Vaccine?

• Current approaches focus on sporozite stage.
  (Eg Sporozites attenuated by x-rays used for
  vaccine)
• Impractical. Sporozites do not breed well in
  culture, so mosquito populations need to be bred.
• Yeah, lets breed mosquitoes. Great idea

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African sleeping sicknessZZZZzzzz

• Trypanosoma
• Flagellated protozoans2 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/lifecyc
les/trypanosoma_lifecycle.html
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AFS Immune Response

• Humoral response to glycoprotein coat (variant
  surface glycoprotein VSG)
• Most of the parasite is eliminated from the
  blood
• BUT, 1 escape (because theyre 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.

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Sneaky sneaky. . .

• Variation in VSG
• Trypanosomes carry a 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.

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Leishmaniasis

• Leishmania major
• Lives in the phagosomes of macrophages
• Resistence correlates with IFN-? and development
  of TH 1 response.
• Loss of IFN-? or IFN-? receptor fatality
• BALB/c mice mount TH 2 response high IL-4 but
  no IFN-?
• 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

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SAY CHEESE!!!
Leishmania Ulcer
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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

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A Plethora of Disease

• gt1 billion have Ascaris, a roundworm in the small
  intestine
• gt300 million infected with Schistosoma, trematode
  worm causing debilitating infection
• Taeniatapeworm of cattle and pigs
• Trichinellaroundworm of pigs causing Trichinosis
  
• just to name a few

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Ascaris
Taenia
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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.

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Attack of the Killer Snails!!!

• Snails release 300-3000 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

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Attack of the Killer Snails!!!

• Eggs do not maturesome 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

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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.

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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 ? hosts own ABO blood group antigens
  are on the worms body along with
  histocompatibility antigens

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• 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 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 cant
  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 didnt help at
  all or helped somewhat but you still cant stay
  away from bread, alcohol, fruit, or fruit juices?
  
• Just cant figure out why you dont feel really
  great and neither can your doctor?

These are only possible symptoms, and please keep
in mind that not everyone that has a few of these
symptoms should automatically make the assumption
that they are infected however, if you suspect
infection or have been unsuccessfully treated for
a problem, it is worth doing some specific
parasite cleansing.
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For your enjoyment. . .And because Im
supposed to be writing a term paper

• http//www.curezone.com/diseases/parasites/default
  .asp

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• 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.

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