Lecture3 medical important the Protozoa.ppt

Protozoans
Protozoans
 Protozoans include a wide diversity of taxa that do
Protozoans include a wide diversity of taxa that do
not form a monophyletic group but all are
not form a monophyletic group but all are
unicellular eukaryotes.
unicellular eukaryotes.
 Protozoa lack a cell wall, have at least one motile
Protozoa lack a cell wall, have at least one motile
stage in their life cycle and most ingest their food.
stage in their life cycle and most ingest their food.
 Protozoan cell is much larger and more complex
Protozoan cell is much larger and more complex
than prokaryotic cell and contains a variety of
than prokaryotic cell and contains a variety of
organelles (e.g. Golgi apparatus, mitochondria,
organelles (e.g. Golgi apparatus, mitochondria,
ribosomes, etc).
ribosomes, etc).

Protozoans
Protozoans
 Eukaryotic cell was developed through endosymbiosis.
Eukaryotic cell was developed through endosymbiosis.
 In distant past aerobic bacteria appear to have been
In distant past aerobic bacteria appear to have been
engulfed by anaerobic bacteria, but not digested.
engulfed by anaerobic bacteria, but not digested.
Ultimately, the two developed a symbiotic relationship
Ultimately, the two developed a symbiotic relationship
with the engulfed aerobic bacteria becoming
with the engulfed aerobic bacteria becoming
mitochondria and eukaryotic cells developed.
mitochondria and eukaryotic cells developed.
 In a similar fashion, ancestors of chloroplasts formed
In a similar fashion, ancestors of chloroplasts formed
symbiotic union with other prokaryotes.
symbiotic union with other prokaryotes.

Protozoans
Protozoans
 Protozoans include both autotrophs and
Protozoans include both autotrophs and
heterotrophs. They include free-living and
heterotrophs. They include free-living and
parasitic forms.
parasitic forms.
 Reproduction can be asexual by fission or
Reproduction can be asexual by fission or
budding or sexual by conjugation or
budding or sexual by conjugation or
syngamy (fusion of gametes).
syngamy (fusion of gametes).

Protozoans
Protozoans
 The protozoa were once considered a
The protozoa were once considered a
single phylum, now at least 7 phyla are
single phylum, now at least 7 phyla are
recognized.
recognized.
 Were also once grouped with unicellular
Were also once grouped with unicellular
algae into the Protista, an even larger
algae into the Protista, an even larger
paraphyletic group.
paraphyletic group.

Movement in Protozoa
Movement in Protozoa
 Protozoa move mainly using cilia or
Protozoa move mainly using cilia or
flagella and by using pseudopodia
flagella and by using pseudopodia
 Cilia also used for feeding in many small
Cilia also used for feeding in many small
metazoans.
metazoans.

Cilia and flagella
Cilia and flagella
 No real morphological distinction between
No real morphological distinction between
the two structures, but cilia are usually
the two structures, but cilia are usually
shorter and more abundant and flagella
shorter and more abundant and flagella
fewer and longer.
fewer and longer.
 Each flagellum or cilium is composed of 9
Each flagellum or cilium is composed of 9
pairs of longitudinal microtubules arranged
pairs of longitudinal microtubules arranged
in a circle around a central pair.
in a circle around a central pair.

Cilia and flagella
Cilia and flagella
 The collection of tubules is referred to as
The collection of tubules is referred to as
the
the axoneme
axoneme and it is covered with a
and it is covered with a
membrane continuous with the rest of the
membrane continuous with the rest of the
organism’s cell membrane.
organism’s cell membrane.
 Axoneme anchors where it inserts into the
Axoneme anchors where it inserts into the
main body of the cell with a basal body.
main body of the cell with a basal body.

Figure 11.09a
Figure 11.09a
Protein spoke
Dynein motor
Basal body

Cilia and flagella
Cilia and flagella
 The outer microtubules are connected to
The outer microtubules are connected to
the central pair by protein spokes.
the central pair by protein spokes.
 Neighboring pairs of outer microtubules
Neighboring pairs of outer microtubules
(doublets) are connected to each other by
(doublets) are connected to each other by
an elastic protein.
an elastic protein.

Figure 11.09a
Figure 11.09a
Protein spoke
Dynein motor

Cilia and flagella
Cilia and flagella
 Cilium is powered by dynein motors on the outer
Cilium is powered by dynein motors on the outer
doublets. As these motors crawl up the adjacent
doublets. As these motors crawl up the adjacent
doublet (movement is powered by ATP) they
doublet (movement is powered by ATP) they
cause the entire axoneme to bend.
cause the entire axoneme to bend.
 The dynein motors do not cause the doublets to
The dynein motors do not cause the doublets to
slide past each other because the doublets are
slide past each other because the doublets are
attached to each other by the elastic proteins
attached to each other by the elastic proteins
and the radial spokes and have little freedom of
and the radial spokes and have little freedom of
movement up and down. Instead the walking
movement up and down. Instead the walking
motion causes the doublets to bend.
motion causes the doublets to bend.

Flagella, “intelligent design” and
irreducible complexity
 Oddly, the humble flagellum has been
Oddly, the humble flagellum has been
dragged into the evolution culture wars!
dragged into the evolution culture wars!

 The U.S. Supreme Court has prohibited
The U.S. Supreme Court has prohibited
the teaching of creationism in public
the teaching of creationism in public
schools as a violation of the
schools as a violation of the
“establishment of religion” clause of the
“establishment of religion” clause of the
constitution.
constitution.
 Latest attempt to insert creationism into
Latest attempt to insert creationism into
schools is the idea of “Intelligent Design.”
schools is the idea of “Intelligent Design.”

 The concept of “intelligent design” is outlined
The concept of “intelligent design” is outlined
most clearly in Michael Behe’s book “Darwin’s
most clearly in Michael Behe’s book “Darwin’s
Black Box.”
Black Box.”
 The central idea in “intelligent design” is that
The central idea in “intelligent design” is that
some structures in the body are so complex that
some structures in the body are so complex that
they could not possibly have evolved by a
they could not possibly have evolved by a
gradual process of natural selection. These
gradual process of natural selection. These
structures are said to “irreducibly complex.”
structures are said to “irreducibly complex.”

 By “irreducibly complex” Behe means that
By “irreducibly complex” Behe means that
a complex structure cannot be broken
a complex structure cannot be broken
down into components that are
down into components that are
themselves functional and that the
themselves functional and that the
structure must have come into existence in
structure must have come into existence in
its complete form.
its complete form.

 If structures are “irreducibly complex”
If structures are “irreducibly complex”
Behe claims that they cannot have
Behe claims that they cannot have
evolved.
evolved.
 Thus, their existence implies they must
Thus, their existence implies they must
have been created by a designer (i.e. God,
have been created by a designer (i.e. God,
although the designer is not explicitly
although the designer is not explicitly
referred to as such).
referred to as such).

 One of Behe’s main examples is flagella/cilia.
One of Behe’s main examples is flagella/cilia.
 Behe claims that because cilia are composed of
Behe claims that because cilia are composed of
at least half a dozen proteins, which combine to
at least half a dozen proteins, which combine to
perform one task, and that all of the proteins
perform one task, and that all of the proteins
must be present for a cilium to work and that
must be present for a cilium to work and that
cilia could not have evolved in a step-by step
cilia could not have evolved in a step-by step
process of gradual improvement.
process of gradual improvement.

 The flagellum is not, in fact, irreducibly complex.
The flagellum is not, in fact, irreducibly complex.
 For example, the flagellum in eel sperm lacks
For example, the flagellum in eel sperm lacks
several of the components found in other flagella
several of the components found in other flagella
(including the central pair of microtubules, radial
(including the central pair of microtubules, radial
spokes, and outer row of dynein motors), yet the
spokes, and outer row of dynein motors), yet the
flagellum functions well.
flagellum functions well.

 The whole “irreducible complexity”
The whole “irreducible complexity”
argument could in reality be recast as an
argument could in reality be recast as an
argument of “personal incredulity.”
argument of “personal incredulity.”
 “
“I personally cannot imagine a sequence
I personally cannot imagine a sequence
of steps by which this complex structure
of steps by which this complex structure
could have evolved. Therefore, it must
could have evolved. Therefore, it must
have been created.”
have been created.”

Movement in Protozoa:
Movement in Protozoa:
Pseudopodia
Pseudopodia
 Pseudopodia are chief means of
Pseudopodia are chief means of
locomotion of amoebas but are also
locomotion of amoebas but are also
formed by other protozoa and amoeboid
formed by other protozoa and amoeboid
cells of many invertebrates.
cells of many invertebrates.
 In amoeboid movement the organism
In amoeboid movement the organism
extends a pseudopodium in the direction it
extends a pseudopodium in the direction it
wishes to travel and then flows into it.
wishes to travel and then flows into it.

Pseudopodia
Pseudopodia
 Amoeboid movement involves endoplasm and
Amoeboid movement involves endoplasm and
ectoplasm. Endoplasm is more fluid than
ectoplasm. Endoplasm is more fluid than
ectoplasm which is gel-like.
ectoplasm which is gel-like.
 When a pseudopodium forms, an extension of
When a pseudopodium forms, an extension of
ectoplasm (the hyaline cap) appears and
ectoplasm (the hyaline cap) appears and
endoplasm flows into it and fountains to the
endoplasm flows into it and fountains to the
periphery where it becomes ectoplasm. Thus, a
periphery where it becomes ectoplasm. Thus, a
tube of ectoplasm forms that the endoplasm
tube of ectoplasm forms that the endoplasm
flows through. The pseudopodium anchors to
flows through. The pseudopodium anchors to
the substrate and the organism moves forward.
the substrate and the organism moves forward.

Feeding in amebas
Feeding in amebas
 Feeding in amoebas involves using
Feeding in amoebas involves using
pseudpodia to surround and engulf a
pseudpodia to surround and engulf a
particle in the process of
particle in the process of phagocytosis
phagocytosis.
.
 The particle is surrounded and a food
The particle is surrounded and a food
vacuole forms into which digestive
vacuole forms into which digestive
enzymes are poured and the digested
enzymes are poured and the digested
remains are absorbed across the cell
remains are absorbed across the cell
membrane.
membrane.

Reproduction in protozoa
Reproduction in protozoa
 The commonest form of reproduction is
The commonest form of reproduction is
binary fission
binary fission in which two essentially
in which two essentially
identical individuals result.
identical individuals result.
 In some ciliates
In some ciliates budding
budding occurs in which
occurs in which
a smaller progeny cell is budded off which
a smaller progeny cell is budded off which
later grows to adult size.
later grows to adult size.

Binary fission
in various taxa

Sexual reproduction in protozoa
Sexual reproduction in protozoa
 All protozoa reproduce asexually, but sex
All protozoa reproduce asexually, but sex
is widespread in the protozoa too.
is widespread in the protozoa too.
 In ciliates such as
In ciliates such as Paramecium,
Paramecium, a type of
a type of
sexual reproduction called conjugation
sexual reproduction called conjugation
takes place in which two Paramecia join
takes place in which two Paramecia join
together and exchange genetic material
together and exchange genetic material

Diseases caused by protozoa
Diseases caused by protozoa
 Many diseases are caused by protozaon
Many diseases are caused by protozaon
parasites
parasites
 These include:
These include:
 Malaria (caused by a sporozaon)
Malaria (caused by a sporozaon)
 Giardia, Sleeping sickness (caused by
Giardia, Sleeping sickness (caused by
flagellates)
flagellates)
 Amoebic dysentry (caused by amoebae)
Amoebic dysentry (caused by amoebae)

Malaria
Malaria
 Malaria is one of the most important diseases in the
Malaria is one of the most important diseases in the
world.
world.
 About 500 million cases and an estimated 700,000 to
About 500 million cases and an estimated 700,000 to
2.7 million deaths occur worldwide each year (CDC).
2.7 million deaths occur worldwide each year (CDC).
 Malaria was well known to the Ancient Greeks and
Malaria was well known to the Ancient Greeks and
Romans. The Romans thought the disease was caused
Romans. The Romans thought the disease was caused
by bad air (in Latin
by bad air (in Latin mal-aria
mal-aria) from swamps, which they
) from swamps, which they
drained to prevent the disease.
drained to prevent the disease.

Malaria symptoms
Malaria symptoms
 The severity of an infection may range from
The severity of an infection may range from
asymptomatic (no apparent sign of illness) to the
asymptomatic (no apparent sign of illness) to the
classic symptoms of malaria (fever, chills,
classic symptoms of malaria (fever, chills,
sweating, headaches, muscle pains), to severe
sweating, headaches, muscle pains), to severe
complications (cerebral malaria, anemia, kidney
complications (cerebral malaria, anemia, kidney
failure) that can result in death.
failure) that can result in death.
 Factors such as the species of
Factors such as the species of Plasmodium
Plasmodium and
and
the victims genetic background and acquired
the victims genetic background and acquired
immunity affect the severity of symptoms.
immunity affect the severity of symptoms.

Malaria
Malaria
 Despite humans long history with malaria
Despite humans long history with malaria
its cause, a sporozoan parasite called
its cause, a sporozoan parasite called
Plasmodium,
Plasmodium, was not discovered until
was not discovered until
1889 when Charles Louis Alphonse
1889 when Charles Louis Alphonse
Laveran a French army physician
Laveran a French army physician
identified it, a discovery for which he won
identified it, a discovery for which he won
the Nobel Prize in 1907.
the Nobel Prize in 1907.

Malaria
Malaria
 In 1897 an equally important discovery,
In 1897 an equally important discovery,
the mode of transmission of malaria, was
the mode of transmission of malaria, was
made by Ronald Ross.
made by Ronald Ross.
 His identification of the
His identification of the Anopheles
Anopheles
mosquito as the transmitting agent earned
mosquito as the transmitting agent earned
him the 1902 Nobel Prize and a
him the 1902 Nobel Prize and a
knighthood in 1911.
knighthood in 1911.

Plasmodium
Plasmodium
 There are four species of
There are four species of Plasmodium
Plasmodium:
: P.
P.
falciparum, P. vivax, P.ovale
falciparum, P. vivax, P.ovale and
and P.
P.
malariae.
malariae.
 P. falciparum
P. falciparum causes severe often fatal
causes severe often fatal
malaria and is responsible for most
malaria and is responsible for most
deaths, with most victims being children.
deaths, with most victims being children.

Plasmodium
Plasmodium
 Both
Both Plasmodium vivax
Plasmodium vivax and
and P. ovale
P. ovale can go
can go
dormant, hiding out in the liver. The parasites
dormant, hiding out in the liver. The parasites
can reactivate and cause malaria months or
can reactivate and cause malaria months or
years after the initial infection.
years after the initial infection.
 P. malariae
P. malariae causes a long-lasting infection. If
causes a long-lasting infection. If
the infection is untreated it can persist
the infection is untreated it can persist
asymptomatically for the lifetime of the host.
asymptomatically for the lifetime of the host.

Life cycle of malaria
Life cycle of malaria
 Plasmodium
Plasmodium has two hosts: mosquitoes
has two hosts: mosquitoes
and humans.
and humans.
 Sexual reproduction takes place in the
Sexual reproduction takes place in the
mosquito and the parasite is transmitted to
mosquito and the parasite is transmitted to
humans when the mosquito takes a blood
humans when the mosquito takes a blood
meal.
meal.

Life cycle of malaria: humans
Life cycle of malaria: humans
 The mosquito injects
The mosquito injects Plasmodium
Plasmodium into a human in the
into a human in the
form of
form of sporozoites
sporozoites.
.
 The sporozoites first invade liver cells and asexually
The sporozoites first invade liver cells and asexually
reproduce to produce huge numbers of
reproduce to produce huge numbers of merozoites
merozoites
which spread to red blood cells where more merozoites
which spread to red blood cells where more merozoites
are produced through more asexual reproduction.
are produced through more asexual reproduction.
 Some parasites transform into sexually reproducing
Some parasites transform into sexually reproducing
gametocytes
gametocytes and these if ingested by a mosquito
and these if ingested by a mosquito
continue the cycle.
continue the cycle.

Life cycle of malaria: mosquitoes
Life cycle of malaria: mosquitoes
 Gametocytes ingested by a mosquito combine in
Gametocytes ingested by a mosquito combine in
the mosquito’s stomach to produce zygotes.
the mosquito’s stomach to produce zygotes.
 These zygotes develop into motile elongated
These zygotes develop into motile elongated
ookinites
ookinites.
.
 The ookinites invade the mosquito’s midgut wall
The ookinites invade the mosquito’s midgut wall
where they ultimately produce sporozoites,
where they ultimately produce sporozoites,
which make their way to the salivary glands
which make their way to the salivary glands
where they can be injected into a new human
where they can be injected into a new human
host.
host.

How
How Plasmodium
Plasmodium enhances
enhances
transmission rates
transmission rates
 The
The Plasmodium
Plasmodium parasite engages in a
parasite engages in a
number of manipulative behaviors to
number of manipulative behaviors to
enhance its chances of being transmitted
enhance its chances of being transmitted
between hosts.
between hosts.
 Such manipulations are a common feature
Such manipulations are a common feature
of parasite behavior, in general, as we will
of parasite behavior, in general, as we will
see throughout the semester.
see throughout the semester.

How
How Plasmodium
Plasmodium enhances
enhances
transmission rates
transmission rates
 Mosquitoes risk death when feeding and
Mosquitoes risk death when feeding and
attempt to minimize risk and maximize
attempt to minimize risk and maximize
reward when doing so.
reward when doing so.
 To obtain blood a mosquito must insert its
To obtain blood a mosquito must insert its
proboscis through the skin and then locate
proboscis through the skin and then locate
a blood vessel. The longer this takes, the
a blood vessel. The longer this takes, the
greater the risk.
greater the risk.

How
How Plasmodium
Plasmodium enhances
enhances
transmission rates
transmission rates
 As soon as the mosquito hits a blood
As soon as the mosquito hits a blood
vessel the host’s body responds by
vessel the host’s body responds by
clotting the wound.
clotting the wound.
 Platelets clump around the proboscis and
Platelets clump around the proboscis and
release chemicals which cause the
release chemicals which cause the
platelets to clot together.
platelets to clot together.

How
How Plasmodium
Plasmodium enhances
enhances
transmission rates
transmission rates
 To slow clotting and speed feeding, mosquitoes
To slow clotting and speed feeding, mosquitoes
inject anticoagulants including one called
inject anticoagulants including one called
apyrase that unglues the platelets. They also
apyrase that unglues the platelets. They also
inject other chemicals that expand the blood
inject other chemicals that expand the blood
vessels.
vessels.
 Plasmodium
Plasmodium in the host helps the mosquito feed
in the host helps the mosquito feed
by releasing chemicals that also slow clotting.
by releasing chemicals that also slow clotting.
The parasite’s help increases the chances of the
The parasite’s help increases the chances of the
mosquito feeding successfully and sucking up
mosquito feeding successfully and sucking up
the parasite.
the parasite.

How
How Plasmodium
Plasmodium enhances
enhances
transmission rates
transmission rates
 Once in the mosquito
Once in the mosquito Plasmodium
Plasmodium needs about
needs about
10 days to produce sporozoites that are ready to
10 days to produce sporozoites that are ready to
be injected into a human.
be injected into a human.
 During this time, to reduce the chances of the
During this time, to reduce the chances of the
mosquito dying,
mosquito dying, Plasmodium
Plasmodium apparently
apparently
discourages its host from eating. Although how
discourages its host from eating. Although how
the parasite does this is not clear, mosquitoes
the parasite does this is not clear, mosquitoes
containing ookinites abandon feeding attempts
containing ookinites abandon feeding attempts
sooner than parasite-free mosquitoes.
sooner than parasite-free mosquitoes.

How
How Plasmodium
Plasmodium enhances
enhances
transmission rates
transmission rates
 Once sporozoites are in the salivary
Once sporozoites are in the salivary
glands, however,
glands, however, Plasmodium
Plasmodium wants the
wants the
mosquito to bite and bite often.
mosquito to bite and bite often.
 In the salivary gland the parasite cuts off
In the salivary gland the parasite cuts off
the mosquito’s anticoagulant apyrase
the mosquito’s anticoagulant apyrase
supply. This makes it harder for the
supply. This makes it harder for the
mosquito to feed so it is hungrier and bites
mosquito to feed so it is hungrier and bites
more hosts.
more hosts.

How
How Plasmodium
Plasmodium enhances
enhances
transmission rates
transmission rates
 As a result, an infected mosquito is twice
As a result, an infected mosquito is twice
as likely to bite two people in a single night
as likely to bite two people in a single night
as an uninfected mosquito is.
as an uninfected mosquito is.
 As a result, the parasite is spread more
As a result, the parasite is spread more
widely.
widely.

Behavior of
Behavior of Plasmodium
Plasmodium in humans
in humans
 Plasmodium
Plasmodium enters the blood stream through a
enters the blood stream through a
mosquito bite.
mosquito bite.
 The parasite must avoid the host’s immune
The parasite must avoid the host’s immune
system. To do so while in the body it moves
system. To do so while in the body it moves
from one hiding place to another.
from one hiding place to another.
 The parasite moves first to the liver. Can get
The parasite moves first to the liver. Can get
there in about 30 minutes, which is usually fast
there in about 30 minutes, which is usually fast
enough to avoid triggering the immune system.
enough to avoid triggering the immune system.

Behavior of
in humans
 At the liver
At the liver Plasmodium
Plasmodium enters a liver cell.
enters a liver cell.
 The cell responds by grabbing
The cell responds by grabbing
Plasmodium
Plasmodium proteins and displaying the
proteins and displaying the
antigens on its cell surface in a special cup
antigens on its cell surface in a special cup
the major histocompatibility complex or
the major histocompatibility complex or
MHC.
MHC.

Behavior of
in humans
 The immune system recognizes the
The immune system recognizes the
Plasmodium
Plasmodium antigens and mounts an
antigens and mounts an
immune response.
immune response.
 However, in a week before the immune
However, in a week before the immune
system has mounted its full response the
system has mounted its full response the
parasite has produced about 40,000
parasite has produced about 40,000
copies of itself and these burst out of the
copies of itself and these burst out of the
liver to seek red blood cells.
liver to seek red blood cells.

Behavior of
in humans
 The parasites leave the liver, reenter the
The parasites leave the liver, reenter the
bloodstream, and find a red blood cell to
bloodstream, and find a red blood cell to
enter.
enter.
 Each parasite spends two days in a red
Each parasite spends two days in a red
blood cell consuming the hemoglobin and
blood cell consuming the hemoglobin and
reproducing.
reproducing.

Red blood cells
Red blood cells
 Red blood cells (strictly red blood
Red blood cells (strictly red blood
corpuscles) are a challenging environment
corpuscles) are a challenging environment
to live in.
to live in.
 They lack a nucleus and have little
They lack a nucleus and have little
metabolic activity. As a result, they have
metabolic activity. As a result, they have
few proteins for generating energy and
few proteins for generating energy and
also lack most of a normal cell’s channels
also lack most of a normal cell’s channels
for transporting fuel in and wastes out.
for transporting fuel in and wastes out.

Red blood cells
Red blood cells
 Red blood cells are specialized to
Red blood cells are specialized to
transport oxygen, which they carry by
transport oxygen, which they carry by
binding and wrapping in hemoglobin
binding and wrapping in hemoglobin
molecules.
molecules.
 A red blood cell is pumped around the
A red blood cell is pumped around the
body by the heart and travels about 300
body by the heart and travels about 300
miles over its lifetime.
miles over its lifetime.

Red blood cells
Red blood cells
 Red blood cells are squeezed through
Red blood cells are squeezed through
slender capillaries and compressed to one
slender capillaries and compressed to one
fifth of their normal diameter before
fifth of their normal diameter before
rebounding.
rebounding.
 To survive this squeezing, red blood cells
To survive this squeezing, red blood cells
have a network of proteins under their
have a network of proteins under their
membrane that can fold like a concertina
membrane that can fold like a concertina
and allow the cell to stretch and squeeze
and allow the cell to stretch and squeeze
as needed.
as needed.

Red blood cells
Red blood cells
 Old red blood cells eventually lose their
Old red blood cells eventually lose their
elasticity and become stiff.
elasticity and become stiff.
 Those that show signs of such aging are
Those that show signs of such aging are
filtered out as they pass through the
filtered out as they pass through the
spleen and destroyed.
spleen and destroyed.

Behavior of
in humans
 Plasmodium
Plasmodium cannot swim but uses hooks
cannot swim but uses hooks
to move along the blood vessels.
to move along the blood vessels.
 At the parasite’s tip are sensors that
At the parasite’s tip are sensors that
respond only to young red blood cells and
respond only to young red blood cells and
clasp on to proteins on the cell’s surface.
clasp on to proteins on the cell’s surface.

Behavior of
in humans
 The parasite uses a set of organelles
The parasite uses a set of organelles
concentrated at its apical end to gain
concentrated at its apical end to gain
entry. A suite of proteins are produced
entry. A suite of proteins are produced
that cause the red blood cell’s membrane
that cause the red blood cell’s membrane
to open and let the parasite squeeze in.
to open and let the parasite squeeze in.
 It takes only about 15 seconds for the
It takes only about 15 seconds for the
parasite to get in.
parasite to get in.

Figure 11.30
Plasmodium Sporozoite

Behavior of
in humans
 Inside in the red blood cell the
Inside in the red blood cell the
Plasmodium
Plasmodium consumes the hemoglobin. It
consumes the hemoglobin. It
takes in a small amount of hemoglobin,
takes in a small amount of hemoglobin,
slices it apart with enzymes and harvests
slices it apart with enzymes and harvests
the energy released.
the energy released.
 The toxic core of the hemoglobin molecule
The toxic core of the hemoglobin molecule
is processed into an inert molecule called
is processed into an inert molecule called
hemozoin.
hemozoin.

Behavior of
in humans
 In order to reproduce,
In order to reproduce, Plasmodium
Plasmodium needs more
needs more
than hemoglobin.
than hemoglobin.
 It sets about modifying the red blood corpuscle
It sets about modifying the red blood corpuscle
so it can obtain amino acids and make proteins.
so it can obtain amino acids and make proteins.
 The parasite builds a series of tubes that
The parasite builds a series of tubes that
connect it to the surface of the cell and uses
connect it to the surface of the cell and uses
these to bring in materials from the blood steam
these to bring in materials from the blood steam
and to pump out wastes.
and to pump out wastes.

Behavior of
in humans
 The parasite also produces proteins that help to
The parasite also produces proteins that help to
maintain the red blood cell’s springiness for as
maintain the red blood cell’s springiness for as
long as possible so it is not eliminated by the
long as possible so it is not eliminated by the
spleen.
spleen.
 After a few hours, however, the red blood cell
After a few hours, however, the red blood cell
has been too modified by the parasite to fool the
has been too modified by the parasite to fool the
spleen. The parasite now produces sticky
spleen. The parasite now produces sticky latch
latch
proteins
proteins that glue the cell to blood vessel walls.
that glue the cell to blood vessel walls.

Behavior of
in humans
 Infected cells clump up in capillaries.
Infected cells clump up in capillaries.
 After another day the contents of the cell have
After another day the contents of the cell have
been used up. The cell ruptures and 16 new
been used up. The cell ruptures and 16 new
parasites burst out to infect other red blood cells.
parasites burst out to infect other red blood cells.
 Some of these parasites transform into sexually
Some of these parasites transform into sexually
reproducing gametocytes and, as mentioned
reproducing gametocytes and, as mentioned
previously, these if ingested by a mosquito will
previously, these if ingested by a mosquito will
continue the cycle.
continue the cycle.

Behavior of
in humans
 While in the red blood cells
While in the red blood cells Plasmodium
Plasmodium is
is
invisible to the immune system because
invisible to the immune system because
the red blood cells have no MHC and
the red blood cells have no MHC and
cannot alert the immune system.
cannot alert the immune system.
 The latch proteins however do stimulate
The latch proteins however do stimulate
the immune system.
the immune system.

Behavior of
in humans
 The latch protein is made by a single
The latch protein is made by a single
gene, but
gene, but Plasmodium
Plasmodium has over 100 such
has over 100 such
genes each of which produces a unique
genes each of which produces a unique
latch.
latch.
 In each generation some of the new
In each generation some of the new
parasites switch on a new latch gene and
parasites switch on a new latch gene and
so the immune system is always playing
so the immune system is always playing
catch up.
catch up.

Effects of malaria on human
Effects of malaria on human
evolution
evolution
 The intense selection pressure imposed
The intense selection pressure imposed
by malaria has resulted in a large number
by malaria has resulted in a large number
of mutations that provide protection
of mutations that provide protection
against the parasite being selected for in
against the parasite being selected for in
humans.
humans.
 The best known is sickle cell anemia.
The best known is sickle cell anemia.

Anti-malaria mutations: Sickle cell
anemia
anemia
 Sickle cell anemia is a condition common
Sickle cell anemia is a condition common
in West Africans (and African Americans
in West Africans (and African Americans
of West African ancestry).
of West African ancestry).
 In sickle cell anemia red blood cells are
In sickle cell anemia red blood cells are
sickle shaped as a result of a mutation
sickle shaped as a result of a mutation
which causes hemoglobin chains to stick
which causes hemoglobin chains to stick
together.
together.

anemia
anemia
 People with the sickle cell allele are protected
People with the sickle cell allele are protected
against
against Plasmodium
Plasmodium because their hemoglobin
because their hemoglobin
under low oxygen conditions contracts into
under low oxygen conditions contracts into
needle-shaped clumps.
needle-shaped clumps.
 This contraction not only causes the sickling of
This contraction not only causes the sickling of
the cell, but harms the parasite. Parasites are
the cell, but harms the parasite. Parasites are
impaled on the clumps and the cell loses its
impaled on the clumps and the cell loses its
ability to pump potassium, which the parasite
ability to pump potassium, which the parasite
needs.
needs.

allele
allele
 People with two copies of the sickle cell
People with two copies of the sickle cell
allele usually die young, but heterozygotes
allele usually die young, but heterozygotes
are protected against malaria.
are protected against malaria.
 As a result the geographic distribution of
As a result the geographic distribution of
the allele and malaria in Africa match quite
the allele and malaria in Africa match quite
closely.
closely.

Anti-malaria mutations: (G6PD)
Anti-malaria mutations: (G6PD)
deficiency
deficiency
 Glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase
(G6PD)
(G6PD) deficiency.
deficiency. There are hundreds
There are hundreds
of alleles known and with more than 400
of alleles known and with more than 400
million people affected G6PD deficiency is
million people affected G6PD deficiency is
the commonest enzyme deficiency known.
the commonest enzyme deficiency known.

Anti-malaria mutations:
Thalassemia
Thalassemia
 Geographic distribution suggests it
Geographic distribution suggests it
protects against malaria and
protects against malaria and
epidemiological evidence also supports
epidemiological evidence also supports
this.
this.
 People with G6PD-202A a reduced activity
People with G6PD-202A a reduced activity
variant common in Africa have a
variant common in Africa have a
significantly reduced risk of suffering
significantly reduced risk of suffering
severe malaria.
severe malaria.

Thalassemia
Thalassemia
 Thalassemia: People with thalassemia
Thalassemia: People with thalassemia
make the ingredients of hemoglobin in the
make the ingredients of hemoglobin in the
wrong amounts.
wrong amounts.
 Too many or too few
Too many or too few α
α or ß
or ß hemoglobin
hemoglobin
chains are produced and when they are
chains are produced and when they are
assembled into hemoglobin molecules
assembled into hemoglobin molecules
spare chains are left over.
spare chains are left over.

Other anti-malaria mutations:
Other anti-malaria mutations:
Thalassemia
Thalassemia
 Extra chains clump together and cause major
Extra chains clump together and cause major
problems in the cell. These clumps grab oxygen,
problems in the cell. These clumps grab oxygen,
but don’t enclose it and the oxygen often
but don’t enclose it and the oxygen often
escapes and because it is strongly charged, the
escapes and because it is strongly charged, the
oxygen damages other molecules in the cell.
oxygen damages other molecules in the cell.
 Severe thalassemia is fatal, but mild forms
Severe thalassemia is fatal, but mild forms
protect against malaria because the loose
protect against malaria because the loose
oxygen severely damages the parasite and
oxygen severely damages the parasite and
renders it unable to invade new cells.
renders it unable to invade new cells.

Ovalocytosis
Ovalocytosis
 Ovalocytosis
Ovalocytosis: Occurs in South east Asia and
: Occurs in South east Asia and
has same genetic rules and consequences as
has same genetic rules and consequences as
sickle cell anemia.
sickle cell anemia.
 People with ovalocytosis have blood cell walls
People with ovalocytosis have blood cell walls
that are so rigid they can’t slip through
that are so rigid they can’t slip through
capillaries. The rigid cell walls make it hard for
capillaries. The rigid cell walls make it hard for
the parasite to enter the cell and the cell’s
the parasite to enter the cell and the cell’s
rigidity appears to prevent the parasite pumping
rigidity appears to prevent the parasite pumping
in phosphates and sulphates it needs to survive.
in phosphates and sulphates it needs to survive.

 One major advantage of these various anti-
One major advantage of these various anti-
malarial mutations appears to be that they
malarial mutations appears to be that they
provide a natural vaccination program for
provide a natural vaccination program for
children.
children.
 By slowing the development of the parasite
By slowing the development of the parasite
these mutations give a child’s naïve immune
these mutations give a child’s naïve immune
system time to overcome
system time to overcome Plasmodium’s
Plasmodium’s
attempts to elude the immune system and mount
attempts to elude the immune system and mount
an immune response. Mild cases of malaria
an immune response. Mild cases of malaria
thus immunize children to malaria and allow
thus immunize children to malaria and allow
them to survive to adulthood.
them to survive to adulthood.

Mosquito nets save lives
Mosquito nets save lives
 www.nothingbutnets.net
www.nothingbutnets.net or
or
www.nothingbutnets.org
www.nothingbutnets.org
 $10 gets a net to a family. 100% of your
$10 gets a net to a family. 100% of your
donation goes to purchase and distribute
donation goes to purchase and distribute
nets.
nets.

Human African Trypanosomiasis
Human African Trypanosomiasis
(Sleeping sickness)
(Sleeping sickness)
 Sleeping sickness is a protozoan disease, which
Sleeping sickness is a protozoan disease, which
like malaria is spread by an insect vector, the
like malaria is spread by an insect vector, the
tsetse fly.
tsetse fly.
 The disease is endemic to sub-Saharan Africa
The disease is endemic to sub-Saharan Africa
and an estimated 300,000 people are infected
and an estimated 300,000 people are infected
annually with about 40,000 deaths.
annually with about 40,000 deaths.
 The disease organism is
The disease organism is Trypanosoma
Trypanosoma brucei
brucei.
.

Trypanosoma forms in blood smear from patient with African trypanosomiasis
http://en.wikipedia.org/wiki/File:Trypanosoma_sp._PHIL_613_lores.jpg

Sleeping Sickness
Sleeping Sickness
 Symptoms:
Symptoms:
 Begins with fever, headaches, and joint pains.
Begins with fever, headaches, and joint pains.
 Lymph nodes may swell enormously and parasite numbers
Lymph nodes may swell enormously and parasite numbers
may be incredibly high. Greatly enlarged lymph nodes in
may be incredibly high. Greatly enlarged lymph nodes in
the back of the neck are tell-tale signs of the disease.
the back of the neck are tell-tale signs of the disease.
 If untreated the parasite may cross the blood-brain barrier,
If untreated the parasite may cross the blood-brain barrier,
which causes the characteristic symptoms the disease is
which causes the characteristic symptoms the disease is
named for. The patient becomes confused and the sleep
named for. The patient becomes confused and the sleep
cycle is disturbed with the patient alternating between
cycle is disturbed with the patient alternating between
manic periods and complete lethargy. Progressive mental
manic periods and complete lethargy. Progressive mental
deterioration is followed by coma and death.
deterioration is followed by coma and death.

Sleeping Sickness
Sleeping Sickness
 Trypanosome levels in infected patients show a
Trypanosome levels in infected patients show a
cycle of sharp peaks and valleys in parasite
cycle of sharp peaks and valleys in parasite
numbers of approximately a week in length.
numbers of approximately a week in length.
 The cycle occurs because the immune system
The cycle occurs because the immune system
recognizes the glycoprotein in the trypanosomes
recognizes the glycoprotein in the trypanosomes
coat and mounts an immune response to it,
coat and mounts an immune response to it,
which eliminates parasites with that glycoprotein.
which eliminates parasites with that glycoprotein.

Sleeping Sickness
Sleeping Sickness
 Trypanosomes, however, possess about 1,000
Trypanosomes, however, possess about 1,000
different coat-building genes and periodically a
different coat-building genes and periodically a
new one is turned on by a trypanosome that
new one is turned on by a trypanosome that
produces a different coat, which the immune
produces a different coat, which the immune
system doesn’t recognize.
system doesn’t recognize.
 Trypanosomes with this new coat reproduce
Trypanosomes with this new coat reproduce
undetected until the immune system can mount
undetected until the immune system can mount
a response to the new coat.
a response to the new coat.

Sleeping Sickness
Sleeping Sickness
 If the first generation of trypanosomes to infect a
If the first generation of trypanosomes to infect a
host turned on their coat genes at random the
host turned on their coat genes at random the
immune system could learn to recognize the
immune system could learn to recognize the
various possibilities quickly, remember them,
various possibilities quickly, remember them,
and eliminate the parasite.
and eliminate the parasite.
 Instead the coat-building genes are turned on in
Instead the coat-building genes are turned on in
pre-set sequence.
pre-set sequence. This means that the immune
This means that the immune
system every week or so is faced with a new
system every week or so is faced with a new
coat that it has not seen before.
coat that it has not seen before.

Sleeping Sickness
Sleeping Sickness
 As a result of the
As a result of the sequential
sequential coat-switching, the
coat-switching, the
immune system becomes chronically over-
immune system becomes chronically over-
stimulated and begins to attack the host’s body.
stimulated and begins to attack the host’s body.
 The overstimulation of the immune system and
The overstimulation of the immune system and
the movement of parasites into the central
the movement of parasites into the central
nervous, where they escape the immune system
nervous, where they escape the immune system
altogether, eventually kills the patient.
altogether, eventually kills the patient.

Lecture3 medical important the Protozoa.ppt

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Lecture3 medical important the Protozoa.ppt