Protozoa, Trypanosoma, & Antigenic Variation Flashcards
(107 cards)
1
Q
What is the kinetoplast, where is it found, and what function does it have?
A
what - disk of interlocking DNA circles (kDNA) where - along inner surface in mitochondria function - mitochondrial transformation between life cycle forms
2
Q
What are the 2 components of kDNA and how are they arranged?
A
- maxi-circles: ~50 copies
- mini-copies: 5000-10000 copies
arrangement - concatenated mass of interconnected complex networks
3
Q
What is a basal body and where is it found?
A
what - anchors flagellum
where - outer surface of mitochondrial membrane
always close to kinetoplast
4
Q
What are the 3 major kinetoplastid infections in humans?
A
- human African Trypanosomiasis (HAT)
- Chagas’ disease
- Leishmaniasis
5
Q
What 4 morphological forms can occur in the various kinetoplastid life cycles?
A
- amastigote - no flagellum
- promastigote - flagellum, in vector
- epimastigote - undulating membrane
- trypomastigote
6
Q
What is the function of the glycosome?
A
glycolysis
7
Q
How do the functions of the glycosome and mitochondrion change as the parasite switches between hosts?
A
mammals - environment is rich in glucose so ATP only through glycolysis
mitochondria repressed
lacks components of CAC & ETC
no oxidative phosphorylation
insects - low glucose so mitochondria is activated
glycosomes decrease enzymes
8
Q
Does the amastigote have a flagellum?
A
no
9
Q
Does the amastigote have a nucleus?
A
yes
10
Q
Does the promastigote have a flagellum?
A
yes
11
Q
Does the promastigote have an undulating membrane?
A
no
12
Q
Where is the promastigote found?
A
insect vector
13
Q
Are the kinetoplast/basal body anterior or posterior to the nucleus in the promastigote?
A
kinetoplast/basal body at anterior end in front of nucleus
14
Q
Does the epimastigote have a flagellum?
A
yes
15
Q
Does the epimastigote have an undulating membrane?
A
yes
16
Q
Are the kinetoplast/basal body anterior or posterior to the nucleus in the epimastigote?
A
kinetoplast/basal body at anterior end in front of nucleus
17
Q
Does the trypomastigote have a flagellum?
A
yes
18
Q
Does the trypomastigote have an undulating membrane
A
yes
19
Q
Are the kinetoplast/basal body anterior or posterior to the nucleus in the trypomastigote?
A
posterior to nucleus
20
Q
What are the 4 basic types of trypomastigote?
A
- long and slender - mammals
- stumpy - in mammal, infective to host
- procyclic - insect
- metacyclic - in insect, infective to mammal
21
Q
Into what 2 sections is the genus Trypanosoma divided?
A
- Salivaria
2. Stercoraria
22
Q
Section Salivaria is also known as
A
Anterior Station Development
23
Q
Species in Salivaria develop in what part of the vector?
A
anterior
24
Q
Section Stercoraria is also known as
A
Posterior (Hindgut) Station Development
25
Species in Stercoraria develop in what part of the vector?
posterior/hindgut
26
Trypansosoma brucei is found in which section?
salivaria
27
What is the vector for Trypansosoma brucei?
Glossina - Tsete fly
28
What stage of Trypansosoma brucei is infective to humans?
metacyclic
29
What stage of Trypansosoma brucei lives in the blood of humans?
slender tryps
30
Where do the tryps multiply?
Slender Tryps: Body Fluids
Stumpy Tryps: Do not multiply
Procyclic Tryps: Fly's gut
Epimastogotes: Salivary Gland
31
What does the posterior end of Trypansosoma brucei look like?
blunt
32
What stage of Trypansosoma brucei si infective to Glossina?
metacylci tryps
33
How many subpsecies of T. brucei are there?
3
34
How can the subspecies of Trypansosoma brucei be differentiated?
DH
pathology
morphologically identical
35
What is the common name of Glossina? What does that name mean?
Tsetse
| "fly distructive to cattle"
36
How can Glossina be identified?
"meat cleaver" cell in wing
37
Where in Africa is Glossina most prevalent?
tropical Africa
| between 15 deg N & 15 deg S = fly belt
38
What disease is caused by T. brucei brucei?
Nagana
39
What animals are infected with Nagana?
antelope & livestock
40
What 2 subspecies of T. brucei cause African Sleeping Sickness in humans?
1) T. brucei rhodesiense (Tbr) - East African Sleeping Sickness
2) T. b. gambiense (Tbg) - West African Sleeping Sickness
41
What are the differences in Tbr & Tbg morphology?
identical
42
What are the geographical distributions of Tbg & Tbr?
Tbr - Eastern/Southeastern African
| Tbg - West and Central Africa
43
Does Tbg or Tbr infect native game reservoir hosts?
Tbr infects cattle and antelope
44
Does Tbg or Tbr cause most cases of sleeping sickness?
Tbg
45
What are the 2 stages of human African trypanosomiasis?
1. hemolymphatic - parasite is found in the peripheral circulation and lymph system, entering tissue fluid, but does not invade the CNS
2. meningo-encephalitic - parasite crosses BB and enters CNS
46
What happens in either stage of human African trypanosomiasis if it is not treated?
Death within a few months (Tbr) to 3 years (Tbg)
47
What if the rate of disease progression in Tbr
death within a few months
| Rapidly invades the parasite and invades the CNS
48
What is a chancre?
sore at bite site
49
What is the rate of disease progression in Tbg?
death within 3 yrs
| more slow
50
What symptoms can occur in each stage of human African trypanosomiasis?
Mild symptoms occur early on - fever, headaches, muscle & joint aches
In later stages (1-2 yrs), there is an evidence of CNS involvement (personality change, tend to suffer from daytime sleepiness, nighttime sleep disturbance, paralysis, and problems with balance/walking)
51
What is Winterbottom's sign?
swollen lymph nodes at base of neck
52
In which subspecies is the parasite load in the blood higher?
Tbr
53
Why is serological testing used only to detect Tbg infections?
Lower parasite load means that one would need to use the antibodies to detect the parasite
54
Why must cerebrospinal fluid be examined in all sleeping sickness infections?
to see involvement in CNS in infection
55
Who should receive treatment for sleeping sickness?
everyone
56
What factors will determine which drug should be used?
1. type of infection (Tbr or Tbg)
| 2. disease stage
57
What are the 4 drugs which can be used to treat sleeping sickness?
1. pentamidine
2. suramin
3. melarsopral - Mel B
4. eflorinithine
58
Does pentamidine cross the BBB?
no
59
Against which stage is pentamidine effective?
1st stage of Tbg
| inhibits DNA & RNA synthesis
60
Is pentamidine used to treat Tbg, Tbr, or both?
Tbg
61
Does surmain cross the BBB?
no
62
Against which stage is surmain effective?
1st stage of Tbg & Tbr
inhibits oxidation of NADH
too much is toxic = kidney failure
63
Is surmain used to treat Tbg, Tbr, or both?
both
64
Does melarsopral cross the BBB?
yes
65
Against which stage is melarsopral effective?
```
late stage Tbr & Tbg
inactivates tyrp pyruvate kinase = inhibits ATP synthesis
arsenis based = high toxicity
seizures
1/20 die of treatment
```
66
Is melarsopral used to treat Tbg, Tbr, or both?
both
67
Does eflorinithine cross the BBB?
yes
68
Against which stage is eflorinithine effective?
late stage - "resurrection drug"
inhibits ornithine decarboxylase
cell division & differentiation
69
Is eflorinithine used to treat Tbg, Tbr, or both?
Tbg
70
What is a drawback to using melarsoprol?
high toxicity
| 1/20 die of treatment
71
Why is eflornithine known as the "resurrection drug"?
used on late stage comotose patients
72
Why & for how long do patients require follow up examinations?
serial examination of cerebrospinal fluid for 2 yrs
73
What is the main method of prevention and control of sleeping sickness?
minimized testse fly exposure
74
What type of clothing should be worn to minimize testes fly bites?
neutral colors
75
Why are tsetse flies often found inside vehicles?
motion & dust
76
What is sterile insect technique?
SIT - sterilize tsetse flies and release
| 3-4 generations w/ insecticides will eliminate local populations
77
What is antigenic variation?
altering surface proteins in order to avoid a host immune response
78
The surface coat of T.brucei blood typromastigotes consists primarily of a single protein which is know as the
VSG (variant surface glycorprotein)
79
Does the immune system recognize VSG?
yes
80
Does the immune response to VSG remove all of the parasite?
yes: <1% of tryps survive b they posses variant VSG
81
How are the waves of T.brucei infection produced?
variant forms next wave of infection after multiplying
82
What is a variant antigenic type?
Maintains chronic infection as a result of this antigenic variation of the surface coat and can last for years
83
How many genes are involved in antigenic variation?
~1000 VSG genes
84
Trypanosoma cruzi is found in which section?
Stercoraria
85
What is the vector for T.cruzi?
reduviid bugs
86
What stage of the T.cruzi parasite is infective tohumans?
Metacyclic tryps
87
How does T.cruzi enter the human?
enter blood when vector takes bloodmeal and vector defecates on skin letting in metacyclic tryps
88
What is the intracellular stage of T.cruzi?
amastigotes
89
What stage of T.cruzi is infective to the vector?
amastigotes
90
What is distinctive about the posterior end & kinetoplast of T.cruzi tryps?
very pointed posterior end
| very large kinetoplast
91
Is T.cruzi capable of antigenic variation?
no
92
How does the lack of antigenic variation affect the # of T.cruzi tryps in the blood?
very low #s of tryps in blood
93
What is a chagoma?
local inflammation at bit site
| entry of metacyclic tryps
94
What is Romana's sign?
enters eye
| edema of eyelid & conjective
95
What is a pseudocyst?
cluster of amastigotes
96
What symptoms are associated with the acute stages of T.cruzi infection?
fatigue, fever, swollen lymph nodes
if parasite spreads: muscle,intestine, blood marrow
anemia, nervous disorders, weakness, muscle pain
97
What is the common outcome of infection in children?
death in 3-4 wks
98
What organs are most commonly affected in chronic T.cruzi infections?
heart, intestinal tract, muscles
99
The amastigotes in T.cruzi produce ___ which results in loss of muscle function
neurotoxins
100
What happens in the intestinal tract during chronic T.cruzi infection?
smooth muscle peritalsis
esophagus & colon lose tone
megaesophagus & megacolon
101
What are the megaesophagus and megacolon
muscle in esophagus & colon is streched out bc of smooth muscle peritalsis
102
What happens in the heart during T.cruzi infection?
muscle contraction affected
enlarged & flabby
decreased pumping efficiency
heart failure
103
How is T.cruzi diagnosed?
1. examine tissue fluid for asmastigotes
| 2. Xenodiagnosis
104
What is xenodiagnosis?
```
lab raised vectors in suspected patient
~40 lab raised bugs feed on patient
3-4 wks: squeeze bugs to see fecal droplet
dissect hindgut
examine for parasite
```
105
How is T.cruzi infection controlled?
1. hemotherapy - Nifurtimax
| 2. vector control
106
How can T.cruzi vector be controlled?
```
plaster wells
concrete floors
metal roofs
screen doors & windows
insecticides
bed netting
```
107
What is the distribution fo T.cruzi?
Mexico, C.America, S.America: ~10 million cases
urban areas - blood transfusion
US - mainly SW
