25 Protozoa Flashcards
how can parasites survive in the host
Hiding away
immune modulation
molecular mimicry
keeping one step ahead
how do parasites ‘hide away’
e.g. inside other cells or in tissues with little protection
how do parasites create immune modulation
e.g. by secretion of cytokine-like molecules
how do parasites create molecular mimicry
e.g. making coats or individual proteins look like host
how do parasites ‘keep one step ahead’
e.g. by constantly switching identity of surface proteins
when can parasites be transferred by insects
At micrometers size can start to see RBC – this small can be transmitted by flying insects e.g. mosquitos
Plasmodium falciparum are so small can get inside RBC and multiply
how do small, single celled parasites differ when interacting with host immune system
- different survival strategies
- can do anything larger parasites cannot e.g. grow to large numbers inside a cell
what are protozoan parasites like
small (unicellular) and non-photosynthetic that isn’t a fungus (or fungus-looking)
what are the 2 protozoan phyla in particular important for human parasitology
Apicomplexa Euglenozoa (including Kinetoplastida)
effect of protozoan parasites on killing
Combined, protozoan parasites are responsible for ~1 million deaths each year, and >300 million people are at risk of being infected
what are the Kinetoplastid cells
leishmanias and trypanosomes
how are Kinetoplastid cells defined
presence of mitochondrial DNA in the kinetoplast organism
how do Kinetoplastid cells move
Has a single flagellum – swimming and motility
what can causes Leishmaniasis
more than 20 different species of the genus Leishmania
what leads to Leishmaniasis disease
following sand sly bite, incubation period from days to one year
how do Leishmaniasis diseases heal
diseases span self-healing cutaneous to a frequently fatal visceral form
what effects the clinical manifestations of Leishmaniasis
infections Leishmania species but also on host factors
what is cutaneous leishmaniasis
L. major or L. tropica
what is mucocutaneous leishmaniasis caused by
L. (Viannia) braziliensis or L. (Viannia) guyanensis
where does Mucocutaneous leishmaniasis infect
Ulcers of the skin, mouth and nose
where does Cutaneous leishmaniasis infect
skin ulcers at the site of bite (with amastigotes in it), which can heal or complicate
what causes Visceral leishmaniasis
L. chagasi
what does Visceral leishmaniasis cause
fever progressing to anemia, wasting, enlarged liver and spleen, bleeding and breathing difficulty. Death within 6-12 months
who gets PKDL
patients with visceral disease; likely to arise from persister-type parasites
what is the sandfly life cycle
- extracellular: promastigote in the sand fly vector
- sand fly delivers growth-arrested metacyclic promastigotes
- intracellular amastigotes in the mammalian host
- sand fly takes up amastigotes in bloodmeal
what is the mechanism of host cell invasion by Leishmania
Once in host
- favourite host cell is macrophage
Can overcome complement
phagocytosis – engulf body – exactly what leishmania wants
how does Leishmania overcome complement
- Lipohosphoglycan
- Major Surface Protease (MSP/Gp63)
- CR3-C3bi-Gp63 and other interactions, facilitate phagocytic entry
how does LPG overcome complement
LPG prevents killing by MAC
how does MSP/Gp63 overcome complement
cleaves C3b to C3bi – inhibits MAC
what happens if the macrophage receptor recognises ligand
triggers a cascade that leads to phagocytosis – engulf body – exactly what leishmania wants
what do promastigotes differentiate into
replicative amastigotes. These tolerate low pH and are resistant to acid hydrolases (need no major modifications to phagosome to survive
what happens after phagocytosis
secreted LPS inhibits vATPase recruitment and lysosomal fusion
how are the sand fly infections transmitted
all-natural infections are initiated by the bite of the infected female sand flies
what does the saliva contain in a sand fly
vasodilators and parasite chemotactic factors
what do sand fly co-transmit
bacteria and viruses
what is the skin like
immunologically active organ
what happens at the skin when sand fly bites
immune cells present or rapidly recruited
bite injury initiates wound-healing and inflammatory responses
what does sand fly increases
migration of inflammatory cells to the bite site, enhancing interaction of Leishmania with host cells
what do the neutrophils do in innate immune cells
- neutrophils are first to arrive
- neutrophils are professional phagocytes – kill obligatory intracellular pathogens via ROS or NET
Leishmania and NET
most Leishmania species escape NET
what is on the Leishmania cell surface that inhibits lysosome fusion to phagosome
LPG and phosphatases
what do LPG and phosphatases
blocking respiratory burst and superoxide anion production in neutrophils
what do leishmania-infected neutrophils secrete
C-C chemokine ligand 3 (MIP-1)
C-C chemokine ligand 2
what is the effect of the leishmania infection
recruitment of DC to site of infection
what do leishmania-infected neutrophils express
apoptotic markers (promastigotes can delay or accelerate neutrophil apoptosis to their advantage)
what is the effect of C-C chemokine ligand 3 (MIP-1)
promote phagocytosis by DC
what is the effect of C-C chemokine ligand 2
recruitment of monocytes from the blood
what do monocytes differentiate into - leishmania-infected neutrophils secrete C-C chemokine ligand 2
DC, migrate to lymph nodes, and promote differentiation of TH1 cells by producing IL-1
involvement of innate immune cells - leishmania-infected neutrophils secrete C-C chemokine ligand 2
- TH1 migrate to infection site
- parasite elimination via NO production and/or enhanced ROS by macrophages
what do MO and DC engulfed promastigotes do
activate their TLR9 signalling and produce IL-12 (pro-inflammatory cytokine)
what do IL-12 do
primes naïve T cells to Th1 response
induces NK and CD4+ and CD8+ T cells to produce of IFN-gamma (key cytokine to host protection)
what does IFN-gamma activate
MO to kill intracellular parasite
what does IFN-gamma block
IL-10 production (anti-inflammatory cytokine)
what does IFN-gamma inhibit
expansion of CD4+ Th2 cells
why is IL-10 important
regulator of immunity in leishmaniasis
what does IL-10 do in immunity in leishmaniasis
protecting against leishmania causes hyper inflammation (activation of inflammasome, dead cells, pro-inflammatory cytokines etc)
what does IL-10 down regulate
Th1 cells
what does IL-10 inhibit
IL-2, TNF and MO activation of T cells
what does the anti-inflammatory role of IL-10 help
progression and chronicity
what can Leishmania enhance
disease by dampening immune response
what are the protective and pathological anti-Leishmania immune response
Same cell types have been associated with either host protection or disease progression (depending on parasite species and host genetic background)
where are monocytes and neutrophils recruited
monocytes and neutrophils rapidly recruited to infection site, where they clear parasites via ROS and NET
where do DC migrate
migrate to lymph node where they activate and polarise T cells
what does IFN-gamma and TNF activate
infected MO to kill intracellular parasites via NO
what does TH2 and TH17 do
promote infection control and resolution
what does subsequent development of IL-10 do
producing cells dampen the immune response, avoiding development of chronic infection
what does excessive recruitment of monocytes cause
hyper-inflammation
what does disproportionate Th17 response induces
tissue destruction
what does exaggerated IFN-gamma and TNF production cause
tissue destruction
what do cytotoxic granzymes and perforin by CD8+ promote
parasite dissemination
what does excessive Th2 promotes
parasite persistence and chronic infection
how is african trypanosomes and sleeping sickness transmitted
tsetse fly
African trypanosomes - Trypanosoma brucei infect
many mammals, NOT humans, disease of livestock. Game animals seem able to control parasitaemia and tolerate infection with few symptoms
African trypanosomes - what is T. b. rhodesiense indistinguishable from
indistinguishable from brucei except infects humans
Endemic in most east and southern African countries = Zoonosis
what is T. b. rhodesiense
Acute human disease that kills in few weeks/months
African trypanosomes - what does T. b. gambiense infect
mostly humans and some domestic animals. Chronic human disease that can last months/years. Endemic of most west and central African countries = specialist of humans
in Human African trypanosomiasis (HAT) Early stage (stage I) where are parasites infecting
tissue fluids surrounding the fly bite site, enter bloodstream
in Human African trypanosomiasis (HAT) Early stage (stage I) where are parasites proliferating
circulation in bloodstream and tissue fluids
in Human African trypanosomiasis (HAT) Early stage (stage I) where are parasites causing
- Fever, severe headache, muscle pain
- As disease progresses in lymph and blood: anaemia due to autoagglutination of RBC and haemolysis cardiovascular, endocrine and kidney disorders
in Human African trypanosomiasis (HAT) late stage (stage II) where are parasites infecting
invade central nervous system (CNS)
capillaries around the brain, from where they cross the blood-brain barrier
in Human African trypanosomiasis (HAT) late stage (stage II) where are parasites causes
- Invasion of the CNS and resultant inflammation
- Sleep disturbances, alteration of mental state
- Altered gait and reflexes, neurological and motor changes, lethargy, coma and death
what is on the Trypanosoma brucei cell surface
bloodstream-form trypanosome is covered in coat of variant surface glycoprotein (VSG)
what is VSG molecule
homodimer
where is VSG molecule
anchored to surface by GPI (glycosyl phosphatidyl inositol)
what clears VSG
Fast and focal endocytosis clears VSG-bound host AB
what causes VSG coat change
Period switching of VSG coat = antigenic variation
- periodic change in immunological ‘identity’
- switching of VSG coat
Antigenic variation in T. brucei - what surrounds it
dense coat of VSG completely enshrouds the parasite
how is T. brucei shielded from AB
Invariant surface molecules
how many antigens in antigenic variation in T.brucei are expressed at once
A vast repertoire of antigens to switch to/from; only 1 ever expressed at any one time
