Test 3 - Trypanosomes Stymies

Question 1

Trypanosomes Stymies is a __(single/multiple)__-celled __(prokaryote/eukaryote)__.

Answer 1

single; eukaryote.

Question 2

Trypanosomes are like Plasmodium in that it…

Answer 2

∆ surface coat (antigen) weekly to hide from macrophage.

Question 3

Carcinogenic medicine used to treat Trypanosome in livestock is called ____.

Answer 3

Ismetamidium chloride.

Question 4

What is TLF? What animals in which place has it?

Answer 4

TLF is Trypanosome Lytic Factor. Innate immunity in primates in the Old World.

Question 5

TLF utilizes an inborn mechanism that binds to Hb called __(a)__, which is useful because it __(b)__. In primates, THF includes a “Trojan Horse” or __(c)__.

Answer 5

(a) Hpr, or Haptoglobin-related Protein, which binds to Hb (toxic because of Fe) to be cleared by macrophages.
(b) Trypanosomes also need heme (it is auxotrophic).
(c) Trypanolytic Pore-forming Protein, or apoL-I.

Question 6

The ligand to Trypanosome is…

Answer 6

Hb-Hpr complex

Question 7

Trypanolytic Pore-forming protein has 3 parts:

Answer 7

1. N-terminal, which contains a signal
2. Pore-forming domain
3. C-terminal

Question 8

What is the significance of the C-termianl of the Tyrpanolytic Pore-forming protein/apoL-I?

Answer 8

Paraste with immunity binds to prevent working of apoL-I.

Question 9

THF is found in..

Answer 9

HDL cholesterol.

Question 10

How does TLF work to kill Trypanosome?

Answer 10

1. TLF’s Hpr-Hb acts as ligand to Parasite.
2. TLF is engulfed by the parasite.
3. TLF is in endosome.
4. Endosome with TLF merges with Parasitic Lysosome.
5. – pH activates TLF’s apoL-I. apoL-I pore forming protein separates to stick to lysosome wall and puts holes in lysosome.
6. H+ from lysosome enters cell cytosol proper and disrupts ionic balance.
7. Cell swells and bursts through osmotic action.

Question 11

SRA protein stands for __1__. Its function is to provide __2__. It works by __3__.

Answer 11

1. Serum Resistance Associated protein.
2. Provide trypanosome resistance against apoL-I.
3. Binding to C-terminus of human apoL-I.

Question 12

Chimpanzees, humans’ closest relatives, (do/don’t) have TLF. This is because __1__.

Answer 12

Do

1. Negative effect on chimps that caused selective pressure against TLF.

Question 13

There are __a__ points in evolution where TLF was selected for. One group of TLF includes species including __b__. The other, __c__.

Answer 13

a. 2
b. humans and gorillas
c. baboons.

Question 14

How is baboon apoL-I is different from human apoL-I? Why does this diference make sense?

Answer 14

C-terminal mutations. C-domain is where SRA protein attaches.

Question 15

Baboon apoL-I v. Human apoL-I: Experiment 1: How did scientists prove that B apoL-I kills parasites? What was the result of the experiment?

Answer 15

Create transgenic mice with baboon apoL-I with promotor–b apoL-I DNA–5’ Poly A Tail.
Mice 100% resistant to Trypanosome.

Question 16

Baboon apoL-I v. Human apoL-I: Creating Trypanosome-resistant human apoL-I can include (1) or (2)

Answer 16

1. creating chimera with baboon C-terminal

2. mutating human C-terminal.

Question 17

Baboon apoL-I v. Human apoL-I: Mutating human apoL-I C-terminal: What was the specific mutation (AA to AA)? Where is this seen in nature?

Answer 17

Arginine –> Lysine. Mimicked in pygmies.

Question 18

Baboon apoL-I v. Human apoL-I: How did scientists prove that human mut apoL-I protected against Trypanosomes?

Answer 18

Human mutant apoL-I Plasmid delivery. Hypotonic shock (by injection) causes cells to burst and plasmids to be inside the mouse cells.

Question 19

What are negative effects of human THF?

Answer 19

Some African Human apoL-I (G1/GF homozygous) causes fatal kidney disease by age 30 - 40.

Question 20

What are negative effects of baboon THF?

Answer 20

None.

Question 21

Trypanosomes exist only in Africa. (T/F)

Answer 21

False.

Question 22

Trypanosomes are transmitted by …

Answer 22

1. Tutsi fly in Africa

2. Tabanid fly in America

Question 23

The regular pathway of TLF being taken up by Trypanosome can be stopped at point where __1__ by using __2__.

Answer 23

1. Endosome merges with Lysosome

2. NH4Cl

Question 24

The transmission of Typanosome is different from that of Plasmodium because __1__. Why?

Answer 24

1. Not vector species-specific (mosquitos only verses tutsi and tabanid)
   Because there is no life cycle within the tabanid– “flying syringe” regurgitates infected blood right back up.

Question 25

Transgenic Cattle production done by…

Answer 25

Taking (2n) with transgenic elements and inserting into donor egg (n) (enucleated).

Question 26

Transgenic Cattle is just a male because… (2 reasons)

Answer 26

1. Artificial Insemination.

2. Heterozygous good, homozygous bad.

Question 27

What are some bacterias that live in lysosome? Where do they live? (2)

Answer 27

1. TB in endosome by arresting early endosome

2. Sarmonella grwos in lysosome.

Question 28

Leishmania is similar to Trypanosome. It is taken up by the human macrophage and grows in host lysosome. Would TLF be able to kill it? Why?

Answer 28

No, because human immunity protein does not let apoL-I to push holes its own lysosome.