Effect Leishmania Parasite Expression Mhc Classi Dendritic Cells Biology Essay
Leishmania are protozoan parasite of the household of Trypanosomatidae responsible for Leishmaniasis. These are obligate parasites that are transmitted to the mammalian being by a bite from a sand fly. In nature there are more than 700 species of sand flies of which approximately about 70 are known to be vectors of leishmaniosis ( Lane, 1993 ) . Based on were they are found, Leishmania can be divided into 2 different classs, those found in the Old universe ( Africa, Europe and Asia ) , and transmitted by sand flies of the Phlebotomine species. They comprise of L. major, L. tropica, L. infantum and L. donovani. Leishmania of the New universe ( Americas and Oceania ) are transmitted to the mammalian host by the Luzomyia sand fly, these comprise of L.mexicana, L.Amzonesis, L.Breziliens, L. chagasi and a batch more. Harmonizing to Azpura et Al ( 2010 ) , more than 20 species of Leishmania are able to do the disease, nevertheless the chief 1s are those listed above as their biological science and methods of infection have been studied.
Leishmaniasis is a disease that is caused by the Leishmania parasite and is endemic in more than 88 states worldwide ; the disease is more prevailing in hot parts i.e. the Sub-Saharan Africa, and other tropical and semitropical states. Harmonizing to the WHO, more than 12 million people are affected worldwide with another estimated of 350 1000000s being at hazard of the undertaking the disease, and this figure is lifting due to globalization and touristry, plus every bit good the addition of HIV in the recent old ages ( Donovan et al, 2007 ) .
Leishmaniasis can be subdivided into 3 different classs based on the symptoms and the parasite that cause them ; cutaneal leishmaniosis ( CL ) , mucocutaneous Leishmaniasis ( ML ) and splanchnic leishmaniosis ( VL ) .
Cutaneous Leishmaniasis is caused by L. Mexicana, L tropica and L.major, it is characterised skin lesions, these lesions are usually self healing. It is estimated that globally there are about 1 to 1.5 million instances of cutaneal Leishmania each twelvemonth ( Reithinger, 2008 ) .
The mucocuteneous leishmaniosis is characterised by debasement of mucosal membranes ; this can take to lasting disfiguration, this most noteworthy rhinal country, the throat and the oral cavity. It is caused by L. braziliensis ( Snoog, 2008 ) .
Visceral Leishmania is the most terrible signifier the disease and is caused by L. infantum, L. chagasi and L. donovani, its characterised by febrility, expansion of of import variety meats like the lien and liver later doing anemia and weight loss. This has a high mortality rate with about 6000 instances every twelvemonth ( Azpura et al 2008 ) .
Biology of Leishmania
Leishmania parasite exists in two chief morphological signifiers during its life rhythm ; the promastigote signifier and amastigote signifier.
In the vector, Leishmania is found the promastigote signifier. Under a microscope, this can be seen as a whiplike, motile with an elongated organic structure microoroganism. The promastigote signifier is found in the extracellular phase of the Leishmania life rhythm. Promastigote are infested into the blood stream when the sand fly feeds on its mammalian victim. The promastigote so undergoes alterations intracellularly into amastigote.
The amastigote signifier of the parasite is found in the intracellular phase of the parasite in the mammalian cells after injection by the sand fly. The amastigote signifier is non motile, ovoid in form and has no scourge. This is found in the intracellular phase of the parasitic life rhythm.
In the sand fly, Leishmania undergoes a development metamorphose into seven different signifiers, these are known as subgenus. Early cellular transmutations that take topographic point in vivo have non been punctually being studied, nevertheless in vitro observations have suggested that the transmutations starts with the development of amastigotes into procyclic promastigotes ( Bates, P.A. , 1994 ) , this procedure occurs between 24 to 48 hours. The procyclic promastigotes are the initial dividing signifier that increases the population of parasites in the intestine of the sand fly. Procyclic promastigotes are short with a organic structure length of 6-8µm, they have a really short scourge and are non really motile. In vivo they are found the bloodmeal of the sand fly ( Rogers, M.E. et Al, 2002 ) . Procyclic promastigotes besides produce of import surface molecules, most notably the lipophosphoglycan ( LPG ) that aid their endurance in the sand fly and besides aid their immune equivocation ( Descoteaux and Turco, 1999 ) . The importance of these LPG was shown in genetically engineered mutation L. Major which was shown to non last in the sand flies or even easy combated in the infection ( Sacks et Al, 2000 ) .
The 2nd most of import transmutation in Leishmania life rhythm is the elongation of the procyclic promastigote into a 12-20µm nectomonad promastigote. This takes topographic point 2-3 yearss after bloodfeeding from a mammalian host ( Rogers et Al, 2002 ) . Nectomonad promastigotes are really motile and travel towards the peritrophic matrix ( PM ) , this protect them against chemicals in the intestine of the sand fly ( Walters et Al, 1989 ) .
The parasite nevertheless has to get away onto the epithelial cells in the backbones of sand fly as although the PM initiates the protection of the promastigotes, their thickness can come as a hindrance to the development of the promastigotes ( Lawyer et al. , 1990 ) .
After 3-7 yearss after bloodfeeding, the nectomonad undergoes another metamorphose into leptomonads promastigotes, these have shorter organic structure length ( 8-9µm ) ( Gossage et al, 2003 ) . These leptomonads can give rise to short promastigotes known as heptomonads, these attach themselves in the midgut of the sand fly but they mechanisms are non to the full known ( Bates and Rojers, 2004 ) . The leptomonads produce a gel like substance that helps in the spread of infection ; the promastigote secretory gel ( PSG ) ( Rogers et al, 2002 ) .
Leptomonads promastigotes differentiate into the metacyclic promastigotes. This is the major distinction in the promastigotes rhythm as it is ready to infect mammalian cells. Metacyclic promastigotes are narrow with 5-8µm cell organic structure and are extremely motile, a characteristic that allows them to migrate into the lms of the midgut of the sand fly, where they can be transmitted into the blood stream when the female sand fly is bloodfeeding on a mammalian host ( Rogers et Al, 2002 ) .
These cells are non spliting cells in the sand fly, and are free swimming ready for infection, they besides present characteristics that allows them to hedge the host immune system, for illustration the complement mediation ( Sacks, 2002 ) . In the mammalian host, the metacyclic promastigote differentiates into amastigote and loses the scourge alterations shape in the mammalian cells.
Another subgenus associated with Leishmania is the Viannia subgenus. This has non been to the full studied nevertheless it is presumed that cells undergo the same processes from promastigotes to amastigotes. It can besides be said that the nectomonads in this instance make non adhere to the epithelial tissue of the vectors ; nevertheless they produce LPG like those of Leishmania subgenus ( Pinto-da-Silva et Al, 2002 ) .
Immune system and control of Leishmania
The immune system is the ensemble of the cells and chemicals that protect the person against any infection that they encounter. The unconditioned response is the first point of control for Leishmania invasion of the immune system. Their survey on Lieishmania Amazonesis, Aranha et Al ( 2003 ) explained that Natural Killer ( NK ) cells play a cardinal function in the control of Leishmania infections in the innate immune response. They found out that NK cells activated by the interleukin-2 ( IL-2 ) , lead to a decrease of feasible parasites in vitro compared to a control group that was n’t exposed to the activated NK cells. The degree of INF-? were besides elevated in the trial group, this suggests that the NK cells play a cardinal function in commanding early infection. It was found nevertheless that in cutaneal and splanchnic leishmaniosis, the control of the diseases is regulated by the activation of T cell, which induce the IL-12 goaded Th1-type immune and the production of the interferon gamma ( IFN-? ) by the CD4+T cells. The production of IFN-? is of import in battling intracellular parasites by advancing the activation of macrophage ; this produces azotic oxide which kills the parasite ( Alexander et al, 1999 ) . Controling Leishmania infection besides depends on a group of intracellular proteins known as signal transducer and activator of written text ( STATs ) . There are 7 types of STATs, these are of import in interceding the initiation of the cytokines-responsive cistrons and the ordinance of biological activity of cytokines ( Wurster et al, 2000 ) .
In the development of cell-mediated response to Leishmania, the yoke of IFN-? and STAT1 is really of import in commanding the disease. IFN-? is a type II interferon secreted by activated T cells and NK cells ; their activity depends upon the activation of STAT1 written text factors. In response to IL-12 coupled with STAT4 signalling, the IFN-? coupled with STAT1 is released bring oning the activation of macrophages by bring oning iNOS ( inducible azotic Oxide synthase ) look and the production of NO, taking to the riddance of the parasite and Leishmania infections ( Sacks and Noben-Trauth, 2002 ) . A recent survey by Barbi et Al ( 2009 ) shows that STAT1 are of import in CD4+T cells immune response in L.major infections by interceding the enlisting of T cells to the infection site. IFN-?/? with STAT2 have been shown to intercede the ordinance of innate immune response in CL with L.major, they initiate the NO and the NOS2 ( azotic oxide synthase 2 ) , shown to play a function in the protection against intracellular parasites ( Diefenbach, 1998 ) .
Immune equivocation by Leishmania
Immune equivocation in Leishmania infections is the mechanisms used by the parasite to avoid the devastation by the immune system. In infections by L.Major, it was shown that L.Major promastigotes secrets substances that inhibit the migration of murine dendritic cells ( DCs ) in vitro and that the lipophosphoglycan ( LPG ) on the surface of L.major besides inhibits the migration of langerhans cells in CL ( Ponte-Sucre et Al, 2001 ) . This has been attributed to the glycoproteins gp63 and glycoinosytolphospholipids ( GILPs ) and LPG found the surface of different strains of the parasite. This happens due to alterations that occur during DCs enlisting to the site of infection. The parasite changes the chemokine-chemokine receptor ( CCR1, CCR2, CCR5 and CCR6 ) found on the DCs and accordingly decelerating the migration procedure. Other surveies show that another mechanism used by Leishmania parasites is the suppression of DC ripening ; they do this by detaining the ripening of DC favoring the constitution of infections ( Bennett et al, 2001 ) .
On the other manus nevertheless it was that Leishmania infections depend upon their interactions with certain cytokines. It was shown that IL-4 and IL-13 with STAT6 favour the nonhealing signifiers of CL in mice ( Tripathi et al, 2007 ) . In mice, IL-4 was shown to be an inhibitor of IFN-?-producing CD4+T cells an of import mechanism in the Th1 immune response in Lieshmania infections ( Tripathi et al, 2007 ) . The mechanisms of interaction between the parasite and these cytokines is non known, nevertheless certain literatures suggest that the IL-13 and Il-4 promote parasitic endurance and continuity by triping macrophage to undergo alternate activation compared to their normal activation ( Sacks and Noben-Trauth, 2002 ) this besides prevent the development of Th1 responses. Another cytokine of import in the development of leishamania is the IL-10 associated with STAT2, these are of import in the suppression of pro-inflammatory cytokines like IL-2, IL-1 and the TNF of import in the Th-1 immune response in Leishmania. It was shown to be associated with the nonhealig signifiers of leishmaniosis bothi in animate being and human ( Tripathi et al, 2007 ) .
Another of import mechanism of immune equivocation in Leishmania infections is the downregualtion of MHC proteins on the surface of macrophages. In experiments on mice it was shown that Leishmania infection lead to low look of MHC-II on the surfaces of DCs ( Muraille et al, 2003 ) . This has been defined as a manner for the parasite to suppress the antigen presentation and besides the suppression of the T cells stimulation. However Ponte-Sucre et Al ( 2001 ) found that in langerhans cells ripening, the LPG on the surface of the L.major upregulated the look of MHC-II, but this was merely during cell ripening. The consequence of Leishmania on the look of MHC-I is non to the full understood, nevertheless it was shown that when the IFN-? bring forthing CD4+ cells is reduced, the presentation of Leishmania antigen by MHC-I is blocked ( Roger and Titus, 2004 ) .