Test 3 - Trypanosomes Stymies Flashcards
Trypanosomes Stymies is a __(single/multiple)__-celled __(prokaryote/eukaryote)__.
single; eukaryote.
Trypanosomes are like Plasmodium in that it…
∆ surface coat (antigen) weekly to hide from macrophage.
Carcinogenic medicine used to treat Trypanosome in livestock is called ____.
Ismetamidium chloride.
What is TLF? What animals in which place has it?
TLF is Trypanosome Lytic Factor. Innate immunity in primates in the Old World.
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)__.
(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.
The ligand to Trypanosome is…
Hb-Hpr complex
Trypanolytic Pore-forming protein has 3 parts:
- N-terminal, which contains a signal
- Pore-forming domain
- C-terminal
What is the significance of the C-termianl of the Tyrpanolytic Pore-forming protein/apoL-I?
Paraste with immunity binds to prevent working of apoL-I.
THF is found in..
HDL cholesterol.
How does TLF work to kill Trypanosome?
- TLF’s Hpr-Hb acts as ligand to Parasite.
- TLF is engulfed by the parasite.
- TLF is in endosome.
- Endosome with TLF merges with Parasitic Lysosome.
- – pH activates TLF’s apoL-I. apoL-I pore forming protein separates to stick to lysosome wall and puts holes in lysosome.
- H+ from lysosome enters cell cytosol proper and disrupts ionic balance.
- Cell swells and bursts through osmotic action.
SRA protein stands for __1__. Its function is to provide __2__. It works by __3__.
- Serum Resistance Associated protein.
- Provide trypanosome resistance against apoL-I.
- Binding to C-terminus of human apoL-I.
Chimpanzees, humans’ closest relatives, (do/don’t) have TLF. This is because __1__.
Do
1. Negative effect on chimps that caused selective pressure against TLF.
There are __a__ points in evolution where TLF was selected for. One group of TLF includes species including __b__. The other, __c__.
a. 2
b. humans and gorillas
c. baboons.
How is baboon apoL-I is different from human apoL-I? Why does this diference make sense?
C-terminal mutations. C-domain is where SRA protein attaches.
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?
Create transgenic mice with baboon apoL-I with promotor–b apoL-I DNA–5’ Poly A Tail.
Mice 100% resistant to Trypanosome.
Baboon apoL-I v. Human apoL-I: Creating Trypanosome-resistant human apoL-I can include (1) or (2)
- creating chimera with baboon C-terminal
2. mutating human C-terminal.
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?
Arginine –> Lysine. Mimicked in pygmies.
Baboon apoL-I v. Human apoL-I: How did scientists prove that human mut apoL-I protected against Trypanosomes?
Human mutant apoL-I Plasmid delivery. Hypotonic shock (by injection) causes cells to burst and plasmids to be inside the mouse cells.
What are negative effects of human THF?
Some African Human apoL-I (G1/GF homozygous) causes fatal kidney disease by age 30 - 40.
What are negative effects of baboon THF?
None.
Trypanosomes exist only in Africa. (T/F)
False.
Trypanosomes are transmitted by …
- Tutsi fly in Africa
2. Tabanid fly in America
The regular pathway of TLF being taken up by Trypanosome can be stopped at point where __1__ by using __2__.
- Endosome merges with Lysosome
2. NH4Cl
The transmission of Typanosome is different from that of Plasmodium because __1__. Why?
- 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.
