Lecture 8 Leishmania- Leishmaniasis Flashcards
What are the three forms of leishmaniasis?
-Visceral(most serious)
-Cutaneous(most common)
-mucocutaneous
How is leishmaniasis caused?
-Through leishmania parasites that are transmitted through the bite of female phlebotomine sand flies
Does everyone who gets infected by the leishmania parasite get the disease?
No only some
What is the leishmania life cycle?
- sand fly injects promastigotes into the skin(infected stage)
- Promastigotes are phagocytized by macrophages or other types of mononuclear phagocytic cells
3.Promastigotes transforms into amastigotes - Promastigotes multiply in cells of various tissues and infect other cells
(2-4 Human stage) - sandfly ingests macrophages infected with amastigotes
- ingestion of parasitized cells
- amastigotes transform into promastigote stage in the gut
- divide in the gut and migrate to proboscis
Leishmania development within the sand fly
Amastigote–> procyclic promastigote–> nectomonad promastigote–> leptomonad promastigote–> haptemonad promastigote–> metacyclic promastigote
Leishmania cellular characteristics
- are considered as aneuploid organisms
- Differential gene expression in the different life cycle stages seems to be regulated
by sensing and integrating two major environmental clues: temperature and pH. - No functional RNAi machinery present
- They replicate by binary fission, but there are some evidences of sexual
reproduction in the flies.
Daughter with short flagellum
Daughter with long flagellum
How do promastigotes interact with non phagocytic cells?
-GIPLs and and GPI anchored glycans cover all the surfaces of the parasite
-Gp63 is the predominant surface protein of the promastigoTes
-Leishmania do not actively invade the cells but instead induces its own receptor mediated endocytosis
Promastigote interaction with phagocytic host cells
- promastigotes become predominantly phagocytosed predominantly by neutrophils
-are taken up by these cells via CR3
Immune response against leishmania
1) Mast cells collaborate in disease progression by secreting IL-
4 and IL-13 fostering Th2 responses and parasite survival
2) Neutrophils eliminate leishmanial parasites through
phagocytosis, ROS, and NETs release
Leishmania can survive transiently within neutrophils by:
- inhibiting phagolysosome biogenesis and oxidative stress
- delaying neutrophil apoptosis.
Infected neutrophils secrete IL-8 and MIP1 , which attract
additional neutrophils and other phagocytic cells, favoring
Leishmania survival and pathology
Macrophages can be differentiated in M1 or M2
during leishmaniasis.
* M1 macrophages produce proinflammatory
cytokine and chemokines, NO and ROS, booster
Th1 responses, and favor disease control.
* M2 macrophages increase the production of IL-
10 and TGF and support Th2 response and
disease progression
4) Dendritic cells (DCs) regulate immune responses against Leishmania by migrating to the
draining lymph nodes to present Leishmania-derived antigen to naïve T cells.
DCs can induce the differentiation of Th1 by secreting IL-12 and IL-27 or Th2, by blocking IL-12
secretion.
5) NK cells have a protective role in leishmaniasis by secreting IFN to boost Th1 response IL;
interleukin IFN leading to the eventual elimination of the parasite
what is the causative agent of visceral leishmaniasis?
-leishmania donovani
What is the incubation period for visceral leishmaniasis?
between 2weeks-18 months
what are some of the symptoms of visceral leishmaniasis?
-abdominal swelling
-hepamegaly and spleenomegaly
-anemia and weightless
-diarrhea and fever
-low platelet count
what is the mortality rate for VL?
Mortality rate between 75%-95% with death occurring within 2 years.
What is correlated with an asymptomatic outcome of VL?
balance of IFN-gamma and IL-10 and low cytokine levels
what is correlated with active visceral leishmania?
Inbalance of IFN-gamma and IL-10 and high levels of cytokines.
Diagnosis methods for VL
-splenic puncture
- liver puncture
-bone marrow aspiration
-ELISA(antibody detection)
-PCR
Which is the most common of the leishmaniases?
Cutaneous
Cutaneous Leishmaniasis
-relatively mild skin disease
-causative agent include L. tropic, L. major, L. aethiopica
-amastigotes are found primarily in macrophages around cutaneous sites
-sandflies must feed at these sites in order to acquire the infectious amastigotes
What is the incubation period for cutaneous leishmaniasis?
-couple months to 3 years but shorter in L. major which is in little as 2 weeks
What are the signs of infection in cutaneous leishmaniasis?
-first sign of infection are small papules
-papules are dry and ulcerate every couple months
-lesions evolve from papules(dry) to nodular plaques to ulcerative lesions with scab or crust.
What are the diagnosis methods for cutaneous leishmaniasis?
Biopsy Specimen/ Aspirates
-culture and PCR
Dermal scraping
-thin smearsH
How do patients react to cutaneous leishmaniasis?
- The anergic patient is incapable of mounting a response to infection, which therefore
can proliferate indefinitely, forming many lesions This type of disease, known as
diffuse cutaneous leishmaniasis. It is seen primarily in infections caused by L.
aethiopica and L. pifanoi. - The hypersensitive patient is capable of excellent antibody and cellular responses
but cannot completely eliminate the parasites, so as the central lesion heals, active
peripheral ones continue to form. This type is known as leishmaniasis recidiva.
Diffuse CL
Recidiva CL
Mucocutaneous leishmaniasis
- Caused by Leishmania braziliensis, L. guyanensis and L. panamensis
- Amastigotes are found in macrophages in ulcerations at mucocutaneous junctures
of the skin. - This disease is also known by various other names, including American
leishmaniasis, espundia, uta, pian bois, and chiclero ulcer. - In some parts of Brazil, such lesions are said to occur in about one fifth of cases of
the disease. - Various forest rodents and dogs are naturally infected.
- Sandflies belonging to the genera Lutzomyia and Psychodopygus are vectors.
- A clinically similar disease is seen in Ethiopia and Sudan and the causative agent is
believed to be L. tropica and possibly L. major. - Diagnosis and treatment follow the recommendations of severe cutaneous
leishmaniasis.
