Week 3 - Protozoan Parasites

Question 1

What is the typical length of an adult ‘Taenia solium’?

Answer 1

~3m

10^0 m

Question 2

What is the typical length of an adult ‘Ascaris lumbricoides’?

Answer 2

~25cm

10^-1 m

Question 3

What are the typical lengths of an adult ‘Necator americanus’ and ‘Schistosoma mansoni’?

Answer 3

N. americanus = ~1cm
S. mansoni = ~1.5cm
(10^-2 m)

Question 4

What is the typical length of an adult ‘Caenorhabditis elegans’?

Answer 4

~1mm

10^-3 m

Question 5

What is the typical length of an adult ‘Wuchereria bancrofti’?

Answer 5

Microfilaral stage = ~250μm

10^-4 m

Question 6

What is the typical length of an adult ‘Trypanasoma brucei’?

Answer 6

~20μm

10^-5 m

Question 7

What is the typical length of ‘Plasmodium falciparum’?

Answer 7

~2μm

10^-6 m

Question 8

What advantages does being small provide?

Answer 8

Entry into the host can be easier
Parasite may be more tied to the host’s biology
The parasite can hide from the immune response
The organisms divides faster

Question 9

What are the disadvantages of being small?

Answer 9

They have reduced motility and rely more on a vector
They are more likely to be phagocytosed
They are more tied to the host’s biology

Question 10

What does the name ‘proto-zoa’ literally mean?

Answer 10

It means ‘first animals’

Question 11

What is a rough definition of Protozoa?

Answer 11

Anything small (unicellular) and non-photosynthetic that isn’t a fungus (or fungus-looking).

It is not a natural (true) evolutionary group, they are paraphyletic. Some are closely related to animals, others are very distant.

Question 12

How many important protozoan phyla are there?

Answer 12

There are 2 protozoan phyla that are important for human parasitology.

APICOMPLEXA
EUGLENOZOA (including Kinetoplastida)

Question 13

Name some of the major protozoan pathogens of humans.

Answer 13

Plasmodium, Toxoplasma, Leishmania, American and African Typanosomes, Giardia, Trichomonas, Entamoeba.

Question 14

Describe the phylum Apicomplexa.

Answer 14

Apicomplexan organisms possess a combination of structures known as an APICAL COMPLEX. They are all parasitic and all have a single type of nucleus and no cilia or flagella. They are protozoan. Contains more than 5000 species.

There are two classes-

CONOIDASIDA (gregarines and coccidians)

ACONOIDASIDA (malarial parasites and piroplasms)

Question 15

What similarities do Apicomplexan organisms share?

Answer 15

They derive from a common ancestor.
They all infect a cell
They then differentiate to form a different type of cell.

Question 16

Which Apicomplexan organism is useful for scientific research.

Answer 16

Toxoplasma
It is easily cultivated in the laboratory.
Has excellent models for human disease.
It’s genetic crosses are feasible (in cats).
It has outstanding ultra-strucutural resolution.
The complete genome sequence is known.

Question 17

Are apicomplexans ‘obligate intracellular parasites’?

Answer 17

All apicomplexans are obligate intracellular parasites.
This means they live within host cells and they establish a unique compartment -‘parasitophorus vacuole’.
This is key to mediate communication with the host cell.

Toxoplasma has a complete set of the eukaryotic organelles. This includes two endosymbiotic organelles (mitochondrion, plastid).

Question 18

What is the ‘apical complex’?

Answer 18

The apical complex is the definitive cell structure of the phylum Apicomplexa. It is key in host cell penetration and the the establishment of intracellular parasitism.

The apical complex consists of a set of spirally arranged microtubules (the conoid), a secretory body (the rhoptry) and one of more polar rings.

Question 19

What is the ‘apicoplast’?

Answer 19

The apicoplast is a specific organelle that is a remnant of a photosynthetic past.

It is bound by four membranes, has a 35kB genomes and is considered a left-over plastid from a cyanobacterium. It is essential for parasite survival. It can therefore be a target for chemotherapy.

Question 20

What is the World’s most significant human parasitic disease?

Answer 20

Malaria
220 million cases
0.7-1.2 million deaths

Question 21

What transmits Malaria?

Answer 21

Malaria is transmitted by the female Anopheles mosquito (definitive host).

Question 22

How many species of Plasmodium cause human malaria?

Answer 22

5/6 species of the genus ‘Plasmodium’ cause human malaria.

P. falciparum, P. vivax, P. malariae, P. knowlesi,

P. ovale (actually 2 species: P.o. curtisi and P.o. wallikeri).

Question 23

How long ago did Plasmodium evolve?

Answer 23

Plasmodium evolved ~130 million years ago. They are significant parasites of birds, reptiles, rodents and primates.

Question 24

Describe the Lifecycle of Plasmodium.

Answer 24

1. When a female ‘Anopheles’ mosquito penetrates human skin to obtain a blood meal, it injects saliva mixed with an anticoagulant.
2. If the mosquito is infected with ‘Plasmodium’, it will also inject elongated sporozoites (motile, spindle-shaped asexual cells) into the bloodstream of its victim.
3. The sporozoites travel to the liver where they enter liver cells and rapidly divide asexually. A schizont is formed - this asexual division, which is called schizogony, generates the next life cycle form, called merozoites.
4. The shizont ruptures and the merozoites are released. They invade other liver cells and enter the host’s bloodstream, where they invade erythrocytes.
5. Once inside the erythrocyte, the merozoite begins to enlarge as a uninucleate cell termed a ring trophozoite. The trophozoite’s nucleus then divides asexually to produce a schizont which contains several nuclei.
6. The schizont then divides and produces mononucleated merozoites.
7. The erythrocyte ruptures and releases toxins throughout the body of the host, bringing about the well known cycle of fever and chills that is characteristic of malaria.
8. Plasmodium enters a sexual phase when some merozoites in the erythrocytes develop into gametocytes, cells capable of producing both male and female gametes - mircrogametocytes and macrogametocytes. Erythrocytes containing gametocytes do not rupture.
9. Gametocytes are incapable of producing gametes within their human host and do so only when they are extracted from an infected human host by a mosquito.
10. Within the gut of the mosquito, the gametocytes form male and female gametes.
11. The resulting diploid zygotes develop within the mosquito’s intestinal walls and ultimately differentiate into oocysts.
12. Within the oocysts, repeated mitotic divisions take place, producing large numbers of sporozoites.
13. The oocyst ruptures releasing the sporozoites. These sporozoites migrate to the salivary glands of the mosquito, and from there are injected by the mosquito into the bloodstream of a human, thus starting the life cycle of the parasite again.

Question 25

What organ do sporozoites specifically target?

Answer 25

Sporozoites selectively target the LIVER.

Question 26

Why do sporozoites selectively target the liver?

Answer 26

Sporozoites selectively target the liver through a receptor-ligand process.

Hepatocytes have specific proeoglycans on their surface:

• heparin sulphate proteoglycans have unusually high degree of sulphation.
• these ligands are recognised by sporozoites.

Question 27

What does CSP stand for?

Answer 27

CSP = Circumsporozoite protein

Question 28

What is CSP?

Answer 28

CSP = Circumsporozoite protein
It is a highly abundant protein in sporozoite.
It is anchored to the surface by a GPI (glycosyl phosphatidyl inositol) anchor. It has a low-complexity repeat region.

TSR (Thrombospondin type 1 region) is the domain involved in cell adhesion.

Question 29

How is CSP cleaved?

Answer 29

CSP is proteolytically cleaved by cysteine protease.

Cleavage occurs in Region 1
Cleavage is triggered when parasites contact liver cells.
Cleavage triggers cell invasion.

Question 30

What does CSP cleavage trigger?

Answer 30

The cleavage of the CSP protein in sporozoites triggers cell invasion.

Question 31

What does blocking Peptidase on the sporozoite’s surface achieve?

Answer 31

Blocking cysteine peptidase activity blocks cells invasion.

Question 32

Describe the Erythrocytic Cycle of the malarial parasite.

Answer 32

1. Once a liver schizont has matured, it ruptures spilling the merozoites into the bloodstream.
2. Within 1-2 minutes, each merozoite has invaded an erythrocyte. Once in the erythrocyte, the merozoite consumes haemoglobin for energy.
3. After this point it becomes known as a trophozoite.It uses this energy to form schizonts and begin another round of asexual amplification, producing up to 36 merozoites per schizont.
4. When this schizont ruptures, the merozoites are released into the bloodstream once again and infect other RBC.
5. This cycle of infection, multiplication and bursting continues until is is controlled by the immune system or antimalarial drugs.
6. These erythrocytic merozoites are responsible for the clinical manifestations of malaria.

Question 33

What is ‘Paroxysm’?

Answer 33

Paroxysm is the sudden outbreak of disease symptoms.

The synchrony of erythrocytic cycles has direct consequence for host.
The lysis of RBC by Plasmodium causes fever.
Cycles of fever are different for different Plasmodium species.
Between fevers, patient often feels well.

Question 34

What two fevers can be caused by the Plasmodium parasites?

Answer 34

Three-day intervals - Quartan Fever

Two-day intervals - Tertian Fever

Question 35

What fever intervals are caused by ‘P. malariae’?

Answer 35

‘P. malariae’ causes a quartan fever, at three-day intervals.

Question 36

What fever intervals are caused by ‘P. falciparum’ and ‘P. vivax’?

Answer 36

‘P. falciparum’ and ‘P. vivax’ both cause tertian fevers, at two-day intervals.

Question 37

Describe the process of ‘Schizogony’.

Answer 37

Schizogony is nuclear division that begins at the schizont stage.

6-40 nuclei are produced.

The erythrocyte ruptures releasing merozoites.

The subsequent blood stage results in the disease symptoms.

Question 38

Describe the process of ‘Gametocytogenesis’.

Answer 38

Gametocytogenesis is an alternative to asexual replication.

A gametocyte is a cell that specialises in the transition between the human and mosquito host.

It is an infective stage for the mosquito. To proceed from the ring stage to the gametocytes takes ~10 days in ‘Pf’.

This allows for sexual dimorphism to microgametocytes and macrogametocytes.

Question 39

Where does ‘Gametogenesis’ occur?

Answer 39

It occurs in the mosquito gut.

Question 40

In Gametogenesis what is the fate of the male gametocyte?

Answer 40

The male gametocyte undergoes dramatic ‘exflagellation’.

3x nuclear replication.
8 microgametes are formed.

Question 41

What environmental conditions trigger Gametogenesis?

Answer 41

Fall in temperature by 2-3C.
Rise in pH of 8-8.3
Fall in CO2

Question 42

Describe the process of ‘Sporogyny’.

Answer 42

A few of the blood-stage merozoites do not develop into schizonts. Instead they differentiate not male and female gametocytes.

These can be ingested by a mosquito during a blood meal.

Fertilisation occurs in the mosquito’s stomach, producing zygotes from the fusion of micro- and macrogametes.

The zygotes develop into motile, elongated ookinetes (takes ~24 hours). These penetrate the mosquito’s mid-gut wall (between epithelium and basal lamina) and mature into oocysts.

The oocysts grow, divide and rupture. Sporozoites are released which migrate through the haemocoel and travel to the mosquito’s salivary glands. The infection cycle can then repeat when the mosquito feeds on another human host.

Question 43

s

Answer 43

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